Ivermectin - USA

On Jan 29, 2020, Federal Circuit reversed & remanded district court’s decision of patent invalidity based on inherent anticipation.

Galderma is NDA holder for Soolantra®, a topical pharmaceutical formulation containing 1% ivermectin. It is indicated for the treatment of inflammatory lesions of rosacea, a skin disorder characterized by facial flushing and redness. Teva on Dec. 30, 2016 filed ANDA with FDA seeking to market generic version. Galderma sued Teva for infringement and asserted claim 12 of the 9,089,587 patent; claims 2, 3, and 6 of the 9,233,117 patent; and claims 6, 7, 10, and 11 of the 9,233,118 patent. The asserted claims recite methods of treating inflammatory lesions of rosacea through topical administration of 1% ivermectin once daily to patients with inflammatory lesions of rosacea. The claims also recite certain efficacy parameters resulting from the treatment methods.

Teva asserted that the claims at issue were invalid as anticipated by U.S. Patent No. 5,952,372 (“McDaniel”) or U.S. Patent No. 7,550,440 (“Manetta”). District court after trial issued opinion in favour of Teva & found asserted claims invalid under anticipation. The district court found that McDaniel expressly discloses: methods for treatment of rosacea, including inflammatory lesions; a topical formulation containing about 1–5% ivermectin; and, once-daily application of ivermectin. It also found that McDaniel inherently disclosed the claimed efficacy limitations. This finding of inherency was based on the parties’ stipulation that “Manetta enables McDaniel in 2012 as to the formulation.” According to district court POSA would have been able to practice McDaniel’s disclosed treatment method with Manetta’s formulation (Soolantra formulation) without undue experimentation.” Because court found all asserted claims invalid for anticipation, it did not reach Teva’s arguments concerning obviousness and lack of written description. 

         

On Sep. 6, 2019, Galderma timely filed a notice of appeal. On appeal, Galderma specifically challenged district court’s (1) use of multiple references for its anticipation analysis; and (2) finding of inherency based on “a mere possibility.”

1. Reliance on Multiple References -

Galderma argued that the district court erred by finding the asserted claims anticipated based on disclosures found in two references, in contravention of settled law that anticipation must be based on disclosure in a single reference. According to Galderma, although the district court was permitted to look to other references to interpret the allegedly anticipatory reference, it was strictly prohibited from using additional references “for a very specific teaching.” Particularly, Galderma argued that the district court erred by relying on second reference, Manetta for its teaching of the Soolantra formulation.  Galderma further argued that the district court confused enablement with anticipatory disclosure as Manetta’s enablement of McDaniel’s formulation only means that a POSA could practice the general formulations disclosed in McDaniel. It cannot mean that McDaniel discloses the specific formulation disclosed in Manetta.

Teva argued that the district court’s findings are consistent with precedent. It argued that disclosure of a genus (here, McDaniel’s disclosure of a 1–5% ivermectin formulation) can anticipate a claimed species if a POSA would discern or possess the species (here, the Soolantra formulation) upon reading the disclosure. According to Teva, Manetta’s Soolantra is “undoubtedly a species within the scope of McDaniel’s disclosure.”

Federal Circuit said that Teva’s arguments ignore the axiom that a patent claim can only be invalid for anticipation if a single reference discloses each and every limitation of the claimed invention. Turning to another reference “for a very specific teaching” runs afoul of these settled principles.  Dart Indus., 726 F.2d at 727 (rejecting an anticipation challenge where the challenger relied on two additional articles “for a very specific teaching, not for any light they shed on what [the anticipatory reference] would have meant to those skilled in the art”). Here, the district court erred by finding the asserted claims anticipated by the disclosures of McDaniel and Manetta, in contravention of settled law. Because teaching of Manetta is specific one & not a general to shed light on McDaniel disclosure. McDaniel does not contain the specific disclosure that is necessary for a finding of anticipation: an ivermectin formulation (such as Soolantra®) that necessarily achieves the claimed efficacy limitations.

2. Inherency Based on Mere Possibility –

On appeal, Galderma argued that the district court erroneously found that McDaniel inherently discloses the claimed efficacy limitations. According to Galderma, the district court erroneously based this conclusion on the mere possibility that a POSA would have been able to practice McDaniel’s disclosed method with Soolantra®. Federal Circuit sided with Galderma & said that the proper inquiry for inherent anticipation is whether the claimed efficacy limitations “necessarily result” from practicing McDaniel. District court erred here because McDaniel does not disclose the “very same composition” as the patents-in-suit; it only discloses topical ivermectin formulations generally. The record does not show that practicing McDaniel’s general disclosure of 1% ivermectin, “formulated into a cosmetically-acceptable topical lotion, cream, or gel,” necessarily achieves the claimed efficacy limitations. Moreover, Teva’s own formulation expert testified that formulation parameters such as excipients can impact drug release, which affects whether a formulation has “any sort of therapeutic value.”

Federal Circuit thus reversed and remanded for the district court to consider Teva’s remaining invalidity defenses.

Colchicine – USA

On Jan 27, 2020, Judge Richard G. Andrews of Delaware denied Takeda’s motion for a Preliminary Injunction to prohibit Defendant Mylan Pharmaceuticals Inc. from launching a generic version of the drug Colcrys®.

In 2016, Mylan filed ANDA with the FDA, seeking approval of a generic colchicine product & subsequently Takeda sued Mylan for infringement of its 17 patents. Parties then settled their lawsuit on November 7, 2017. As part of that settlement, the parties signed a License Agreement, which allows Mylan to sell a generic colchicine product, but only after a specified date.  Section 1.2 provides several situations, however, in which Mylan can launch its generic product before that date.

Section 1.2(d) states that Mylan is entitled to launch a generic at:

“The date that is [a specified time period] after the date of a Final Court Decision (as defined in Exhibit A) holding that all unexpired claims of the Licensed Patents that were asserted and adjudicated against a Third Party are either (i) not infringed, or (ii) any combination of not infringed and invalid or unenforceable”

Exhibit A defines a "Final Court Decision" as "the entry by a federal court of a final judgment from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken."

According to Mylan, Section 1.2(d) was triggered by this court’s decision in a separate case, Takeda Pharm. , US.A., Inc. v. West-Ward Pharm. Corp., No. 14-cv-1268-RGA (Mitigare product). In this litigation, Takeda asserted eight of its Colcrys patents against West-Ward, but, during summary judgment briefing, it dismissed five of them "with prejudice".  Court thus granted summary judgment of non-infringement on the remaining three patents.

On October 28, 2019, Mylan notified Takeda that it planned to "immediately start selling" a generic colchicine product "pursuant to the Parties' November 7, 2017 license agreement. Takeda sued Mylan on December 2, 2019 for patent infringement and breach of contract. Takeda then filed this motion for a Preliminary Injunction three days later, seeking to enjoin Mylan from launching the generic product.

Court’s analysis:

Court said that the critical issue here is whether Section 1.2(d) of the License Agreement permits Mylan to launch its generic colchicine product. Court said that it is undisputed that summary judgment decision in West-Ward was a "Final Court Decision."

Takeda argued that the West-Ward decision did not trigger Section 1.2(d) because court only ruled on the three patents that were still at issue, and not on the other five that Takeda had dismissed with prejudice. For Section 1.2(d) to apply, a court must find that "all unexpired claims of the Licensed Patents that were asserted and adjudicated against a Third Party are" not infringed or invalid. According to Takeda, only three patents were "adjudicated," while a total of eight were "asserted." Therefore, Takeda reasons, the summary judgment decision did not cover "all" unexpired claims of the Licensed Patents at issue.

Court however, disagreed & said that correct reading of the Section 1.2(d) applies to patent claims that were "asserted and adjudicated," not to patent claims that were "asserted or adjudicated." In West-Ward, claims from eight patents were "asserted," but claims from only three patents were "asserted and adjudicated." Thus, only those three patents matter for purposes of Section 1.2(d). Of the three patents that were "asserted and adjudicated" in West-Ward, "all" of their unexpired claims were found not infringed. That decision thus triggered Section 1.2(d), which "entitle[ s ]" Mylan to launch a generic version of Colcrys. Therefore Takeda has not shown it is likely to succeed on the merits of its patent infringement or breach of contract claims.

Takeda asserts that Mitigare, the drug in dispute in West-Ward, is not a generic version of Colcrys, and therefore the parties did not envision that a judgment involving Mitigare could trigger Section 1.2(d). Court said that Section 1.2(d) makes no mention of generic Colcrys products. By contrast, Sections 1.2(b) and 1.2(f) refer to the sale of a "Generic Equivalent" of Colcrys, and Section 1.2(e) refers to the sale of "Authorized Generic Products" of Colcrys. The parties therefore clearly knew how to condition provisions of the contract on the launch of generic Colcrys products, but they chose not to condition Section 1.2(d) in such a way. Moreover, West-Ward is a "Third Party" for purposes of Section 1.2(d). The Agreement defines a "Third Party" as a "Person other than a Party or an Affiliate of a Party," i.e., Takeda or Mylan. Section 1.2(d) is therefore not limited to situations where Takeda has sued claiming that a generic version of Colcrys infringes some or all of the Licensed Patents. The "Third Party" does not have to be another generic drug competitor. Rather, the provision can be triggered by a Takeda lawsuit against any entity other than Mylan or its affiliates.

Thus, Plaintiff's Motion for a Preliminary Injunction was DENIED. Court also did not grant any stay pending appeal, except that, in order to give Plaintiff an opportunity to seek immediate relief in the Court of Appeals, Defendant is ORDERED to maintain the status quo until end of the day January 31, 2020.

On same day (Jan 27, 2020) Takeda filed appeal in CAFC.

Dimethyl fumarate / Monomethyl fumarate – USA

On Jan 07, 2020, Chief Judge Leonard P. Stark of Delaware granted motion under Rule 12(c) for judgment on the pleadings for non-infringement to Baner Life Sciences.

Plaintiff Biogen International GmbH owns U.S. Patent No. 7,619,001 which is listed in OB for Tecfidera® (Dimethyl fumarate). US’001 patent originally set to expire on April 1, 2018 but Biogen filed PTE and thus term extended till June 20, 2020. On January 18, 2018, Banner submitted NDA under§ 505(b)(2), seeking approval for Bafiertam (monomethyl fumarate "MMF") delayed-release capsules for the treatment of Multiple Sclerosis. Banner received tentative approval from the FDA on November 16, 2018. Biogen sued Banner for infringement of the '001 Patent on December 27, 2018 within 45 days & obtained an automatic 30-month stay of FDA approval of Banner's Bafiertam product. Thus, at this time, the only impediment to Banner obtaining final FDA approval and having the right to market Bafiertam is the pendency of this litigation. Banner then moved under Rule 12(c) for judgment on the pleadings on the basis of non-infringement, reasoning that the '001 Patent's extension does not cover Banner's tentatively-approved product.

Relevant claims at issue here are claim 1 & claim 5:

1. A method of treating multiple sclerosis comprising administering ... an amount of a pharmaceutical preparation effective for treating multiple sclerosis, the pharmaceutical preparation comprising ... dimethyl fumarate [DMF], methyl hydrogen fumarate [MMF], or a combination thereof.

5. The method of claim 1, the pharmaceutical preparation comprising methyl hydrogen fumarate [MMF].

Court’s analysis:

Banner contended that the portion of the '001 patent that Bafiertam practices expired in April 2018. In Banner's view, Biogen's PTE applies only to the claimed embodiment which constitutes Biogen's FDA-approved DMF product, Tecfidera. The '001 patent was only extended, and can only be enforced, with respect to a DMF-containing product. Because Banner's Bafiertam contains MMF and not DMF, Banner argued it is entitled to judgment on the pleadings of no infringement.

The parties were in agreement that Biogen successfully obtained a PTE on its ' 001 patent until June 20, 2020 based on its FDA-approved product, Tecfidera. The parties disagree, however, on the scope of that extension and, particularly, whether it extends to Banner's MMF product. Court said that PTE extends the term of entire patent & not claim-by-claim basis. This does not mean, however, that Biogen, has the right to enforce the entirety of the ' 001 patent. Rather, § 156(b)2 limits the effect of the extension to the "rights derived'' under§ 156(a). Subsection 156(b)(2) limits the "rights derived" from a PTE "to any use [i] claimed by the patent and [ii] approved for the product." Under this reasoning, the '001 patent rights that Biogen may enforce during the extension period are limited to a method of treating MS using DMF (not MMF). On the contrary, Biogen reads§ 156(b)(2) as not just limited to the specific FDA-approved product/use combination (in this case, Tecfidera (DMF) for MS), but as also reaching any claim (or any portion of any claim) in the '001 patent directed to methods of treating MS. Thus, under Biogen's interpretation, the PTE applies to any drug product disclosed in the claimed methods of the '001 patent that can be used to treat MS, which in this case, would include the use of DMF, MMF, or any salts or esters thereof. Court, however, agreed with Banner's view as to the meaning of 156(b)(2).

Specifically, court said that pursuant to 35 U.S.C. 156(b), if the patent claims other products in addition to the approved product, the exclusive patent rights to the additional products expire with the original expiration date of the patent. In other words, the "rights derived" from the PTE do not extend to all embodiments within the scope of the claims that have been extended. Instead, those rights extend only to the claimed embodiment on which the extension is based, i.e., the FDA-approved drug product. Now therefore, the pertinent question here is: what is the "active ingredient" of Biogen's approved drug product, Tecfidera?  Is it dimethyl fumarate or monomethyl fumarate? (Dimethyl fumarate gets converted into monomethyl fumarate in the body which is an active form).

Banner argued that the "active ingredient" is the molecule found in the administered drug product before it is administered to the patient. Therefore, to Banner, the "active ingredient" of Tecfidera is DMF. Biogen, however, contends that Tecfidera's active ingredient is the active moiety, which here is MMF (as well as salts and esters of MMF). Both parties put forth reasonable interpretations of the statutory framework in light of two precedential Federal Circuit cases. Banner relies on Judge Michel's opinion in Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392 (Fed. Cir. 1990), which held that "active ingredient" refers to the molecule in the drug product to be administered, not the active moiety; while Biogen relies on Judge Newman's opinion in Pfizer v. Dr. Reddy 's Laboratories, 359 F.3d 1361 (Fed. Cir. 2004); which held that "active ingredient" for purposes of the PTE is active moiety in the body. However, in PhotoCure ASA v. Kappos, 603 F.3d at 1375, the Federal Circuit stated that its Glaxo and Pfizer decisions "are not in conflict." The Federal Circuit quoted Glaxo and reaffirmed that "a compound can only qualify as the 'active ingredient' of a drug if that compound itself is present in the drug." Further, PhotoCure emphatically states: "Pfizer did not change the law of§ 156." Rather, the Federal Circuit explained that "[t]he issue in Pfizer was whether infringement of an extended patent ... was avoided by changing the salt," and Pfizer's holding was that one cannot avoid infringement of an extended patent term simply by changing the salt of the active moiety.

Court said that given the Federal Circuit's instruction that there is no direct conflict between Glaxo and Pfizer, it must, consistent with Glaxo and the unambiguous meaning of§ 156(f)(2), look for the "active ingredient" of Biogen's FDA-approved product in that product at the time of administration, before the product is taken by a human patient. Here, the FDA-approved product that is the basis for the ' 001 patent's PTE is Biogen's Tecfidera. It is undisputed that the "active ingredient" in Tecfidera when administered (i.e., before it is ingested by a human patient) is DMF. Therefore, Biogen's enforceable, extended patent rights extend only to DMF. While DMF is an ester of MMF, MMF is neither a salt nor ester of DMF. Therefore, by operation of §156(b)(2) and 156(f)(2), Biogen has no enforceable rights during the patent extension period with respect to MMF. Thus, Court granted Banner's motion for judgment on the pleadings of non infringement.

Dexmedetomidine – USA

On Jan 09, 2020, Federal Circuit affirmed district court’s decision & found Precedex® premix patent invalid as inherently obvious.

Hospira is NDA holder for Precedex® (dexmedetomidine), used as a sedative in intensive medical care. Fresenius Kabi filed ANDA seeking approval for generic ready-to-use dexmedetomidine product. Hospira sued Fresenius for infringement of five patents and eventually dropped all but two claims, one of which was claim 6 of the US 8,648,106 patent which is dependant on claim 1.

Claim 1 is the only independent claim in the ’106 patent:

1. A ready to use liquid pharmaceutical composition for parenteral administration to a subject, comprising dexmedetomidine or a pharmaceutically acceptable salt thereof disposed within a sealed glass container, wherein the liquid pharmaceutical composition when stored in the glass container for at least five months exhibits no more than about 2% decrease in the concentration of dexmedetomidine.

6. The ready to use liquid pharmaceutical composition of claim 1, wherein the dexmedetomidine or pharmaceutically acceptable salt thereof is at a concentration of about 4 µg/mL.

Previously district court found that claim 6 of US’106 patent is invalid as obvious. Specifically, court held that prior arts disclosed exact embodiment of the current claimed formulation. Prior arts disclosed every limitation except “2% limitation”. Court said that this limitation is inherent when one practises the embodiment & thus claims are obvious. You can read the detailed discussion previously “reported here”.

Federal Ciruit decision:

Hospira appealed from the district court’s judgment mainly on 2 grounds. First, Hospira argued that the district court incorrectly considered the inherency of the about 2% limitation in non-prior art embodiments rather than the allegedly obvious prior art combination. Second, Hospira argued that the court applied a lower “reasonable expectation of success standard” rather than the higher “necessarily present” standard to the inherency question.

With respect to first point, Hospira argued that every tested sample of the 4 µg/mL preferred embodiment in the record was either from Hospira’s NDA for Precedex Premix or from Fresenius’s ANDA for its ready-to-use product, none of which were in the prior art. And those samples were manufactured using the particular manufacturing process described in Example 5 of the ’106 patent. Federal Circuit said that district court did not err in relying on data obtained after the priority date of the ’106 patent in its inherency analysis. Extrinsic evidence can be used to demonstrate what is “necessarily present” in a prior art embodiment even if the extrinsic evidence is not itself prior art. See Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co., 878 F.3d 1336, 1345 (Fed. Cir. 2018) (allowing “non-prior art data” to be used to support inherency). The later evidence is not itself prior art; it only helps to elucidate what the prior art consisted of. Therefore, it was not legally incorrect for the district court to rely on non-prior art data from Hospira’s NDA and Fresenius’s ANDA as evidence of the inherent stability of the 4 µg/mL preferred embodiment. Furthermore, the unclaimed manufacturing variables in Example 5 do not, as a matter of law, preclude a finding of inherency in this case. Claim 6 is directed to a composition of 4 µg/mL dexmedetomidine disposed in a sealed glass container.  Claim 6 is not a method claim, it is not a product-by-process claim, and there are no limitations in claim 6 regarding the manufacturing process by which the recited 4 µg/mL dexmedetomidine composition must be prepared. Importing such limitations from Example 5 into the claim, as Hospira seeks to do, would be improper.

Now since district court did not err, the question here is that whether the about 2% limitation was necessarily present in the 4 µg/mL preferred embodiment. At trial Fresenius evidence included data from more than 20 samples of the 4 µg/mL preferred embodiment, every one of which met the about 2% limitation. The evidence also included expert testimony that concentration does not affect the stability of dexmedetomidine, which demonstrates that dexmedetomidine is a very stable drug. Federal Circuit said that Hospira’s arguments on appeal cannot change the trial record, which included more than 20 samples that all met the about 2% limitation.

With respect to second point, Hospira argued that the district court applied the “reasonable expectation of success” standard in its inherency analysis rather than “necessarily present” standard. Federal Circuit sided with district court & said that its inherency analysis was correct. Court further said that the district court engaged in a thorough and extensive analysis of the stability data in the record to reach its factual finding that the about 2% limitation was necessarily present in the prior art. But the district court then engaged in unnecessary analysis in evaluating whether the chemical properties of the dexmedetomidine molecule, the information in the Precedex Concentrate and Dexdomitor labels, and the industry guidance for stability testing would enable a person of ordinary skill to have had a reasonable expectation of successfully achieving the about 2% limitation. The court thus conflated the standards for inherency and reasonable expectation of success. However, that was harmless error that did not infect its inherency analysis and findings. See Vanderbilt Univ. v. ICOS Corp., 601 F.3d 1297, 1308 (Fed. Cir. 2010). If a property of a composition is in fact inherent, there is no question of a reasonable expectation of success in achieving it. The claimed dexmedetomidine formulation already is, as the evidence in this case shows, possessed of the about 2% limitation. Thus district court’s factual findings were not clearly erroneous.

With respect to legal question of whether those findings support obviousness conclusion, Federal Circuit said that it is well-settled that the inclusion of an inherent, but undisclosed, property of a composition does not render a claim to the composition nonobvious. A patent can be invalid based on inherency when the patent itself makes clear that a limitation is “not an additional requirement imposed by the claims . . . , but rather a property necessarily present.” In re Kubin, 561 F.3d 1351, 1357 (Fed. Cir. 2009); see also Persion Pharm. LLC v. Alvogen Malta Operations Ltd., Case No. 18-2361, slip op. at 13 (Fed. Cir. Dec. 27, 2019). Here, the ’106 patent itself states that the invention was based on “the discovery that dexmedetomidine prepared in a premixed formulation . . . remains stable and active after prolonged storage.” Claim 6 does not recite any manufacturing limitations that are related to stability or an added component that enhances stability; it simply recites a composition, with a “wherein” clause that describes the stability of that recited composition, a result that was inherent in the prior art.

Cinacalcet - USA

On Jan 07, 2020, Federal Circuit affirmed district court’s decision as to Piramal, Zydus & vacated as to Amneal as district court erred in claim construction.

Amgen is NDA holder for Sensipar®(cinacalcet hydrochloride) used to treat secondary hyperparathyroidism in adult patients with chronic kidney disease who are on dialysis and to treat hypercalcemia in patients with parathyroid cancer and primary and secondary hyperparathyroidism. Amneal, Piramal, and Zydus each filed ANDA seeking to enter the market with a generic version of Sensipar®. Amgen brought suit against each ANDA filer alleging infringement of US 9,375,405 patent. Amgen asserted different claims against each defendant, but the parties stipulated that the infringement findings for claim 1 would extend to the majority of the remaining claims.

Claim 1 reads:

A pharmaceutical composition comprising:

(a) from about 10% to about 40% by weight of cinacalcet HCl in an amount of from about 20 mg to about 100 mg;

(b) from about 45% to about 85% by weight of a diluent selected from the group consisting of microcrystalline cellulose, starch, dicalcium phosphate, lactose, sorbitol, mannitol, sucrose, methyl dextrins, and mixtures thereof,

(c) from about 1% to about 5% by weight of at least one binder selected from the group consisting of povidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethylcellulose, and mixtures thereof; and

(d) from about 1% to 10% by weight of at least one disintegrant selected from the group consisting of crospovid[o]ne, sodium starch glycolate, croscarmellose sodium, and mixtures thereof,

wherein the percentage by weight is relative to the total weight of the composition, and wherein the composition is for the treatment of at least one of hyperparathyroidism, hyperphosphonia, hypercalcemia, and elevated calcium phosphorus product.

District Court decision:

In the district court litigation, the construction of the binder and disintegrant Markush groups was a key issue. Amgen argued that the Markush groups should be open to unrecited elements, but the district court disagreed. Relying on “Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350 (Fed. Cir. 2016)”, the court held that “Amgen ha[d] not overcome the very strong presumption that the Markush groups for the binder and disintegrant elements are closed to unrecited binders and disintegrants.” The district court held a bench trial on the issue of infringement. The court held that Amneal and Piramal do not infringe any claim of the ’405 patent but found that Zydus infringes. First, the district court found that Amneal does not infringe the asserted claims because its product does not meet the binder limitation. As a binder, Amneal uses Opadry Clear YS-1-7006, a product that contains hydroxypropyl methylcellulose (“HPMC”), polyethylene glycol 400, and polyethylene glycol 8000. Although HPMC is a listed binder, the court found that Opadry itself is not, so Amneal does not literally meet the binder limitation. Next, the district court found that Piramal does not infringe because it does not meet the binder limitation. Piramal uses pregelatinized starch which is not recited in claim. Amgen argued that the cold-water soluble fraction of the starch is equivalent to povidone, a listed binder. But the court rejected this argument as barred by prosecution history estoppel. During prosecution Amgen had narrowed its claims by accepting the Examiner’s Amendment to exclude binders different from those listed in the Markush group. In contrast, the district court found that Zydus’s ANDA product infringes the asserted claims. At issue for Zydus was the function of the pregelatinized starch in its formulation. Zydus’s ANDA states that the formulation uses pregelatinized starch as a diluent, and starch is listed in the diluent Markush group of claim 1. Zydus relied on testimony from Dr. Davies, Amgen’s expert,  that the cold-water soluble fraction of pregelatinized starch could function as an unlisted binder, but the court disagreed & found infringement.

Federal Ciruit decision:

Amgen appealed from the district court’s judgment that Amneal and Piramal do not infringe the ’405 patent. Zydus cross-appealed from the district court’s judgment that it infringed.

Amgen first challenged the district court’s construction of the binder and disintegrant Markush groups in, respectively, elements (c) and (d). The district court held both of these Markush groups to be closed. In reaching this result, the district court first compared claim 1 to that at issue in Multilayer, which similarly recited “comprising,” followed by “consisting of” terminology. The court explained that, as in Multilayer, there was a “very strong presumption” that the Markush groups were closed to unrecited constituents. Amgen argued that the “comprising” term renders the claim open-ended, even when other language restricts the scope of particular claim elements, and the “consisting of” term here only applies to the group from which “at least one” binder or disintegrant must be selected. Amgen also contrasts the binder and disintegrant limitations with the diluent limitation, which lacks the “at least one” language. Amgen maintains that the “at least one” language would be meaningless if the groups are closed to additional binders and disintegrants and meaningless in view of the claim’s recitations of “mixtures thereof” within the Markush groups. Amgen argues that its claims here are distinguishable from the Multilayer claims at issue in those cases because of the “at least one” limitation.

Federal Circuit said that defendants read more into Multilayer decision. Multilayer did not hold broadly that, whenever “consisting of” Markush group language is present in a particular claim limitation, even when the limitation follows a general claim transition phrase of “comprising,” all components of an accused product that perform the general function of the particular limitation must meet the requirements of that limitation, thus precluding components outside the Markush group. No such issue was presented in those cases. Rather, each decision held only that the terms of a particular claim limitation that used “consisting of” Markush group language were restricted to members of the Markush group. Those decisions do not apply in this case, where the question is whether the “binder” or “disintegrant” claim limitations are written to preclude other binders and disintegrants in the claimed composition.

The decisive issue in this case is critically different from any issue decided in Multilayer or Shire. The issue is whether all binders or disintegrants in the claimed formulation are subject to the specific binder or disintegrant limitations. Federal Circuit further said that there is no language in Amgen’s claim indicating that every binder or disintegrant in the claimed formulation must be within the Markush groups. Instead, the claim recites “at least one” binder or disintegrant “selected from the group consisting of” various excipients. And the limitations merely require that those particular binders or disintegrants meet the specified weight-percentage requirements, which is not inconsistent with the overall composition containing other binders or disintegrants. The plain language of this claim requires “at least one” of the Markush members and certainly does not indicate that the only binders and disintegrants in the claimed formulation are those listed in the groups.

Importantly, claim requires “comprising” language which means the claim does not preclude the presence of unrecited components or steps. Amgen’s use of the “comprising” transition phrase reinforces the conclusion that the language of those limitations is best construed not to foreclose such additional binders and disintegrants. Thus, optional additional binders and disintegrants not recited in the Markush group may be included in the claimed formulation. Without more, such language is satisfied when an accused product contains a component that is from the Markush group and that meets the limitation’s requirements for the component. It does not forbid infringement of the claim if an additional component is present functionally similar to the component identified in the Markush group limitation, unless there is a further basis in the claim language or other intrinsic evidence for precluding the presence of such additional components. Because the district court’s claim constructions in this case excluded formulations with additional unlisted ingredients—binders, disintegrants, or otherwise—those constructions are incorrect.

Now coming to Amneal’s product, Federal Circuit said that it uses “Opadry” as a binder. Opadry is a composite product comprised of HPMC, polyethylene glycol (“PEG”) 400, and PEG 8000. By containing Opadry, Amneal’s formulation necessarily contains HPMC. HPMC is a binder listed in the binder Markush group of claim 1, so, provided that Amneal’s formulation contains from about 1% to about 5% HPMC, irrespective of whether PEG is present, the formulation literally meets the binder limitation of claim 1.  There will of course be differences between HPMC alone as compared to Opadry, which is HPMC combined with PEG. But those differences cannot alter the conclusion that HPMC is present in Amneal’s formulation, even if it was added as a component of another commercially available product. The claim requires only that HPMC be present, not that HPMC’s physical characteristics or function be unaffected by additional ingredients. Federal Ciruit thus vacated & remanded asking district court to consider whether Amneal’s formulation contains “from about 1% to about 5% by weight” of HPMC, irrespective of the HPMC’s pairing with PEG.

With respect to Piramal’s product, Federal Circuit sided with district court & said that it correctly applied prosecution history estoppel. Piramal’s product uses pregelatinized starch as a binder, which is not listed in the binder Markush group of claim 1. Amgen during appeal argued that under the doctrine of equivalents that pregelatinized starch has a native starch fraction that functions as a diluent and a cold water soluble fraction that functions as a binder. But court court rejected Amgen’s doctrine of equivalents argument as barred by prosecution history estoppel. During prosecution, the examiner rejected Amgen’s claims for obviousness, and, in response, Amgen narrowed the the claim in an attempt to overcome the rejection. Piramal argued that Amgen’s acceptance of the Examiner’s Amendment led directly to the allowance of the claims. Piramal also argued that the addition of the Markush groups overcame the obviousness rejection. Court agreed with Piramal & held that Amgen’s doctrine of equivalents argument is barred by prosecution history estoppel.

With respect to Zydus’ product, Federal Circuit sided with district court & said that Zydus’s ANDA states that the pregelatinized starch in Zydus’s formulation functions as a diluent which is one of the claimed diluent.  Zydus argued that the starch also functions as a binder. To support its position, Zydus adopted the testimony of Dr. Davies, Amgen’s expert, that Amgen had proffered for its argument about Piramal’s formulation. Dr. Davies opined that pregelatinized starch’s native starch fraction functions as a diluent but that its cold water soluble fraction functions as a binder. But district court did not find Dr. Davies’s testimony credible for several reasons & found that Zydus’s ANDA product infringed claim 1. Federal Circuit thus agreed with district court & Amgen that the district court did not clearly err in finding that the pregelatinized starch in Zydus’s product functions as a diluent.