Enzalutamide - India

On May 16, 2019 The Delhi High Court set aside the order issued by Controller & remanded the case back to patent office for fresh consideration.

The Regents of the University of California’s (Petitioner) filed Indian patent application, 9668/DELNP/2007 on Dec 13, 2007. The invention relates to ““Diarylhydantoin Compounds” & specifically claims compound Enzalutamide. On May 13, 2009, the petitioner filed a request for examination. The Controller issued the First Examination Report (FER) on May 24, 2013. Multiple Respondents filed pre-grant oppositions to said patent application. Different oral hearings with respect to different respondents were held in Jul 2015 & in Jul 2016 before Controller. The Controller passed the order on Nov 08, 2016 & rejected the patent application. Petitioner filed petition before Delhi high court.

Petitioner advanced their contentions, essentially, on three fronts.

First, it was submitted that no evidence was filed by respondent nos. 3 to 7 in support of their oppositions. Second, they contended that the petitioner had no effective opportunity to deal with the “Bohl” document. Third, they submitted that the evidence of the inventors filed by the petitioner was not considered by the Controller. In addition to the above arguments, it was also contended that the Controller had erred in applying an incorrect test for adjudicating whether there were inventive steps. As is apparent from the above, the petitioner’s challenge to the impugned order is of twofold: the first relates to the decision making process and the second relates to the merits of the decision. Thus, petitioner contended that principles of natural justice have been violated.

With respect to first contention, Court said that it is apparent from the plain reading of Section 25(1) of the Patents Act that a representation to oppose grant of a patent is required to be in writing. There is no requirement that any such opposition is to be supported by an affidavit. In terms of Rule 55(1) of the Patents Rules, the pre-grant opposition is required to be accompanied by a statement of evidence. It is not necessary that such evidence be accompanied by an affidavit. The principal object of requiring the opposition to be in writing is, plainly, to enable the Controller to examine the grounds stated therein and to provide an opportunity to the applicant to meet such opposition. In the instant case, there is no dispute that the respondents had submitted their respective representations. The Controller had issued a notice with regard to the same, thus enabling the petitioner to file a statement and evidence in support of its application. The parties were also heard. Thus, as far as this stage is concerned, there is no dispute that the principles of natural justice were complied with.

With respect to second contention, Petitioner argued that respondent no.3 had produced the “Bohl” document during the course of hearing, and the written submissions filed by respondent no.3 had further expanded the submissions made on its behalf during the course of the oral hearing. Petitioner thus contended that this was, essentially, a new argument and the petitioner had no opportunity to deal with the same. Court, however, said that although Bohl document was produced at the belated stage, it cannot be disputed that the petitioner was given full opportunity to make submissions with regard to the said document. The petitioner had not only made oral submissions with regard to the said document but had also filed written submissions at a later date. Also the consideration of the representation filed to oppose grant of patent is an intrinsic part of the decision making process whether to accept the claim and, therefore, cannot be viewed as a completely independent proceeding. Thus, the Controller cannot ignore any document or material produced, which may have a bearing on whether the patent ought to be granted. Thus the essential requirement of providing the petitioner an opportunity to deal with the said document was, thus, duly met.

But with respect to post hearing submissions, Court said that such submissions are clearly meant to record only the oral submissions made at the hearing in order to assist the decision maker & cannot expand the scope of submissions made in the oral hearing. There is no scope for entertaining additional arguments after the oral hearing is concluded. If the Controller intends to take into account any additional arguments raised after oral hearing is concluded, he is, obviously, required to put the applicant to notice regarding the same. In the impugned order Controller accepted the arguments raised by respondent no.3 after conclusion of the hearing without providing notice, & therefore cannot be sustained.

With respect to third contention, Petitioner argued that impugned order is vitiated as the Controller had failed to consider the affidavit submitted by its experts. There is no reference or discussion regarding the affidavits of the experts submitted by the petitioner in the impugned order. The respondents contended that the evidence of experts had been considered and dealt with by the Controller in the impugned order. In support of its contention, respondent no.3 had, in its written submissions, set out a tabular statement referring to the extracts of the affidavit and the impugned order. But Court said that whilst it is correct that the conclusions drawn by the Controller dealt with the issues referred in the impugned order, however, a careful reading of the affidavits and the conclusions drawn by the Controller clearly indicate that observations made in the impugned order are not directly relatable to the issues raised by Experts in his affidavit. The Controller has selectively culled out certain sentences from paragraphs 41, 42 and 44 of the affidavit filed by one of the Expert, Mr Jung to indicate that the said issues had been considered in the impugned order. However, a plain reading of Mr Jung’s affidavit indicates that the conclusions drawn are not directly in reference to the said affidavit. Court also denied respondent’s argument that said affidavits are not relevant to subject matter of claims since it is related to clinical trials & marketing approval.

Court thus set aside the order & remanded the matter to the Controller to decide afresh.

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Esomeprazole & Naproxen - USA

On May 15, 2019, Federal Circuit reversed district court’s decision & found two Vimovo® patents invalid for lack of written description support.

Nuvo/Horizon/Pozen (Plaintiffs) owns US 6,926,907 (expiring on 02/28/2023) and US 8,557,285 (expiring on 05/31/2022) patents.  The two patents bear the same title, “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” and have nearly identical specifications. Dr. Reddy’s Laboratories, Inc., Mylan Pharmaceuticals, and Lupin Pharmaceuticals (Defendants) filed ANDAs to USFDA to market generic version of Vimovo®. Plaintiff initiated suit & following a bench trial district court upheld the asserted claims of US’907 and US’285 as nonobvious under 35 U.S.C. § 103, enabled under 35 U.S.C. § 112, and adequately described under § 112. District court also granted summary judgement of non-infringement with respect to Dr. Reddy’s second ANDA. Defendants appealed the written description rulings. They did not appeal the obviousness holding, the enablement decision. Plaintiff cross appealed the district court’s grant of summary judgment of non-infringement.

Claim 1 of the ’907 patent reads:

1. A pharmaceutical composition in unit dosage form suitable for oral administration to a patient, comprising:

(a) an acid inhibitor present in an amount effective to raise the gastric pH of said patient to at least 3.5 upon the administration of one or more of said unit dosage forms;

(b) a non-steroidal anti-inflammatory drug (NSAID) in an amount effective to reduce or eliminate pain or inflammation in said patient upon administration of one or more of said unit dosage forms;

and wherein said unit dosage form provides for coordinated release such that:

i) said NSAID is surrounded by a coating that, upon ingestion of said unit dosage form by said patient, prevents the release of essentially any NSAID from said dosage form unless the pH of the surrounding medium is 3.5 or higher;

ii) at least a portion of said acid inhibitor is not surrounded by an enteric coating and, upon ingestion of said unit dosage form by said patient, is released regardless of whether the pH of the surrounding medium is below 3.5 or above 3.5.

Claim 1 of the ’285 patent reads:

1. A pharmaceutical composition in unit dosage form comprising therapeutically effective amounts of:

(a) esomeprazole, wherein at least a portion of said esomeprazole is not surrounded by an enteric coating; and

(b) naproxen surrounded by a coating that inhibits its release from said unit dosage form unless said dosage form is in a medium with a pH of 3.5 or higher;

wherein said unit dosage form provides for release of said esomeprazole such that upon introduction of said unit dosage form into a medium, at least a portion of said esomeprazole is released regardless of the pH of the medium.

With respect to written description district court rejected all three arguments put forth by Generics. First, the court rejected the “comprising” written description argument. The Generics argued that, because of the “comprising” language in the ’285 patent’s claims, they allow for the drug formulation to include some uncoated naproxen that is released immediately regardless of the pH, which is not supported by the specification and goes against the concept of coordinated release that is at the heart of the patent’s invention.

Second, the district court rejected the “inhibit” written description argument. The Generics contended that, although the patent discloses only delayed release formulations, the claims of the ’285 patent recite a broader undescribed invention, namely sustained release as op-posed to coordinated release of naproxen.

Third, the district court rejected the “efficacy” written description argument. The Generics argued that, if they lose on their obviousness contention, then the claims lack written description support for the claimed effectiveness of uncoated PPI because ordinarily skilled artisans would not have expected it to work and the specification provides no experimental data or analytical reasoning showing the inventor possessed an effective uncoated PPI.

Upon appeal Federal Circuit with respect to “efficacy” argument said that district court’s analysis does not support its conclusion. The district court, after finding that the specification lacks “information regarding the efficacy of uncoated PPIs,” said it was enough that the specification described the immediate release of uncoated PPI and the potential disadvantages of enteric-coated PPI formulations. But that disclosure it pointed to in no way provides support for the claimed efficacy of uncoated PPI. Generics argued that the record evidence demonstrates that a person of ordinary skill in the art would not have known or understood that uncoated PPI is effective. And there is nothing in the specification of the patents-in-suit showing “that the inventor actually invented the invention claimed.” [Centocor, 636 F.3d at 1348 (emphasis added); accord Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc)].

Federal Circuit further said that in light of the fact that the specification provides nothing more than the mere claim that uncoated PPI might work, even though persons of ordinary skill in the art would not have thought it would work, the specification is fatally flawed. It does not demonstrate that the inventor possessed more than a mere wish or hope that uncoated PPI would work, and thus it does not demonstrate that he actually invented what he claimed: an amount of uncoated PPI that is effective to raise the gastric pH to at least 3.5. That conclusion is confirmed by the inventor’s, Dr. Plachetka’s, own testimony at trial during which he admit-ted that he only had a “general concept of coordinated delivery with acid inhibition” using uncoated PPI at the time he filed his first patent application. In this case, the inventor chose to claim the therapeutic effectiveness of uncoated PPI, but he did not adequately describe the efficacy of uncoated PPI so as to demonstrate to ordinarily skilled artisans that he possessed and actually invented what he claimed. And the evidence demonstrates that a person of ordinary skill in the art reading the specification would not have otherwise recognized, based on the disclosure of a formulation containing uncoated PPI, that it would be efficacious because he or she would not have expected uncoated PPI to raise gastric pH. Under those facts, the patent claims are invalid for lack of adequate written description pursuant to § 112.

Federal Circuit thus declined to address the Generics’ alternative argument that the pa-tents are also invalid under § 112. Also Nuvo’s cross-appeal challenging the district court’s grant of summary judgment of noninfringement with respect to Dr. Reddy’s second ANDA product and the ’907 patent found moot.

Abiraterone - USA

On May 14, 2019, Federal Circuit affirmed PTAB & District Court’s decision that Zytiga® method of use patent is invalid as obvious.

This is a consolidated appeal (may be first of its kind, fast paced) from PTAB & District Court which J&J filed after claims were found obvious over prior arts. US 8,822,438 claims treatment of prostate cancer with Abiraterone & Prednisone. Most of the arguments of J&J were on claim construction of term "treatment" by PTAB. J&J said it was errenous.

The PTAB construed the term “treatment” as “including the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the minimization or delay of the spread of cancer.”

But CAFC found no error in claim construction based on internal records. It found that treatment covers both "anticancer effect" & "palliative effect".  The specification states that antibiotic agents are one example of anti-cancer agents. Therefore, the specification explains that prednisone may be used as both a steroid and an anti-cancer agent. Thus, Prednisone disclosure as palliative effect in prior arts is relevant for obviousness analysis. Court said that if J&J wants to limit it to "anticancer effect" only then they should have done it in claims and should have kept the specification according to it. Even arguing that Prednisone effect should be limited to "anticancer effect", CAFC said that Wockhardt petition has additional "Sartor" reference which discloses role of Prednisone in prostate cancer. Therefore, in either way it does not alter the ultimate obviousness conclusion.

For more details visit previous posts mentioned below.

District court’s decision reported here:

http://pharmaipcircle.blogspot.com/2018/10/abiraterone-usa.html

PTAB’s short summary is here:

http://pharmaipcircle.blogspot.com/2018/01/abiraterone-usa.html

Everolimus – USA

On May 13, 2019, Federal Circuit affirmed district court’s decision that method of treatment claims of Afinitor® patent are not invalid as obvious.

Novartis own US 8,410,131 (expiring on May 01, 2026 with PED), which claims methods of using the compound everolimus to treat advanced renal cell carcinoma (“RCC”). West-Ward filed ANDA seeking to manufacture and sell generic versions of Afinitor, and Novartis filed this patent infringement suit in response. After a bench trial, the district court ruled that West-Ward failed to prove by clear and convincing evidence that claims 1–3 of the ’131 patent are invalid as obvious. West-Ward appealed.

Claim 1 reads:

1. A method for inhibiting growth of solid excretory system tumors in a subject, said method consisting of administering to said subject a therapeutically effective amount of a compound of formula I (Everolimus).

West-Ward argued before the district court that claims 1–3 would have been obvious over a temsirolimus reference Hidalgo 20005 (discloses phase I development  of rapamycin and temsirolimus) or Hutchinson (discloses updated results of phase I studies) and an everolimus patent (U.S. Patent No. 5,665,772 or U.S. Patent No. 6,004,973), in view of the general knowledge in the art. According to West-Ward, knowledge in the art about the molecular biology of advanced RCC, the antitumor activity of mTOR inhibitors, phase I temsirolimus clinical trial results, and safe dosing ranges for everolimus, would have provided a person of ordinary skill with a reasonable expectation of success of effectively treating advanced RCC with everolimus. The district court found that a person of ordinary skill “would have been motivated to pursue everolimus as one of several potential treatment options for advanced solid tumors, including advanced RCC.” However, it ultimately determined that West-Ward “failed to prove by clear and convincing evidence that a POSA would have been motivated to select everolimus.” District court noted that there were a variety of other treatments in development at the time of the invention and that the knowledge gaps in the molecular biology of advanced RCC would have led a person of ordinary skill to search for art beyond those involving mTOR modulations.

In addition, the district court determined that the asserted prior art would not have provided a person of ordinary skill in the art with a reasonable expectation of success in using everolimus to treat advanced RCC. The district court explained that the temsirolimus phase I data disclosed in Hutchinson had diminished weight because it resulted from small sample sizes and because phase I clinical trials are designed to determine safety, not efficacy. It further noted that everolimus and temsirolimus differed in pharmacological properties relevant to treatment. These differences, along with the high failure rate of cancer drugs in phase II and III clinical trials, and the fact that the molecular pathways of advanced RCC were not fully understood, all diminished the relevance of the temsirolimus data. Based on these facts, the district court found that West-Ward failed to establish by clear and convincing evidence that a person of skill in the art would have reasonably expected everolimus to effectively treat advanced RCC.

Federal Circuit upon appeal said that district court erred in its analysis of “motivation to combine”. However, there was no clear error in the district court’s finding that a person of ordinary skill would not have “reasonably expected success” in using everolimus to treat advanced RCC as of February 2001.

With respect to motivation to combine, Federal Circuit said that after reviewing the prior art, the district court found that a person of ordinary skill “would have been motivated to pursue everolimus as one of several potential treatment options for advanced solid tumors, including advanced RCC.” Yet, the district court continued its analysis and found that West-Ward “failed to prove by clear and convincing evidence that a POSA would have been motivated to select everolimus.” The district court erred in applying this heightened standard. “[O]ur case law does not require that a particular combination must be the preferred, or the most desirable, combination described in the prior art in order to provide motivation for the current invention.”[In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004); see also Bayer Healthcare Pharm., Inc. v. Watson Pharm., Inc., 713 F.3d 1369, 1376 (Fed. Cir. 2013)]. Novartis argued that the district court did not err in concluding that the prior art fails to provide motivation to select everolimus. But Federal Circuit said that this is not a lead compound analysis. The ’131 patent claims methods of using everolimus to inhibit growth of solid tumors, including in patients having advanced RCC. The district court, however, appeared to apply or conflate the standard for these types of cases by requiring clear and convincing evidence that a person of ordinary skill “would have been motivated to select everolimus.” The proper inquiry should be whether a person of ordinary skill would have been motivated to modify the prior art disclosing use of temsirolimus to treat advanced RCC with the prior art disclosing everolimus.

With respect to Reasonable Expectation of Success, West-ward argued that the district court erred by imposing “a heightened standard under which it found no reasonable expectation of success simply because there was not yet clinical proof that everolimus would successfully treat advanced RCC.” Federal Circuit sided with district court & saw no clear error on this issue. Federal Circuit said that the district court correctly recognized that the temsirolimus phase I data resulted from small sample sizes and came from studies that were designed to test safety, not efficacy. Further, it considered the testimony of West-Ward’s expert Dr. Cho, who stated that a person of ordinary skill “would not make a determination or reasonable suggestion simply based in isolation upon whether a drug enters phase II,” and who did not dispute that more than seventy percent of oncology drugs failed at phase II. The district court also considered evidence that everolimus and temsirolimus are pharmacologically different. In addition, the district court considered several prior art references in finding that the roles of HIF-1 and mTOR in the molecular biology of advanced RCC were not fully understood as of February 2001.

Thus, federal Circuit affirmed district court & held that claims 1–3 of the ’131 patent would not have been obvious in view of the asserted prior art.

Bendamustine - USA

On May 09, 2019 Delaware Court granted Slayback’s motion for judgment on pleadings that its NDA does not infringe Eagle’s patents under Doctrine of Equivalents (DOE).

Eagle is the holder of NDA for BALRAPZO® (bendamustine) that was approved by FDA to treat patients with chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Eagle sued Slayback Pharma alleging infringement under the doctrine of equivalents of four patents: U.S. Patent Nos. 9,265,831, 9,572,796, 9,572,797 and 10,010,533 (all expiring on 01/28/2031). Eagle initiated this lawsuit in response to Slayback's submission of NDA No. 212209 for approval to manufacture and sell before the four asserted patents expire. All the independent claims of the patents require the presence of three limitations in the claimed pharmaceutical composition: (I) bendamustine or a pharmaceutically acceptable salt thereof; (2) a pharmaceutically acceptable fluid that contains some combination of two solvents: propylene glycol and polyethylene glycol; and (3) a stabilizing amount of an antioxidant.

Slay back's motion focuses on the second claim limitation-a pharmaceutically acceptable fluid that contains some combination of propylene glycol and polyethylene glycol. Slayback's proposed bendamustine drug contains polyethylene glycol, but instead of propylene glycol it uses another, second solvent. Eagle alleges that Slayback's drug infringes the solvent limitation under the doctrine of equivalents. Slayback had moved to dismiss on the ground that the so-called disclosure-dedication doctrine bars application of the doctrine of equivalents to the solvent limitation.

Court’s analysis:

The sole issue was whether, under the disclosure-dedication doctrine, the asserted patents' disclosure of Slayback' s second solvent as an alternative to propylene glycol bars Eagle from claiming that Slayback's drug infringes the solvent limitation under the doctrine of equivalents. Court said that under the disclosure-dedication doctrine, a patentee can disclaim an equivalent by disclosing the equivalent in the written description but not claiming it. [SanDisk Corp. v. Kingston Tech. Co., 695 F.3d 1348, 1363 (Fed. Cir. 2012)]. Furthermore, "before unclaimed subject matter is deemed to have been dedicated to the public, that unclaimed subject matter must have been identified by the patentee as an alternative to a claim limitation."[Pfizer, Inc. v. Teva Pharm. USA, Inc., 429 F.3d 1364, 1379 (Fed. Cir. 2005)].

Court said that the written description of the asserted patents explicitly and repeatedly identifies Slayback's second solvent as an alternative to propylene glycol in embodiments of the patented invention:

“In other aspects of the invention, the bendamustine containing compositions include a) a pharmaceutically acceptable fluid which contains one or more of propylene glycol, ethanol, polyethylene glycol, benzyl alcohol and glycofurol, and b) a stabilizing amount of a chloride salt”.

Despite these disclosures, Eagle made two arguments against applying the disclosure-dedication doctrine. First, it contends that the Federal Circuit's decision in “Nalco Co. v. Chem-Mod, LLC, 883 F. 3d 1337 (Fed. Cir. 2018)” prohibits application of the disclosure-dedication doctrine at the Rule 12(c) stage. Second, Eagle argues that it would be inappropriate to grant Slayback's motion at this time because Slayback has not shown that a person of ordinary skill in the art (POSITA) would understand the patents' written description to teach the use of Slayback's second solvent as an alternative to propylene glycol in the claimed formulation.

Court denied both the arguments. With respect to first argument court said that, Nalco does not prohibit the Court from applying the Disclosure-Dedication Doctrine at the Rule 12(c) stage because Nalco did not address the disclosure-dedication doctrine & Nalco did not hold that all "questions over the proper interpretation of a patent's intrinsic record are 'not suitable' and 'particularly inappropriate' for resolution on a motion to dismiss."  With respect to second argument court said that, Eagle's attempt to confine the disclosure-dedication doctrine to cases where an alleged infringer's exact formulation is disclosed in the written description, however, is contrary to established Federal Circuit precedent. Under Federal Circuit law, the disclosure-dedication doctrine applies to unclaimed subject matter that is "identified by the patentee as an alternative to a claim limitation." In this case, the solvent limitation is the claim limitation at issue, and the written description of the asserted patents repeatedly identifies Slayback's second solvent as an alternative to one of the two solvents recited in that limitation (i.e., propylene glycol).

Court thus finally held that it would be clear to a POSITA that the asserted patents disclose Slayback's second solvent as an alternative to propylene glycol, a claim limitation found in each of the independent claims. Therefore, Eagle is barred by the disclosure-dedication doctrine from alleging, based on Slayback's substitution of Slayback's second solvent for propylene glycol, that Slayback's proposed bendamustine drug product infringes the solvent claim limitation under the doctrine of equivalents.

Filgrastim & Pegfilgrastim – USA

On May 08, 2019, Federal Circuit affirmed district court’s decision that Sandoz’s biosimilar products do not infringe Amgen’s patents.

Amgen owns & markets filgrastim (Neupogen®) and pegfilgrastim (Neulasta®) products for treating neutropenia, a deficiency of white blood cells. Sandoz submitted BLA application to USFDA to market biosimilar version of Amgen’s product.  Amgen then  sued Sandoz for infringement. The court construed claims of U.S. Patents 6,162,427 and 8,940,878 and granted summary judgment of non-infringement of claim 7 of the ’878 patent to Sandoz. The ’878 patent discloses methods of protein purification by adsorbent chromatography. Claim 7 of US’878 patent relates to method of purifying a protein with sequential steps. The ’427 patent discloses methods of treating “diseases requiring peripheral stem cell transplantation.” Claim 1 of US’427 requires first administering G-CSF & thereafter disease treating effective amount of at least one chemotherapeutic agent.

The district court construed “disease treating-effective amount of at least one chemotherapeutic agent” in claim 1 of the ’427 patent as limited to “[a]n amount sufficient to treat a disease for which at least one chemotherapeutic agent is prescribed.” The court thereby rejected Amgen’s argument that the amount must be “sufficient to enhance the mobilization of stem cells.” Amgen thereafter stipulated to noninfringement of the ’427 patent contingent upon its right to appeal from the district court’s claim construction order. With respect to the ’878 patent, the district court construed limitations (f) and (g) of claim 7 (the “washing” and “eluting” steps) as separate steps and further clarified that the eluting step “must occur after the step of ‘washing the separation matrix.’ Since it is undisputed that Sandoz’s process only involves one step—applying the refold solution to the matrix, with no separate washing or eluting steps—the district court granted summary judgment that neither Zarxio® nor Sandoz’s proposed pegfilgrastim biosimilar infringes claim 7 of the ’878 patent.

US’878 patent

Claim 7 reads:

7. A method of purifying a protein expressed in a non-native limited solubility form in a non-mammalian expression system comprising:

(a) expressing a protein in a non-native limited solubility form in a non-mammalian cell;

(b) lysing a non-mammalian cell;

(c) solubilizing the expressed protein in a solubilization solution comprising one or more of the following: (i) a denaturant; (ii) a reductant; and (iii) a surfactant;

(d) forming a refold solution comprising the solubilization solution and a refold buffer, the refold buffer comprising one or more of the following: (i) a denaturant; (ii) an aggregation suppressor; (iii) a protein stabilizer; and (iv) a redox component;

(e) directly applying the refold solution to a separation matrix under conditions suitable for the protein to associate with the matrix;

(f) washing the separation matrix; and

(g) eluting the protein from the separation matrix, wherein the separation matrix is a non-affinity resin selected from the group consisting of ion exchange, mixed mode, and a hydrophobic interaction resin.

Upon appeal Federal Circuit reviewed district court’s claim construction de novo. Amgen contended that the district court misconstrued the “washing” and “eluting” claim limitations in both its claim construction and summary judgment decisions as requiring distinct solutions added to the matrix at different times. Instead, Amgen argued, the claims cover any number of solutions or steps as long as the functions of washing and eluting happen in sequence. Sandoz responds that the claim logically requires a series of steps & process claim is properly limited to a certain order of steps “‘when the claim language requires that the steps be performed in the order written, or the specification directly or implicitly requires’ an order of steps. Federal Circuit agreed with Sandoz & district court. It held that the washing and eluting steps of claim 7 require discrete solutions. Second, washing and eluting are consistently described in the specification as separate steps performed by different solutions.

Amgen next argued that the district court erred by rejecting its argument that Sandoz’s process infringes claim 7 through the doctrine of equivalents. Specifically, Amgen argued that Sandoz’s one-step, one-solution process is insubstantially different from the claimed three-step, three-solution process because it “achieves the same functions (washing and eluting), in substantially the same way (binding protein preferentially compared to contaminants, and then raising salt concentration to reverse protein binding) to achieve the same result (protein purification).” Sandoz responded that the district court properly analyzed Amgen’s argument and found that Sandoz’s one-step, one-solution process accomplishes purification in a different way from the claimed method and, as a result, is not equivalent. Federal Circuit again agreed with Sandoz and concluded that the district court correctly held that Sandoz’s one-step, one-solution process does not function in the same way as the claimed process. District court correctly held that, the claim recites a sequence of steps requiring application of “refolding,” “washing,” and “eluting” solutions, and our precedent prohibits us from overriding the natural language of claim 7 to extend these limitations to cover nearly any type of adsorbent chromatographic separation. The doctrine of equivalents applies only in exceptional cases and is not “simply the second prong of every infringement charge, regularly available to extend protection beyond the scope of the claims.” London v. Carson Pirie Scott & Co., 946 F.2d 1534, 1538 (Fed. Cir. 1991). Accordingly, the district court was correct to grant summary judgment that Sandoz does not infringe claim 7 under the doctrine of equivalents.

US’427 patent

Claim 1 reads:

1. A method of treating a disease requiring peripheral stem cell transplantation in a patient in need of such treatment, comprising

administering to the patient a hematopoietic stem cell mobilizing-effective amount of G-CSF;

and thereafter administering to the patient a disease treating-effective amount of at least one chemotherapeutic agent.

Amgen argued that the district court misconstrued the limitation of “disease treating-effective amount” of a chemotherapeutic agent in claim 1 of the ’427 patent as “an amount sufficient to treat a disease for which at least one chemotherapeutic agent is prescribed.” Specifically, Amgen asserted that the phrase only limits the amount of the chemotherapeutic agent administered and that the method of claim 1 encompasses “situations where the chemotherapeutic agent is prescribed only for stem cell mobilization rather than treatment of an underlying disease.” Sandoz responded that Amgen’s construction would read disease treatment out of the claim and collapse the claim’s textual distinction between a “stem cell mobilizing-effective amount” of G-CSF and a “disease treating-effective amount” of the chemotherapeutic agent. Federal Circuit agreed with Sandoz & held that “disease treating” requires that the chemotherapeutic agent be administered to treat an underlying disease. The claimed method therefore must be performed to treat an underlying disease. As the claim itself states, the “disease treating-effective amount” of a chemotherapeutic agent does precisely that. Court further said that Amgen’s construction would broaden claim 1 to cover administration of G-CSF and a chemotherapeutic agent solely for the purpose of mobilizing stem cells. Such a conclusion would require interpreting “disease treating” as “stem cell mobilizing,” but “[o]ur precedent instructs that different claim terms are presumed to have different meanings.” Finally, Federal Circuit held that the district court did not err in construing claim 1 of the ’427 patent & affirmed the Summary Judgment decision.

Bimatoprost - UK

On May 03, 2019, UK high court found low dose Lumigan® patent invalid under obviousness.

Allergan markets product containing 0.1 mg/ml (0.01%) bimatoprost for ophthalmic administration for the treatment of glaucoma under the trade mark Lumigan® 0.1 mg/ml. This replaced an earlier product called Lumigan® 0.3 mg/ml that contained 0.3 mg/ml (0.03%) bimatoprost.  Allergan is the proprietor of European Patent (UK) No. 1 753 434 entitled "Enhanced bimatoprost ophthalmic solution". In essence, the invention claimed in the Patent is a formulation containing a lower concentration of bimatoprost (in particular 0.01%, rather than 0.03%) and a higher concentration of a preservative called benzalkonium chloride ("BAK") (in particular, 200 ppm or 0.02% rather than 50 ppm or 0.005%). Aspire Pharma Ltd and Accord Healthcare Ltd (Defendants) obtained marketing authorisations for generic versions of Lumigan 0.1 mg/ml. Defendants do not dispute the infringement, however, they contend that the Patent is invalid on the ground that the claimed inventions were obvious over Laibovitz et al.

The main dispute was whether it was common general knowledge that BAK enhanced the corneal permeability, and hence bioavailability, of ophthalmic drugs. It is common ground that the inventive concept of claim 18 is a formulation of 0.01% bimatoprost with 0.02% BAK (i.e. 200 ppm) for treating glaucoma. It is also common ground that the key difference between claim 18 and Laibovitz is that, whereas Laibovitz discloses the use of 0.01% bimatoprost to treat glaucoma, it does not disclose the use of 0.02% BAK.

Court said that the Defendants' case is straightforward. It starts from the proposition that the skilled ophthalmologist would be interested in reducing the incidence of conjunctival hyperaemia observed with Lumigan 0.3 mg/ml. Allergan do not to dispute this proposition. The skilled ophthalmologist would see from Laibovitz that 0.01% bimatoprost was reported to lower IOP by 20.7%, which the skilled ophthalmologist would regard as sufficient to be clinically useful for the treatment of glaucoma and ocular hypertension. The skilled ophthalmologist would expect that a lower dose of bimatoprost than 0.03% would reduce the incidence of hyperaemia, but would note that the quality of the hyperaemia data reported in Laibovitz was poor. An obvious course would therefore be to repeat the study with a better methodology for recording and scoring hyperaemia and more patients in order to generate better hyperaemia data and to confirm the IOP lowering efficacy of the bimatoprost doses, and in particular the 0.01% dose.

The Defendants also contended that it would be obvious to use a preserved formulation, and in particular a formulation preserved with BAK. Allergan disputed this. Counsel for Allergan accepted that it would be obvious in the light of Laibovitz to produce a formulation of 0.01% bimatoprost with 50 ppm BAK for a commercial product, but submitted that it would not be obvious to use 50 ppm BAK for the purpose of repeating Laibovitz because of the possibility that BAK would affect the incidence of hyperaemia. Court said that this is a hopeless argument. The question is whether the inclusion of BAK would be an obvious choice from a technical point of view. Laibovitz makes it clear that the only reason why preserved formulations were not used in the original study is because they were not available – it was not a deliberate decision for any scientific reason. When repeating Laibovitz, it would obviously be convenient to be able to use multi-use containers, which would require the use of a preserved formulation. Since BAK was the most commonly used preservative, it would be the obvious choice. For the reasons discussed above, the skilled team would think that the hyperaemia associated with Lumigan 0.3 mg/ml was due to the bimatoprost, and not to the BAK. Accordingly, they would have no reason not to include BAK when repeating Laibovitz.

The Defendants also contended that the inclusion of anywhere from 50 ppm to 200 ppm BAK as a preservative would be obvious given the use of that range in the commercially available PGA eye drops. Allergan again disputed this. Allergan argued that, even if they included preservative at all, the skilled team would not include more than the minimum level of BAK i.e. 50 ppm. Court said that the inclusion of anywhere from 50 ppm to 200 ppm BAK was an entirely obvious choice. It was common general knowledge that BAK was generally used in the range from 40 ppm to 200 ppm. It was also common general knowledge that BAK was used in the range 50 ppm to 200 ppm in the commercially available PGA eye drops. Furthermore, the skilled team would have no reason to think that the inclusion of 200 ppm BAK in either 0.01% or 0.03% bimatoprost would have any adverse impact on the efficacy of the bimatoprost.

In the alternative, even if it was not obvious to include 200 ppm BAK purely as a preservative, the Defendants contended that it would have been obvious to try to optimise the bioavailability of bimatoprost by using BAK's additional property as a corneal permeation enhancer. This would be particularly useful for the lower doses of bimatoprost, given that Laibovitz indicates that they are not as efficacious as the 0.03% dose. The skilled team would expect that increasing the level of BAK from 50 ppm to 200 ppm would not only be safe and tolerable, but also would be likely to enhance the corneal permeation of bimatoprost, and hence its bioavailability and efficacy. Court agreed with Defendants & held that the inclusion of 200 ppm BAK in the lower doses of bimatoprost in order to increase the bioavailability of bimatoprost was obvious to try when repeating Laibovitz, and the skilled team would have a good expectation of success. Therefore, the Patent is invalid.

Cinacalcet - USA

On May 02, 2019 Delaware court denied Amgen’s request for preliminary injunction as it failed to show a likelihood of success on its claim that Cipla breached the agreement by selling the product.

Background:

Cipla "at-risk" launched their generic cinacalcet drug product, prior to the expiration of US 9,375,405 (the '"405 patent"), which is owned by Amgen. In earlier litigation, Amgen alleged that the Cipla product infringes Amgen's '405 patent. The parties settled the prior case by executing an agreement (the "Amgen-Cipla Agreement"), by which, among other things, Cipla agreed that: (i) the Cipla Product infringes the '405 patent, (ii) the claims of the '405 patent are valid and enforceable, (iii) Cipla will not (except under limited circumstances) begin to market the Cipla Product until 97 days before expiration of the '405 patent, and (iv) the Cipla Product will be licensed from on and after that agreed-upon launch date.

But other ANDA filers went to trial with respect to US’405 patent. The Honorable Mitchell S. Goldberg, issued a detailed opinion on Aug 24, 2018 finding that Teva & Piramal do not infringe & Zydus infringes the '405 patent. On Dec 28, 2018, Teva began to sell its product, although several days later Teva entered into a settlement agreement (Jan 02, 2019) with Amgen, by which it purportedly agreed to stop selling the Teva Product.  Under this Agreement, and despite having prevailed at trial and obtained a final judgment of non-infringement, Teva stipulated that the Teva product does infringe the '405 patent, which Teva further stipulated was valid and enforceable. Teva also agreed to pay Amgen up to $40 million dollars, depending (in part) on how long the cinacalcet market remains free of non-Amgen and non-Teva generic products, and appears to have agreed to stop selling the Teva Product.

Shortly after Teva's brief entry and exit from the market, Cipla on Jan 08, 2019 filed the instant suit, seeking a declaratory judgment that, under the terms of the Amgen-Cipla Agreement, and due to circumstances arising from the launch of the Teva Product, Cipla now had the right to launch the Cipla Product. When, soon thereafter, Cipla did begin to sell and offer for sale its Cipla Product, Amgen filed a motion for a preliminary injunction based on breach of contract.

Court’s analysis:

A preliminary injunction is "extraordinary" relief. It may be awarded only after the Court considers whether the moving party is likely to succeed on the merits of its claim, whether the moving party is likely to suffer irreparable harm in the absence of preliminary relief, the balance of equities between the parties, and the public interest.

Amgen seeks a preliminary injunction based on its claim that Cipla's launch of the product constitutes a breach of the Amgen-Cipla Agreement. Court said it will be necessary to discuss and dissect multiple provisions of the Amgen-Cipla Agreement. Specifically, Section 5.6 of the Amgen-Cipla Agreement reads as follows:

[1] Nothing in Section 5.5 or in this Settlement Agreement shall be construed to prevent Amgen from seeking any relief it is legally entitled to, including but not limited to damages and/or a permanent injunction, provided that Amgen can only seek such relief against the Defendants if Defendants launch Defendants' Product following a Third Party At Risk Launch, and if each Third Party with respect to its respective Third Party At Risk Launch (which At Risk Launch is either before or after an at risk launch by Defendants) is later found to infringe, or admits infringing, a valid and enforceable claim of the '405 patent and each such Third Party is required to pay, or agrees to pay, damages relating to its At Risk Launch.

[2] Notwithstanding anything to the contrary in this Settlement Agreement, if [i] any Third Party that has made an At Risk Launch of a Generic Cinacalcet Product (where such At Risk Launch is before or after an at risk launch by Defendants) is not found to have infringed one or more valid and enforceable claims of the '405 patent or [ii] has not ceased or agreed to cease selling such Generic Cinacalcet Product following an At Risk Launch, then Amgen shall not be entitled to seek or recover any relief from Defendants for Defendants' at risk sales, offers for sale, distribution, or importation of Defendants' Product.

Amgen, largely relying on the first sentence [1] of Section 5.6, contended that "[n]othing" in the Amgen-Cipla Agreement prevents it from seeking "any relief' against Cipla, including a preliminary injunction, except that Amgen can seek such relief against Cipla only if a third-party which launched its own product - here, the Teva Product - "is later found to infringe, or admits infringing, a valid and enforceable claim of the '405 patent and ... is required to pay, or agrees to pay, damages relating to its At Risk Launch."

Cipla, by contrast, relied almost entirely on the second sentence [2] of Section 5.6. Because sentence [2] begins "[n]otwithstanding anything to the contrary in this Settlement Agreement," Cipla insists that if its launch is authorized by this single sentence, then the Court need not be concerned with any other provision in the Amgen-Cipla Agreement, as this one sentence unambiguously authorizes the launch of the Cipla Product. Cipla further contends that this sentence [2] prohibits Amgen from seeking any relief- including a preliminary injunction, as well as damages following final judgment - for two independently sufficient reasons: (1) because Teva has been "not found to have infringed" the '405 patent; and (2) because Teva "has not ceased or agreed to cease selling" the Teva Product.

Court ultimately agreed with Cipla & said that Sentence [2] has essentially dispositive effect. Court said that Sentence [2] begins "[n]otwithstanding anything to the contrary in this Settlement Agreement." The clear and unambiguous meaning of this phrase is that regardless of whatever else one might find in any other provision or sentence of the Amgen-Cipla Agreement, the consequences of sentence [2] must be enforced. Moreover, there is no conflict between sentences [1] and [2]. Instead, the two sentences contain different restrictions on rights Amgen would otherwise have to seek relief from Cipla. It is necessary for Amgen to survive the restrictions of sentence [ 1] in order to obtain the relief it is seeking - but surviving those restrictions is not a sufficient  condition for obtaining such relief (where, as here, such relief is independently precluded by sentence [2]).

Court next said that Sentence [2] restricts Amgen if either condition [i] or [ii] is satisfied. The parties' next dispute involves how to read the conditions set out in sentence [2]. Amgen contended that the sentence [2] restriction on its entitlement to seek or recover relief relating to Cipla's At Risk Launch applies only if both of the conditions set out in sentence [2] are satisfied. Cipla, by contrast, asserted that Amgen is restricted by sentence [2] if even just one of the conditions of sentence [2] is met. Court held that this sentence clearly and unambiguously sets out two separate conditions, [i] and [ii], either of which, if satisfied, render applicable the restriction on Amgen contained in this provision. Sentence [2] uses the word "or" and so expresses two conditions, each of which is sufficient to bar Amgen from obtaining relief. Amgen's reading would, instead, effectively change the "or" to "and," requiring that the "then" consequence apply (and restrict Amgen) only if [i] and [ii] occur. But the Court is not permitted to rewrite the parties' clear and unambiguous contractual language.

Court further said that Condition [i] has been satisfied as Teva has been "not found to have infringed". In the earlier litigation, after trial and post-trial briefing, Judge Goldberg entered final judgment that "Watson [Teva] does not infringe any of the claims asserted against it." Section 5.6's reference to "not found to have infringed" does not require the finding of non-infringement to be a "Final Court Decision," as that term is defined in the Amgen-Cipla Agreement. The Amgen-Cipla Agreement requires exhaustion of appellate rights in order for there to be a Final Court Decision. But the term "Final Court Decision" does not appear in Section 5.6. Instead, the parties (presumably deliberately) here used the undefined term "not found to have infringed," which is exactly what occurred in the District Court patent litigation.

Court further said that Amgen is not entitled to "seek or recover any relief' for Cipla's At-Risk Launch. Amgen in another effort to evade the restriction of sentence [2] of Section 5.6 argued that this provision restricts Amgen only from seeking permanent injunctive relief and does not also bar Amgen from prevailing on its preliminary injunction motion. The Court disagreed & said that the plain language of sentence [2] precludes Amgen from seeking "any relief' if the conditions of the provision are satisfied. As the Court has already explained, condition [i] is satisfied. Preliminary injunctive relief is indisputably a type of relief and, therefore, is within the scope of "any relief." Therefore, Amgen is precluded from seeking (and precluded from recovering) preliminary and permanent relief in relation to Cipla's At Risk Launch of the Cipla Product.

Court further said that Condition [ii] will be treated as satisfied because of uncertainty as to whether Teva has "not ceased or agreed to cease selling" must be construed as Teva not ceasing or agreeing to cease selling. In pertinent part, Section 5.6 provides that if a third party that has made an at-risk launch "has not ceased or agreed to cease selling" its generic product, then Amgen is barred from seeking relief against Cipla for Cipla's At Risk Launch. Hence, for condition [ii] to be satisfied - making applicable the restriction on Amgen's ability to seek relief against Cipla - Teva must not have ceased nor have agreed to cease selling the Teva Product. While it may be that Teva has, in fact, ceased and/or agreed to have ceased selling its generic product, the record is not sufficiently clear, and at this stage doubts must be resolved against Amgen.  The record does establish, then, that Teva has ceased direct sales of the Teva Product, meaning that no additional dosages of the Teva Product have been injected into the market since January 2. However, that does not necessarily mean that indirect sales - in the form of those same dosages originally directly sold by Teva on or before January 2 moving through the drug "pipeline" (e.g., to wholesalers, pharmacies, and end users) - have also ceased. In fact, it is undisputed that ( at least as of the April 2 hearing) many bottles of Teva Product sold by Teva to wholesalers are still moving through the marketplace. Therefore, the Court will treat condition [ii] as being satisfied, presenting another basis for a finding of no likelihood of success on the merits.

Court next analyzed other factors such as Irreparable Harm, Balance of Equities & Public Interest , some of which were found in favor of Amgen. But finally court held that Amgen has not met its burden to show a likelihood of success on its claim that Cipla breached the Amgen-Cipla Agreement by selling Cipla Product. Thus, Court denied Amgen's motion for a preliminary injunction.

Job Update

................................................................................

Function: IPR-API

Position: Officer

Company: ZCL Chemicals Ltd.

Location: Ankaleshwar, Gujarat

Experience: 1-4 years

Qualification: MSc / BSc chemistry

Contact info: Srinivas.reddy@zclchemicals.com

................................................................................

If you know or have any vacancy in your IP department then you can contact me at: 
mahen_gunjal@yahoo.co.in 
WhatsApp: +91-7774007489

Oxymorphone - USA

On May 03, 2019, Federal Circuit affirmed district court’s decision that claims of pure Opana® patent are not obvious.

Actavis appealed the decision of Delaware court which found that Actavis failed to prove by clear & convincing evidence that claims of US 8,871,779 are obvious. Malilnckrodt/Endo owns US’779 patent which is related to compounds “morphinan alkaloid” such as oxymorphone & its process of preparation with low levels of α,β Unsaturated Ketones (low ABUK). Specifically patent relates to lowering of ABUK to level of 10ppm or 0.001%. Claim 1 of US’779 patent reads:

1.    A hydrochloride salt of oxymorphone comprising less than 0.001% of 14-hydroxymorphinone.

Actavis during appeal contended that district court erred by i) misconstruing the claim term “14-hydroxymorphinone” and ii) determining that asserted claims were not obvious in light of the prior arts.

Federal Circuit with respect to claim construction said that district court properly construed the term “14-hydroxymorphinone” mean to “14-hydroxymorphinone hydrochloride”.  Actavis argued that this term requires no construction because of the plain language of the claims & chemical differences between two compounds. But district court said that asserted claims requires “14-hydroxymorphinone” as part of salt or hydrochloride salt of the compound. Also intrinsic evidences along with extrinsic evidences support the district court’s construction.

Next, Federal Circuit with respect to obviousness said that district court did not clearly err in concluding that PHOSITA would lack reasonable expectation of success in combining prior arts, Weiss, Chapman & Rapoport. It said that although Weiss discloses method of purifying oxymorphone ABUK through catalytic hydrogenation, it does not provide key reaction conditions. Moreover, it also does not disclose degree of purification required by claims.  Chaperon in turn discloses process involving catalytic hydrogenation of oxycodone ABUK. Endo’s expert explained that this would likely be ineffective in achieving same purity with oxymorphoen as both are different moieties & requires different process conditions. PHOSITA would not have reasonable expectation of success in combining these two arts because there was material difficulty with using catalytic hydrogenation to purify oxymorphone to the FDA mandated level (FDA through communication asked to Malilnckrod/Endo to bring down impurity to 10 ppm level).

With respect to FDA communications in providing motivation to combine these prior arts, Federal Circuit sided with district court & held that the FDA communications recited a goal without teaching how the goal is attained. Therefore, these communications would not have been enough to overcome disclosures of Weiss, Chapman & Rapoport which indicate that PHOSITA would not reasonably believe their disclosed methods were fruitful to achieve FDA mandated oxymorphone purity level. This conclusion is further substantiated by the fact that inventors of US’779 patent engaged in extensive experimentation, involving much failure, to ultimately produce the oxymorphone of asserted claims. Thus, Federal Circuit affirmed that claims are not obvious.

Circuit Judge, STOLL dissenting:

Stoll said that district court erred by conflating the requirements of reasonable expectation of success and motivation to combine.  Specifically, district court required that the FDA communations to teach how to achieve the claimed invention in order to provide motivation to combine. But present case laws do not require this. If FDA communications also taught “how the goal is attained”, they would anticipate the asserted claims & then there is no need to address the obviousness. Moreover, patent specification is directed to specific process for achieving FDA’s objective. Patentee does not however, claims that process, instead it claimed FDA mandate itself. Therefore, Judge Stoll asked to remand to allow the district court to apply correct obviousness test & properly consider the role of FDA mandate which is the sole reason of US’779 patent’s existence.

Job Update

................................................................................
Function: IPR-Formulation

Position: Manager

Company: Glenmark

Location: Mahape, Navi Mumbai

Experience: 5-8 years

Qualification: M pharmacy/Pharmaceutics

Contact info:
 anubha.saboo@glenmarkpharma.com

................................................................................

Many thanks to my friend Mr Santosh Jagdale for sending this job update. If you know or have any vacancy in your IP department then you can contact me at: 
mahen_gunjal@yahoo.co.in 
WhatsApp: +91-7774007489

Zoledronic acid - USA

Decision on PGR: Apr 29, 2019

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	FINAL WRITTEN DECISION
PGR2018-00001	10/10/2017	05/01/2018	Grunenthal GmbH	9,539,268	Antecip Bioventures II LLC	Claims 3–30 are unpatentable

US 9,539,268 (Antecip Bioventures II LLC) – Non OB

1. A method of treating arthritis comprising orally administering a dosage form to a mammal in need thereof, wherein the dosage form comprises: ##STR00022## (Ion B) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or ##STR00023## (Ion C) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; wherein each A is independently an acidic functional group; wherein, if present, the bioavailability of Compound A in the dosage form is from about 1.1% to about 4%.

3. A method of treating arthritis comprising orally administering a dosage form to a human being suffering from arthritis, wherein the dosage form comprises: a) zoledronic acid in a salt or an acid form; or b) one of the following: 1) zoledronic acid in a salt or an acid form and ##STR00024## (Ion 1) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or 2) zoledronic acid in a salt or an acid form and ##STR00025## (Ion 2) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or 3) zoledronic acid in a salt or an acid form and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt or an acid form, Ion 1 in a salt form, or Ion 2 in a salt form; wherein any amount in % w/w is based upon the total weight of zoledronic acid in a salt or an acid form, Ion 1, Ion 2, and any corresponding counter ions; and wherein the bioavailability of zoledronic acid in the dosage form is about 1.1% to about 4%.

23. A pharmaceutical dosage form for oral administration comprising: a) zoledronic acid in a salt form; or b) one of the following: 1) zoledronic acid in a salt or an acid form and ##STR00026## (Ion 1) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; 2) zoledronic acid in a salt or an acid form and ##STR00027## (Ion 2) in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or 3) zoledronic acid in a salt or an acid form and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; wherein the dosage form is free of therapeutically active agents that are not zoledronic acid in a salt or an acid form, Ion 1 in a salt form, or Ion 2 in a salt form; wherein any amount in % w/w is based upon the total weight of zoledronic acid in a salt or an acid form, Ion 1, Ion 2, and any corresponding counter ions; and wherein the bioavailability of zoledronic acid in the dosage form is about 1.2% to about 4% in a human being.

PTAB decision:

Petitioner asserted various grounds such as 35 U.S.C. § 112(a) (lack of enablement), 35 U.S.C. § 112(b) (indefiniteness), 35 U.S.C. § 102 (anticipation) & 35 U.S.C. § 103 (obviousness) in its petition.

PTAB in summary with respect to “enablement” held that the specification includes no disclosure that explains how one may reliably distinguish dosage forms that fall within the scope of the claims from those that do not––short of preparing the forms and testing their bioavailability. The only example provided in the specification of the ’268 patent demonstrates the synthesis of compounds 1 and 2; it contains no guidance for selecting forms of zoledronic acid having the requisite bioavailability. The art of pharmaceutical dosage formulation is unpredictable.  Where an ordinarily skilled artisan would have understood that unmodified zoledronic acid has an oral bioavailability of less than 1%, that artisan could not have been expected to resolve, without any guidance, how to arrive at a dosage form having a bioavailability of 3% or 4%, without engaging in undue experimentation. Therefore, Petitioner has demonstrated by a preponderance of the evidence that claims 3–30 are unpatentable for lack of enablement under 35 U.S.C. § 112(a).

PTAB thus declined to reach other grounds of unpatentability asserted in the petition.