Brimonidine & Timolol – USA

On Aug 29, 2019, Federal Circuit affirmed district court’s decision of patent validity & preliminary injunction in Combigan® case.

This appeal concerns Allergan’s patents, U.S. Patent Nos. 9,770,453, 9,907,801, and 9,907,802. The These patents share common specification & are related to combination of Brimonidine and Timolol for topical ophthalmic use. Sandoz filed ANDA with USFDA to market generic version of Combigan®. Allergan sued Sandoz under Hatch-Waxman regulation for infringement. New Jersey District Court found limiting a number of “wherein” clauses in these patents and granted Allergan’s motion for a preliminary injunction. Sandoz appealed.

Sole issue on appeal was with respect to the claim construction of clause, “wherein”. Sandoz argued that the wherein clause should be construed broadly because it is not limiting as it “merely state the intended results”. On the other side Allergan argued that the clause should be construed as limiting because “it is material to the patentability”.

Independent claim 1 of the ’453 patent is representative and recites:

 A  method of treating a patient with glaucoma or ocular hypertension comprising topically administering twice daily to an affected eye a single composition comprising 0.2% w/v brimonidine tartrate and 0.68% w/v timolol maleate, wherein the method is as effective as the administration of 0.2% w/v brimonidine tartrate monotherapy three times per day and wherein the method reduces the incidence of one o[r] more adverse events selected from the group consisting of conjunctival hyperemia, oral dryness, eye pruritus, allergic conjunctivitis, foreign body sensation, conjunctival folliculosis, and somnolence when compared to the administration of 0.2% w/v brimonidine tartrate monotherapy three times daily.

Federal Circuit said that wherein clause of claim 1 recites both efficacy & safety. It further said that though there is overlap between the language of the “wherein” clauses and those results, claims should be read in view of the “entire specification.”  The specification of the Patents-in-Suit demonstrates that the claimed invention is ultimately a formulation (and methods of using that formulation) that allows for increased efficacy and safety, i.e., a decreased risk of adverse events. Example II clinical study of the specification directly compares use of the Example I formulation with those prior art treatments and concludes that the claimed method is “superior” in both efficacy and safety. Thus, the specification demonstrates that Allergan believed the increased efficacy and safety of the claimed methods to be material to patentability. Allergan also relied on the efficacy and safety of the claimed methods during prosecution of the Patents-in-Suit in responding to the examiner’s rejections. Moreover, the Examiner explicitly relied on the “wherein” clauses in explaining why the claims of the Patents-in-Suit were “novel and non-obvious over the prior art.”

Therefore, in view of these strong intrinsic evidence, Federal Circuit sided with Allergan & held that the “wherein” clauses are material to patentability and thus limiting. Federal Circuit, thus found Sandoz’ arguments unpersuasive & held patents valid & affirmed injunction.

Dapsone - USA

IPR decision: Aug. 27, 2019

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	Final Decision
IPR2018-00608	02/12/2018	08/29/2018	Amneal Pharma. LLC	9,161,926	Allergan, Inc.	Claims 1–6 are patentable

US 9,161,926 (Allergan, Inc.; Exp: 11/18/2033) – listed in OB

1. A topical pharmaceutical composition comprising: about 7.5% w/w dapsone; about 30% w/w to about 40% w/w diethylene glycol monoethyl ether; about 2% w/w to about 6% w/w of a polymeric viscosity builder consisting of acrylamide/sodium acryloyldimethyl taurate copolymer; and water; wherein the composition does not comprise adapalene.

5. A topical pharmaceutical composition comprising: about 7.5% w/w dapsone; about 30% w/w diethylene glycol monoethyl ether; about 4% w/w of a polymeric viscosity builder consisting of acrylamide/sodium acryloyldimethyl taurate copolymer; and water; wherein the composition does not comprise adapalene.

Nitric oxide – USA

On Aug 27, 2019, Federal Circuit affirmed district court’s decision which found some patents ineligible & some non-infringed in INOmax® case.

This appeal concerns to INO Therapeutics & Mallinckrodt’s (Plaintiff), U.S. Patent Nos. 8,282,966, 8,293,284, 8,795,741, 8,431,163, and 8,846,112 (“heart failure patents” or “HF patents”) & U.S. Patent Nos. 8,573,209, 8,776,794, 8,776,795, 9,265,911 and 9,295,802 (“delivery system infrared patents” or “DSIR patents”). These patents are listed in Orange Book for INOmax®. Praxair (Defendant) filed ANDA with USFDA seeking approval to market Noxivent, a generic form of 100 and 800 ppm nitric oxide gas for inhalation. Plaintiff sued defendant in Delaware court. District of Delaware after bench trial held all claims of the HF patents ineligible under 35 USC 101 and all claims of the DSIR patents not infringed.

Ineligibility under 35 USC 101:

Claim 1 of the ’741 patent is representative. Claim 1 recites:

1. A method of treating patients who are candidates for inhaled nitric oxide treatment, which method reduces the risk that inhalation of nitric oxide gas will induce an increase in pulmonary capillary wedge pressure (PCWP) leading to pulmonary edema in neonatal patients with hypoxic respiratory failure, the method comprising:

(a) identifying a plurality of term or near-term neonatal patients who have hypoxic respiratory failure and are candidates for 20 ppm inhaled nitric oxide treatment;

(b) determining that a first patient of the plurality does not have left ventricular dysfunction;

(c) determining that a second patient of the plurality has left ventricular dysfunction, so is at particular risk of increased PCWP leading to pulmonary edema upon treatment with inhaled nitric oxide;

(d) administering 20 ppm inhaled nitric oxide treatment to the first patient; and

(e) excluding the second patient from treatment with inhaled nitric oxide, based on the determination that the second patient has left ventricular dysfunction, so is at particular risk of increased PCWP leading to pulmonary edema upon treatment with inhaled nitric oxide.

On appeal, Mallinckrodt argued that, the “exclusion” step is the reason the claims are not directed to a natural phenomenon as no treatment protocol had screened for reducing such an adverse event before. Federal Circuit, however, disagreed & said that claim 1 is “directed to” that observation about the natural phenomenon. As drafted, the claim instructs a physician to administer iNO gas to non-LVD patients as before, while now excluding the LVD patients. The exclusion step merely restates the natural law. Properly understood, this added step is simply an instruction not to act. Also, Mallinckrodt cannot dispute that the patented method does not propose a new way of treating LVD patients that leverages this discovery (e.g., by titrating the iNO dose). Instead, the claim simply requires that the patient not be treated with iNO.

Mallinckrodt further argued that claims cannot be directed to a natural phenomenon because they recite a treatment step. Specifically, claim 1 requires the affirmative act of “administering 20 ppm inhaled nitric oxide treatment”—a well-known dosage—to a patient without LVD. Federal Circuit again disagreed & said that a closer look at the claim language as a whole confirms that the focus of the invention is not on a new way of actually treating the underlying condition of hypoxic respiratory failure. Nor does it recite a way of reducing the risk of pulmonary edema while providing some level of treatment to those patients. Rather, the focus of the invention is screening for a particular adverse condition that, once identified, requires iNO treatment be withheld. Also, Mallinckrodt does not point to “any innovation other than its [purported] discovery of the natural law.”

Therefore, the claims here are readily distinguishable from other cases that actually integrate or leverage natural laws to an eligible method of treatment for a particular disease. The patent does not delve into the complexities of dosing to more effectively “treat” different classes of patients as in Vanda, Natural Alternatives, and Endo Pharmaceuticals—by leveraging knowledge about a natural correlation to understand what amounts of a particular drug prove therapeutic for each patient. Therefore, HF patents claims are ineligible under 35 USC 101.

Non-infringement of DSIR patents:

Claim 1 of the ’794 patent is representative of the device claims and reads:

1. A gas delivery device comprising:

a gas source to provide therapy gas comprising nitric oxide;

a valve attachable to the gas source, the valve including an inlet and an outlet in fluid communication and a valve actuator to open or close the valve to allow the gas through the valve to a control module that delivers the therapy gas comprising nitric oxide in an amount effective to treat or prevent hypoxic respiratory failure; and

a circuit including:

a memory to store gas data comprising one or more of gas identification, gas expiration date and gas concentration; and

a processor and a transceiver in communication with the memory to send and receive signals to communicate the gas data to the control module that controls gas delivery to a subject and to verify one or more of the gas identification, the gas concentration and that the gas is not expired.

On appeal with respect to DSIR patents, Mallinckrodt challenged issue with the district court’s interpretation of the “verify” term. Claim 1 of the ’794 patent requires the device “verify one or more of the gas identification, the gas concentration and that the gas is not expired.” The district court interpreted the claim term to require that the gas delivery system verify data about the actual gas in the “gas source” (i.e., the cylinder being used). Federal Circuit sided with district court & said that because Praxair’s delivery system (NOxBOXi) does not “verify” the gas either, it does not infringe the asserted claims. Mallinckrodt’s expert, Dr. Schaafsma, testified that the NOxBOXi’s gas data does not come from the gas source. Therefore, Praxair ANDA does not infringe the DSIR patents.

Ivermectin – USA

On Aug 21, 2019, Delaware court found Galderma’s method of treating rosacea patent invalid for anticipation.

Galderma sued Teva under Hatch-Waxman act for infringement of several patents listed in orange book for Soolantra® cream. Court held bench trial from June 10 to 12, 2019, focusing essentially on 3 patents; US 9,089,587, US 9,233,117, and US 9,233,118. Teva argued that asserted claims of these patents are invalid for lack of written description, anticipation, and obviousness. Broadly these patents are directed to methods of treating papulopustular rosacea. All of the asserted claims require (1) topically administering, (2) once daily, (3) to a skin area affected by the inflammatory lesions of rosacea, ( 4) a pharmaceutical composition comprising 1 % by weight ivermectin and a pharmaceutically acceptable carrier.

Anticipation:

Teva argues that the asserted claims are invalid as anticipated by either the McDaniel patent or the Manetta patent. McDaniel claims an invention relating to "a method for treatment of rosacea (acne rosacea) in humans employing orally-administered or topically-applied ivermectin." explicitly discloses an embodiment using topical ivermectin:

“Ivermectin is formulated into a cosmetically-acceptable topical lotion, cream, or gel and applied to skin affected by rosacea. Because of the well-known barrier effect the skin presents to the penetration of topical medications, such a route of treatment with ivermectin would be anticipated to require once or twice-daily applications for as long as four weeks to achieve sufficient follicle penetration and effective miticidal activity. A topical formulation that could achieve this effect would contain about 1-5% ivermectin”.

Thus, court said that McDaniel discloses every element of the claimed treatment method, ie. "topically administering",  "once daily", "to a skin area affected by the inflammatory lesions of papulopustular rosacea"  and  "a pharmaceutical composition comprising about 1 % by weight ivermectin and a pharmaceutically acceptable carrier".

Galderma argued that McDaniel fails to disclose (1) the use of topical ivermectin for the purpose of treating inflammatory lesions of papulopustular rosacea and (2) the use of 1 % ivermectin once daily.

With respect to first point, Galderma argued that McDaniel fails to disclose the use of ivermectin to treat inflammatory lesions because it discloses a method that "elicit lesion formation" and co-administers ivermectin with "conventional anti-rosacea medications." But court disagreed & said that any increase in lesion formation is temporary. Regardless, lesion formation is a measure of efficacy and is irrelevant to whether McDaniel discloses the steps of the treatment method. With respect to second point, Galderma argued that McDaniel's disclosure of "about 1-5% ivermectin" is not "sufficiently specific" to anticipate the asserted claims and is not connected to the once-daily dosing frequency. Court again disagreed & said that, although McDaniel discloses a genus of 1-5% ivermectin, there is no evidence that 1-5% is a particularly broad range for the purposes of the claimed treatment method. Galderma has made no allegation of criticality or provided any evidence demonstrating any difference across the range. There is thus no "considerable difference" between the 1 % ivermectin limitation and the 1-5% ivermectin range in McDaniel. Also, McDaniel ties the use of 1 % ivermectin to a once-daily dosage. McDaniel provides a clear reason to connect the disclosure of 1 % ivermectin with once-daily applications as it explicitly teaches the use of both elements together.

Court further said that, aside from the treatment method, the only remaining limitations are those relating to efficacy. "Under the principles of inherency, if the prior art necessarily functions in accordance with, or includes, the claimed limitations, it anticipates." [MEHL/Biophile Int'! Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999)]. Galderma argued that McDaniel's treatment of rosacea generally is insufficient for anticipation because it will not necessarily result in treatment of inflammatory lesions of papulopustular rosacea. But court said that, the issue is not whether McDaniel's formulation if applied would inherently treat inflammatory lesions of papulopustular rosacea, but whether McDaniel discloses the application of the formulation to inflammatory lesions of papulopustular rosacea. And court found that it does.

Court further said that, the only remaining issue is whether McDaniel also discloses using the same ivermectin formulation as in the asserted claims. The parties have stipulated, "Manetta enables McDaniel in 2012 as to the formulation." Thus, as of 2012, before the critical dates of the asserted claims, a person of ordinary skill in the art would have been able to practice McDaniel's disclosed treatment method with Manetta's formulation without undue experimentation. The Manetta formulation is the formulation for Galderma's product, Soolantra. Galderma argued that Teva has failed to meet its burden on anticipation because it must show that all 1 % ivermectin formulations disclosed in McDaniel would necessarily achieve the claimed efficacies. But court said that, it is well established that "[f]or a prior-art reference to be enabling, it need not enable the claim in its entirety, but instead the reference need only enable a single embodiment of the claim."

Court held that the asserted claims consist of the same steps described in McDaniel and are directed to the same use-treating inflammatory lesions of papulopustular rosacea. "Using the same composition claimed by [Galderma] in the same manner claimed by [Galderma] naturally results in the same claimed skin benefits." Therefore, the claimed efficacies are nothing more than "the natural result flowing from the explicit disclosure" of the claimed treatment method. As such, those efficacies are inherent to and anticipated by McDaniel's disclosure of the claimed treatment method.

Court thus did not address other invalidity arguments as each of the asserted claims found invalid for anticipation.

Plerixafor - USA

On Aug 16, 2019, Federal Circuit affirmed (Rule 36 judgment) district court that found Mozobil® patent valid & infringed.

District court decision:

Plaintiffs (Genzyme/Sanofi) alleged infringement of U.S. Patent No. 6,987,102 and U.S. Patent No. 7,897,590 both entitled "Methods to Mobilize Progenitor/Stem Cells," against Zydus, which filed ANDA with USFDA. Zydus stipulates to infringement, but responds in counterclaims that the asserted claims of the patents-in-suit are invalid. A four-day bench trial was held on March 26-27, 2018, and April 10-11, 2018. District court on Aug 8, 2018 rendered judgment & held that both patents are valid as Zydus failed to prove by clear & convincing evidence that asserted claims are obvious over cited prior arts. Specifically, court said that though there was motivation to combine the prior arts but there was no reasonable expectation of success. Because: 
1. Mechanism of action of stem cell mobilisation was unclear. 
2. Known agent such as G-CSF was known to increase the CXCR4 activity rather than decrease & 
3. Though some CXCR4 antagonist or antibodies have blocking activity but they were failed to mobilise sufficient quantity of stem cells. 
Moreover, some secondary considerations supported non-obviousness.

Naltrexone HCl & Bupropion HCl – USA

On Aug 15, 2019, Federal Circuit affirmed-in-part & reversed-in-part district court’s decision regarding Contrav® patents related to extended release composition & method of use patents.

This appeal is related to Nalpropion’s patents, US 7,375,111; US 7,462,626 and US 8,916,195. The ’626 patent is drawn to a method for treating over-weight or obesity comprising administering this combination. The ’195 patent is also directed to methods of treating overweight or obesity, but the claims are drawn to specific dosages of sustained-release naltrexone and bupropion that achieve a specific dissolution profile. The ’111 patent is directed to a composition of sustained-release bupropion and naltrexone for affecting weight loss.

Appellee Nalpropion Pharmaceuticals, Inc. holds NDA for & market Contrave® for weight management in overweight or obese adults. Actavis filed ANDA with USFDA to market generic version of Contrave®. In response to the infringement suit in district court, Actavis brought invalidity counter-claims, challenging claim 11 of the ’195 patent as invalid for lack of adequate written description and challenging claim 1 of the ’111 patent and claims 26 and 31 of the ’626 patents as invalid as obvious. The district court held a bench trial on all of these issues and held each claim not invalid and infringed. Actavis appealed.

a. Appeal regarding written description -

Claim 11 of the ’195 patent recites a method of treating overweight or obesity comprising orally administering about 16 mg of naltrexone and about 180 mg of bupropion, both in sustained-release formulations administered twice daily. This method claim also requires that the claimed naltrexone formulation have an in vitro dissolution profile. Actavis argued that claim 11 of the ’195 patent lacked adequate written description support because its claimed dissolution profile was achieved using the USP Apparatus 2 Paddle Method (“USP 2”), but the specification discloses data obtained using the different USP Apparatus 1 Basket Method (“USP 1”). According to Actavis, both inventor and expert testimony demonstrated that the two dissolution methods would produce different results.

Federal Circuit said that it is important to take note of the peculiarity of claim 11, which begins clearly enough by reciting a method of treating overweight or obesity by carrying out the specific, positive steps of administering a formulation of specific amounts of sustained-release naltrexone and bupropion in twice a day. Dissolution profile as measured by USP 2 relates only to the measurement of resultant in vitro parameters, not to the operative steps to treat over-weight or obesity. Federal Circuit sided with district court & said that, irrespective of the method of measurement used, the specification shows that the inventors possessed the invention of treating overweight or obesity with naltrexone and bupropion in particular amounts and adequately described it. District court correctly concluded, on the facts, that USP 1 and USP 2 would be “substantially equivalent.” Having found USP 1 and USP 2 substantially equiva-lent, the district court found Table 5 and Table 10 ade-quately supported the dissolution data ranges in claim 11.

Federal Circuit, however, said that…”While as a general matter written description may not be satisfied by so-called equivalent disclosure, in this case, buttressed by the district court’s fact-finding, and where the so-called equivalence relates only to resultant dissolution parameters rather than operative claim steps, we affirm the district court’s conclusion. Rigidity should yield to flexible, sensible interpretation”.

b. Appeal regarding obviousness –

Actavis challenged claim 1 of the ’111 patent and claims 26 and 31 of the ’626 patent as obvious in view of O’Malley and Jain. O’Malley (US 6,541,478) in general relates to Smoking Cessation Treatments Using Naltrexone and Related compounds. Claim 1 of O’Malley is drawn to a method of treating a person for nicotine dependency and minimizing weight gain during smoking cessation therapy comprising “administering . . . an effective amount of naltrexone and another compound selected from the group consisting of . . . bupropion. . . .” Jain is a research paper entitled “Bupropion SR vs. Placebo for Weight Loss in Obese Patients with Depressive Symptoms.” Jain discloses that “preliminary studies suggest that bupropion SR is also an effective adjunct to diet for weight loss during acute and long-term therapy in nondepressed patients” and “is associated with weight loss in overweight or obese depressed patients.

District court rejected Actavis’s obviousness argument & said that the weight loss effects of bupropion were known to be relatively modest at best, and prior art references reported potential risks, including a potential for seizures. Because a person of skill would not understand bupropion’s mechanism of action and because of its modest effectiveness, a person of skill would not have found bupropion to be an obvious starting point for further study. The district court was also convinced that a person of skill would not have understood naltrexone to be effective for weight loss. As for the combination of the two drugs, the district court concluded that prior arts did not teach a person of ordinary skill that the combination was effective for weight loss. According to the court, neither reference teaches anything about weight loss or that naltrexone enhances bupropion’s weight loss effects.

On appeal, the parties primarily dispute whether a person of skill would have been motivated to combine bupropion and naltrexone with reasonable expectation of success. Federal Circuit held that, given that both drugs had shown weight loss effects, a person of ordinary skill would have been motivated to combine them. A person of skill would have understood that a combination for reducing weight gain and decreasing carbohydrate cravings may affect weight loss as well. Nalpropion argued that bupropion does not possess sufficient weight loss efficacy to obtain FDA approval by itself. Therefore, a person of skill would not have been motivated to develop bupropion for weight loss. Federal Circuit, however disagreed & said that “[t]here is no requirement in patent law that the person of ordinary skill be motivated to develop the claimed invention based on a rationale that forms the basis for FDA approval.” Allergan, Inc. v. Sandoz Inc., 726 F.3d 1286, 1292 (Fed. Cir. 2013). “Motivation to combine may be found in many different places and forms; it cannot be limited to those reasons the FDA sees fit to consider in approving drug applications.” Also, every limitation in the claims at issue was met by O’Malley and Jain. Federal Circuit finally rejected objective indicia of nonobviousness & reversed the district court’s holding that these claims are not invalid.

Thus, Federal Circuit affirmed written description decision & reversed non-obviousness decision of district court.

Dissent:

Chief Judge, Prost in dissent criticized the “substantially equivalent” test for written description requirement. She said that based on her understanding of this court’s precedent, she would find claim 11 of the ’195 patent invalid for lack of adequate written description. She essentially differed in 3 aspects: First, the USP 2 clause is limiting. Second, the majority’s “substantially equivalent” rule is inconsistent with this court’s precedent. Third, the district court clearly erred in finding that the ’195 patent’s written description includes a disclosure “substantially equivalent” to USP 2.

Cabazitaxel - USA

On Aug 14, 2019, Federal Circuit affirmed-in-part & vacated-in-part district court’s decision regarding Jevtana® compound & method of use patent.

This appeal concerns Sanofi’s patent US  5,847,170 & US 8,927,592. The US’ 170 patent claims cabazitaxel compound & US’ 592 patent claims method of treatment of prostate cancer with cabazitaxel. Defendants (Fresenius, Dr Reddy’s lab, Sandoz, Accord, Apotex, Actavis & Mylan) filed ANDA with USFDA to market generic version of Jevtana®. Sanofi sued defendants under Hatch-Waxman regulation for infringement.While the litigation was pending some defendants challenged US’592 in PTAB. After oral hearing PTAB found claim 1-5 & 7-30 invalid as obvious. PTAB also denied Sanofi’s motion to amend the claims. Sanofi then disclaimed claims 7, 11, 14–16, 26 and informed the district court accordingly. But district court still ruled that disclaimed are invalid. Sanofi appealed because as per them there was no case or controversy as claims were cancelled. Defendants cross-appealed & took position that there was case or controversy & district court did not err. Defendants also appealed district court’s decision which found claims 1-2 of US’170 valid.

a. Appeal regarding case or controversy - 

On appeal, Sanofi argues that after it disclaimed the particular claims, there was no longer a case or controversy regarding those claims, and the district court thus lacked authority to invalidate them. Defendants responded that there may still have been a case or controversy over the disclaimed claims depending on the merits of their potential future issue or claim preclusion defense, which Defendants could raise if Sanofi succeeds in amending claims of the ’592 patent & then asserts the amended claims against Defendants.

Federal Circuit said that Article III empowers federal courts to adjudicate only “Cases” and “Controversies.” To satisfy the case or controversy requirement in the declaratory judgment context, the parties’ dispute must be “‘real and substantial” rather than mere hypothetical state of facts. Further, “an actual controversy must be extant at all stages of review, not merely at the time the complaint is filed. When Sanofi disclaimed the disclaimed claims, it “effectively eliminated those claims from the . . . patent,” Vectra Fitness, Inc. v. TNWK Corp., 162 F.3d 1379, 1383 (Fed. Cir. 1998), leaving the ’592 patent “as though the disclaimed claim(s) had ‘never existed,’” Genetics Inst., LLC v. Novartis Vaccines & Diagnostics, Inc., 655 F.3d 1291, 1299 (Fed. Cir. 2011). Defendants here point to no such concrete and realistic threat created by the effectively nonexistent disclaimed claims. Therefore, Defendants’ reliance on Teva [Teva Pharmaceuticals USA, Inc. v. Novartis Pharmaceuticals Corp., 482 F.3d 1330 (Fed. Cir. 2007)] is misplaced.

Defendants further alleged that if court vacates the district court’s judgment of invalidity of the disclaimed claims, then Defendants will lose the possible benefit of an issue preclusion defense based on that judgment should Sanofi obtain amended claims and assert them against Defendants. Federal Circuit, however, concluded that this alleged injury did not provide a case or controversy at the time of the court’s judgment. Because the relevance of the disclaimed claims to a possible issue preclusion defense was merely speculative. Second, even assuming that Defendants’ stake in the district court’s judgment concerning the disclaimed claims was sufficiently imminent, they have not established that the judgment pertaining to those claims is material to a possible future suit. Defendants have not shown the existence of a case or controversy over the disclaimed claims at the time the district court entered judgment. The district court thus lacked authority & therefore Federal Circuit vacated court’s judgment with respect to disclaimed claims.

b. Appeal regarding validity of claims 1 & 2 of US’170 –

                                                [Fig: https://ejhp.bmj.com/content/22/5/260]

Defendants’ cross-appealed from the district court’s judgment that cabazitaxel, claimed in claims 1 and 2 of the ’170 patent, would not have been obvious over docetaxel, which has been determined to be the lead compound and, in effect here, the closest prior art.  Defendants argued at the district court that a skilled artisan would have been motivated to increase the lipophilicity of docetaxel to interfere with a protein called Pgp to thwart drug resistance & therefore, would have made replacement at C7 & C10 position with methoxy group. Sanofi responded that Defendants’ obviousness theory was hindsight-driven and that the district court did not err in rejecting it.

Federal Circuit said that district court made no error as in finding that prior art references, Hait and Lampidis would not have provided a reason to make docetaxel more lipophilic. Because, these references not contemplate taxanes, they investigated compounds that are structurally very different from taxanes. Even assuming there was some general motivation to make docetaxel more lipophilic to combat drug resistance, the district court also did not clearly err in finding that Defendants failed to establish a motivation to do so by specifically making simultaneous methoxy substitutions at C7 and C10. Taxane researchers investigated substitutions at many positions (C2, C3′, C7, C9, and C10), and the voluminous references in this case support that finding. Despite the apparent interest in taxane analogs, not a single reference relied on by Defendants made simultaneous substitutions of any kind at C7 and C10. And of the references that made individual methoxy substitutions at C7 or C10, none tested those taxane analogs against drug resistant cell lines or taught that the analogs would overcome drug resistance. Defendants reference-specific arguments are emblematic of hindsight reasoning.

Thus, Federal Circuit agreed with Sanofi that the district court correctly concluded that claims 1 and 2 of the ’170 patent would not have been obvious over docetaxel.

Weekly Patent Litigation Roundup

Amgen Wins Patent Case On Enbrel® (etanercept)

THOUSAND OAKS, Calif., Aug. 9, 2019 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. District Court for the District of New Jersey has ruled in Amgen's favor on validity of the two patents that describe and claim Enbrel® (etanercept) and methods for making it. Amgen affiliates Immunex Corporation and Amgen Manufacturing, Limited, along with the owner and licensor of the two patents, Hoffmann-La Roche Inc., brought the patent infringement action in Federal Court against Sandoz Inc., Sandoz International GmbH and Sandoz GmbH (together, Sandoz). Before trial, Sandoz acknowledged that its biosimilar etanercept infringes seven patent claims in U.S. Patent Nos. 8,063,182 and 8,163,522. Trial proceeded only on Sandoz's challenges to validity of those claims. After careful consideration, the Court found that Sandoz had not met its burden to prove all seven asserted claims invalid.…

https://www.biospace.com/article/releases/amgen-wins-patent-case-on-enbrel-etanercept-/

Novartis Pharma A.G., Novartis Pharmaceutical AG and Novartis AG v. TEVA Nederland B.V., District Court The Hague, The Netherlands, Judge in Interlocutory Proceedings, 5 July 2019, Case No. ECLI:NL:RBDHA:2019:7792

Teva holds a Dutch marketing authorization for the generic version of everolimus, named Everolimus Teva. In the SmPC and and the Patient Information Leaflet of Everolimus Teva, it is stated that everolimus in combination with exemestane is indicated for the treatment of hormone receptor positive advanced breast cancer. Novartis invokes EP 603 and EP 246 and requests an injunction against Teva for medicines containing everolimus that are indicated for hormone receptor positive advanced breast cancer, or -alternatively-, that Teva is ordered to remove the indication hormone receptor positive advanced breast cancer from the marketing authorization. The injunction is denied as the PI judge rules that there is a real and serious chance that the invoked patents will be held invalid in proceedings on the merits (or in opposition / appeal proceedings at the EPO) as it is sufficiently plausible that the man skilled in the art would have tried the combination of everolimus and exemestane / aromatase inhibitor with the expectation that this would work in treating breast cancer…

http://eplaw.org/nl-novartis-v-teva-2/

Gilead loses key patent claims for Sovaldi in China, opening door to earlier generic entry

A partial patent invalidation by Chinese authorities has shaken the case Gilead has been building for its hep C star Sovaldi by removing a key barrier to generic entry. The decision means knockoffs of the highly effective hep C treatment can arrive as early as next year — rather than 2024, when the patent was originally set to expire — according to the Initiative for Medicines, Access, and Knowledge, or I-MAK. I-MAK filed one of the two requests for patent invalidation cited in the ruling, together with Chinese drugmaker Fujian Cosunter Pharma.…

https://endpts.com/gilead-loses-key-patent-claims-for-sovaldi-in-china-opening-door-to-earlier-generic-entry/

Akebia Therapeutics® Announces Settlement of Auryxia® Patent Litigation with Par Pharmaceutical

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Akebia Therapeutics, Inc. (Nasdaq: AKBA), today announced that its wholly-owned subsidiary, Keryx Biopharmaceuticals, Inc., and its licensor Panion & BF Biotech, Inc., have entered into a Settlement and License Agreement (Agreement) with Par Pharmaceutical, Inc., an Endo International company (Par). This settlement resolves patent litigation brought by Keryx and Panion in response to Par’s Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of Auryxia (ferric citrate) tablets prior to the expiration of the applicable patents. Pursuant to the terms of the Agreement, the companies will grant Par a license to market its generic version of Auryxia in the United States beginning on March 20, 2025 (subject to U.S. FDA approval), or earlier under certain circumstances customary for settlement agreements of this nature…

https://www.businesswire.com/news/home/20190805005226/en/Akebia-Therapeutics%C2%AE-Announces-Settlement-Auryxia%C2%AE-Patent-Litigation

Allergan to pay $2.7m to settle antitrust suit over Asacol

A subsidiary of Irish pharmaceutical company Allergan is to pay a combined total of $2.7 million to three organisations that were part of an antitrust class against the drugmaker…

https://www.lifesciencesipreview.com/news/allergan-to-pay-2-7m-to-settle-antitrust-suit-over-asacol-3634

Alkermes Grants Amneal Generic Rights for Vivitrol

Irish drugmaker Alkermes has entered into a settlement and license agreement with American generics company Amneal in order to end the generics maker’s inter partes review of a Vivitrol (naltrexone for extended-release injectable suspension) patent. The deal wraps up Amneal’s challenge of the patent and grants the company the non-exclusive right to manufacture and market a generic version of the narcotic and alcohol addiction treatment in the U.S. “sometime in 2028 or earlier under certain circumstances,” Alkermes said. While there are additional terms to the agreement, they remain confidential. Alkermes’ patent in question is set to expire in 2029.…

https://www.fdanews.com/articles/192221-alkermes-grants-amneal-generic-rights-for-vivitrol

Pemetrexed - USA

On Aug 09, 2019, Federal Circuit affirmed district court’s decision that Hospira & Dr Reddy’s Lab.(DRL) infringed methof of administration patent under doctrine of equivalents.

This appeal concerns Eli Lilly’s patent US 7,772,209. The ‘209 patent claims method of administering pemetrexed disodium for the treatment of cancer along with vitamin B12 & folic acid. Lilly markets the compound pemetrexed in the form of a disodium salt as Alimta®, which is indicated, both alone and in combination with other active agents, for treating certain types of non-small cell lung cancer and mesothelioma. Hospira & DRL (Defendants) filed NDA with USFDA to market the product with different salt, ie pemetrexed ditromethamine. Lilly sued both the companies under Hatch-Waxman regulation for infringement of US’ 209. Delaware court after trial held that pemetrexed ditromethamine product infringes the said patent under doctrine of equivalents (DOE). Additionaly, district also found that Hospira infringed under literal infringement. Both defendants appealed.

a. Literal infringement by Hospira’s product:

Hospira on appeal argued that it cannot literally infringe the claims of the ’209 patent because intravenous administration of pemetrexed ditromethamine dissolved in saline—a solution which contains pemetrexed and chloride anions alongside sodium and tromethamine cations—is not “administration of pemetrexed disodium.” Lilly counters that Hospira’s view improperly imposes a “source limitation,” requiring that the pemetrexed disodium salt exist in solid form before administration, even thoufh its label requires administration of solution. Federal circuit however, sided with Hospira & held that product administered is ditromethamine. When it goes into solution various ions are formed such as pemetrexed, sodium,c hloride & tromethamine. But solution containing these ions cannot be deemed pemetrexed disodium simply because some assortment of the ions in the solution consists of pemetrexed and two sodium cations. Therfore to infringe the claim literally, the pemetrexed disodium salt must be itself administered. Once into solution, pemetrexed disodium is not remains present as salt, so the ditromethamine. Therefore, it does not infringe under literal infringement.

b. Prosecution History Estoppel (PHE) –

On appeal defendants argued that district court erred in determining infringement under DOE because PHE applies here. Defendants conteded that, Plaintiff during prosecution limited claims from antifolate to specific pemetrexed disodium in view of the prior arts. In response, Lilly relies on only one exception to giving effect to the presumption as to the scope of surrender: that the rationale of its amendment “[bore] no more than a tangential relation to the equivalent in question.”

Federal Circuit agreed with Lilly & said that defendants view of prosecution history estoppel, and the tangential exception in particular, too rigid. Plaintiff narrowed claims because of the other antifolate (methotrexate) mentioned in the prior art & not because of salts. Methotrexed was mentioned in the prior art & therefore to remove this rejection, claimes were amended to pemetrexed disodium salt from anitfolate. The particular type of salt to which pemetrexed is complexed relates only tenuously to the reason for the narrowing amendment, which was to avoid prior art reference. Therefore, based onprosecution history it is concluded that Lilly’s amendment was merely tangential to pemetrexed ditromethamine. Thus, PHE cannot apply.

c. Disclosure-dedication rule –

Defendants argued that ditromethamine was mentioned in the one prior art which appeared in the specification. Therefore by not claiming the ditromethamine, plaintiff surrendered the claim scope for ditromethamine. But, Federal CIruit said that the prior art reference was not incorporated entirely in the specification. Moreover, there were generic structures disclosed in the reference which essentialy covers thousands of compound. Though it mentions amine salt in general  but there was no specific disclosure of pemetrexed ditromethamine. Therefore skilled person could not envision that ditromethamine was disclosed & dedicated to public.

d. Insubstantial difference test -

Defendants argued that that the district court erred in finding that its proposed pemetrexed ditromethamine product will be administered in an insubstantially different way from the claimed method. There are substantial differences between them, therefore they are not equivalents. But Federal circuit held that the activity of compound is because of pemetrexed ion & not because of salts. Therefore when both the salts go into the solution, both forms pemetrexed ions. Thus, chemical differences between sodium and tromethamine are clinically irrelevant because each undisputedly lacks therapeutic activity.

In summary, Federal Circuit concluded that neither prosecution history estoppel nor the disclosure-dedication rule bars Lilly from asserting infringement through equivalence.

Asenapine - USA

On Aug 06, 2019, Delaware court denied each motion filed by Forest & Sigmapharm to enter final judgment after trial based on a post-trial amendment to ANDA specification.

The current controversy in this ongoing Hatch-Waxman case involves a motion by defendant Sigmapharm to vacate a finding of infringement pursuant to Fed. R. Civ. P. 60(b) based on a post-trial amendment to its ANDA. Plaintiffs Forest oppose Sigmapharm’s motion and filed a cross motion to enter final judgment.

During litigation Forest asserted that the defendants infringed claim 1 of U.S. Patent No. 5,763,476; which requires that the pharmaceutical composition “disintegrate within 30 seconds in water at 37° C.”

Sigmapharm’s first ANDA, filed in August 2013, had a disintegration specification of “not more than 5 minutes”—Specification 1. In August 2015, the FDA issued a Complete Response, rejecting Specification 1 because the disintegration time was not “within seconds” as required by the Reference Listed Drug (RLD).

One month later, in February of 2016, Sigmapharm responded to the FDA’s rejection of Specification 1 by amending its disintegration specification to “not more than 75 seconds”—Specification 2.

In May 2016, three months before trial was scheduled to start before Judge Robinson, Sigmapharm again amended its disintegration specification from “not more than 75 seconds” to “35 to 75 seconds”—Specification 3.

In September 2016, the FDA rejected Sigmapharm’s Specification 3, reiterating its recommendation that Sigmapharm reformulate its drug product so that it demonstrated “a disintegration time that is in-line with the labeling requirement of ‘within seconds.’” On October 13, 2016, Judge Robinson granted Forest’s request and trial on infringement as to Sigmapharm was stayed & to be proceeded with other defendants.

In response to the FDA’s September 2016 Complete Response, Sigmapharm again amended its disintegration specification in March 2017—Specification 4.  Sigmapharm changed the single disintegration test to two separate tests and lowered the upper time limit to under a minute. Thus, the “35 seconds to 75 seconds” became:

(1) at 30 seconds “fail” USP <701> (the “30-Second Test”), and

(2) at 55 seconds “pass” USP <701> (the “55-Second Test”).

On Nov 16, 2018, Court issued a post-trial opinion finding that Sigmapharm literally infringed claim 1 of the ’476 patent. Court found that Sigmapharm’s product “disintegrate within 30 seconds in water at 37° C.” based upon the testimony of Forest’s expert, Dr. Adam Myers, who, based upon testing consistent with USP <701>, opined that Sigmapharm’s Specification 4 infringed Claim 1. 

Sigmapharm took the position that the two disintegration tests in Specification 4—the 30-Second Test and the 55-Second Test—precluded infringement. Sigmapharm equated “failing” USP <701> with proof that a batch of tablets would not disintegrate within 30 seconds. But court rejected this approach as it was not consistent with the “words of the claim(s).” Court found that a “fail” result would unreliably allow too many tablets to disintegrate within 30 seconds to conclusively show that a batch would not disintegrate within that time.

After this opinion, instead of submitting a proposed form of final judgment, Sigmapharm amended its ANDA by adopting - Specification 5, and filed a motion pursuant to Fed. R. Civ. P. 60(b) asking court to change infringement finding to non-infringement and enter final judgment in its favor. According to Sigmapharm, Specification 5 changed the acceptance criteria under Sigmapharm’s 30-Second Test such that a batch of its tablets would not disintegrate within 30 seconds. In other words, Sigmapharm now posits no more than 0/6 tablets will disintegrate within 30 seconds on stage 1 and 2/18 tablets on stage 2.  According to Sigmapharm, the FDA approved Specification 5 by default.

Sigmapharm sought relief from judgment pursuant to Fed. R. Civ. P. 60(b)(2), 60(b)(5), and 60(b)(6).

Court denied motion under Rule 60(b)(2) because  as per this rule “newly discovered evidence is evidence of facts should be in existence at the time of trial”. Here Specification 5 was not in existence at the time of trial. Instead, Sigmapharm created Specification 5 after trial, in response to court’s finding of infringement.

Court denied motion under Rule 60(b)(5) because this rule only “provides for relief from injunction or consent decrees.” Here, Sigmapharm is not seeking modification to an injunction or consent decree, but a change to legal conclusions. Accordingly, Rule 60(b)(5) is not the proper grounds to grant the relief Sigmapharm seeks.

Court also denied motion under Rule 60(b)(6) because Sigmapharm failed to show that it is an exceptional circumstances.

Court said that the “Ferring” [Ferring B.V. v. Watson Laboratories, Inc., 764 F.3d 1382 (Fed. Cir. 2014)] case cited by Sigmapharm is entirely distinguishable from the facts before it. First, unlike in Ferring, court’s finding of infringement was not based solely on the ANDA, but also on actual testing of Sigmapharm’s generic product. Second, there was no discussion at the trial before court suggesting that Sigmapharm would or should amend its ANDA to moot the issue of infringement. Third, the Ferring court found no prejudice because, among other reasons, Ferring never requested that the district court reopen the record to address infringement by the amended ANDA.

Thus court declined to enter a final judgment in Sigmapharm’s favor based on Specification 5.

Court also declined to enter a final judgment in Forest’s favor based on Specification 4 because Specification 4 is no longer operative now. In addition, Sigmapharm asserts that, due to the changes made by Specification 5, “[t]he batches tested by [Forest], some of which were found to infringe, are no longer representative, in terms of disintegration characteristics, of the products that Sigmapharm will manufacture and market.” Court further said that nothing precludes it from disregarding Specification 5 and entering final judgment as to Specification 4 based on the findings set forth in the November 18, 2018 trial opinion. But if Sigmapharm wants the opportunity to prove that Specification 5 does not infringe the ’476 patent,  court willing to provide that opportunity.

Therefore, Sigmapharm has two options:

(1) have a final judgment entered based on the November 16, 2018 opinion addressing Specification 4 and appeal that judgment to the United States Court of Appeals for the Federal Circuit, or

(2) request that court reinstate the discovery and litigation process with respect to Specification 5.

Tiotropium - EPO

EPO opposition / appeal decision:

Case number	Decision date	Online available	Patentee	Opponent(s)	Patent No.	Final Decision
T 1837/16	Jun 18, 2019	Aug 06, 2019	Boehringer Ingelheim	Teva / Actavis / Vossius & Partner	EP1496858	The appeal is dismissed

EP1496858 B1 (Forward pharma; Exp: Apr 02, 2023):

1. Inhalation kit consisting of an inhaler and an inhalable powder containing tiotropium in an amount of 0.001 to 5 %, in admixture with a physiologically acceptable excipient with an average particle size of between 10 to 500 µm, wherein the inhaler comprises a housing, containing two windows, a deck in which there are air inlet ports and which is provided with a screen secured via a screen housing, an inhalation chamber connected to the deck on which there is a push button provided with two sharpened pins and movable counter to a spring, a mouthpiece which is connected to the housing, the deck and a cover via a spindle to enable it to be flipped open or shut, and three holes with diameters below 1 mm in the central region around the capsule chamber and underneath the screen housing and screen, and further characterized in that the said inhaler displays a flow resistance of about 0.01 - 0.1 kPa min / l.

5. Inhaler suitable for the administration of an inhalable powder containing tiotropium in an amount of 0.001 to 5 %, in admixture with a physiologically acceptable excipient with an average particle size of between 10 to 500 µm, said inhaler comprises a housing, containing two windows, a deck in which there are air inlet ports and which is provided with a screen secured via a screen housing, an inhalation chamber connected to the deck on which there is a push button provided with two sharpened pins and movable counter to a spring, a mouthpiece which is connected to the housing, the deck and a cover via a spindle to enable it to be flipped open or shut, and three holes with diameters below 1 mm in the central region around the capsule chamber and underneath the screen housing and screen, and further characterized in that said inhaler displays a flow resistance of about 0.01 - 0.1 kPa min / l .

Summary: The patent was opposed under Article 100 (a), (b), (c) EPC on the grounds that its subject-matter lacked novelty and inventive step, was not sufficiently disclosed, and extended beyond the content of the application as filed.

The appeal lies from the decision of the opposition division to revoke the patent. The decision was based on the claims as granted as main request and 5 sets of claims filed as auxiliary requests 1 and 2 with letter of 26 February 2016, and filed during the oral proceedings of 28 April 2016 as auxiliary requests 3,4 and 5.

Epinephrine - USA

IPR decision: Aug 02, 2019

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	Decision
IPR2019-01021	04/26/2019	--	Adamis Pharma	9,283,197	Belcher Pharma	Terminated-Settled

US 9,283,197 (Taneja; Jugal K.; Exp: 08/15/2034) – OB listed

1. A liquid pharmaceutical formulation of preservative-free and sulfite-free, 1 mg per mL l-epinephrine sterile solution for uses including injection; said liquid pharmaceutical formulation having a pH between 2.8 and 3.3; said liquid pharmaceutical formulation compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine, and further including a tonicity agent; said liquid pharmaceutical formulation having no more than 6.5% total impurities at release, including no more than 6% d-epinephrine and no more than 0.5% adrenalone, and no more than 12.5% total impurities over a shelf-life of at least 12 months, including no more than 12% d-epinephrine and no more than 0.5% adrenalone; said liquid pharmaceutical formulation stored in a container with an inert gas prior to use.

4. A liquid pharmaceutical formulation of preservative-free and sulfite-free, 1 mg per mL l-epinephrine sterile solution for uses including injection; said liquid pharmaceutical formulation having a pH between 2.8 and 3.3; said liquid pharmaceutical formulation compounded as 1.0 to 1.06 mg/mL l-epinephrine, along with 8.6 mg/mL sodium chloride as the tonicity agent, 7.26 mg/mL of 1 Normal hydrochloric acid as the dissolution agent, 987.11 mg/mL water for injection as a solvent, and with additional hydrochloric acid to adjust pH; said liquid pharmaceutical formulation having less than 6.5% total impurities at release, including less than 6% d-epinephrine and less than 0.5% adrenalone, and less than 12.5% total impurities over a shelf-life of at least 12 months, including less than 12% d-epinephrine and less than 0.5% adrenalone.

6. An injectable liquid pharmaceutical formulation of l-epinephrine sterile solution; said liquid pharmaceutical formulation having a pH between 2.8 and 3.3; said injectable liquid pharmaceutical formulation compounded in an aqueous solution as 1.0 to 1.06 mg/mL l-epinephrine, and further including a tonicity agent; said liquid pharmaceutical formulation including no more than about 6% d-epinephrine and no more than about 0.5% adrenalone at release, and no more than about 12% d-epinephrine and no more than about 0.5% adrenalone over a shelf-life of at least 12 months.

Budesonide - USA

Claim Construction (District of Delaware): Aug 02, 2019

Plaintiffs Valeant Pharmaceuticals International, Salix Pharmaceuticals Ltd., and Cosmo Technology Ltd. ("Plaintiffs") filed suit against Actavis Laboratories Fl., Inc., Actavis Pharma Inc., Teva Pharmaceuticals USA Inc., and Teva Pharmaceutical Industries, Ltd. ("Defendants") on August 22, 2018, alleging infringement of U.S. Patent Nos. 10,052,286; 10,064,878; 10,105,374; 10,143,698; 10,154,964  and 10,172,799 (collectively "the patents-in-suit"). These patents claim "controlled release budesonide formulations with a tablet core inside a gastroresistant coating."

Consolidated claim construction briefing was submitted on June 17,2019, an amended version was filed on June 27,2019, and the Court held a claim construction hearing on July 2, 2019.

Construction of Disputed Terms:

1. "Matrix":

Plaintiffs: "a structure for controlling the release of an active ingredient that does not have layers"

Defendants: "a homogeneous structure in all its volume"

Court: "a homogeneous structure in all its volume"

2. "Mixture" and "Compressed Blend"

Plaintiffs: "a composition of two or more substances that have been mixed" and

"a composition of two or more substances that have been mixed and compressed"

Defendants: "a homogeneous composition of two or more substances" and

"a compressed matrix (or homogeneous structure in all its volume)"

Court: "a homogeneous composition of two or more substances" and

"a compressed matrix (or homogeneous structure in all its volume)"

3. "Pharmacokinetic terms

The Court will adopt the parties' stipulated constructions for the "pharmacokinetic terms."

Claim term	Court’s construction
"an AUCo-infinity of said budesonide in   said human of about 16431.2±1 0519.8(pg)x(h)/mL" and "an AUC of said budesonide in said human of about 16.43 ±10.52 (ng)x (h)lmL"	"an AUCO-infinity of said budesonide in said human of approximately 16431.2±10519.8 (pg)x(h)/mL, i.e. approximately between 5,911.4 (pg)x(h)/mL and approximately 26,951 (pg)x(h)/mL" and "an AUC of said budesonide in said human of approximately 16.43±10.52 (ng)x(h)/mL, i.e. between approximately 5.91 (ng)x(h)/mL and approximately 26.95 (ng)x(h)/mL"
"a Cmax of said budesonide in said human of about 1348.8±958.8 pg/mL" and "a Cmax of said budesonide in said human of about 1.35±0.96 ng/mL"	"a Cmax of said budesonide in said human of approximately 1348.8±958.8 pg/mL, i.e. between approximately 390 pg/mL and approximately 2307.6 pg/mL" and "a Cmax of said budesonide in said human of approximately 1.35±0.96 ng/mL, i.e. between approximately 0.39 ng/mL and approximately 2.31 ng/mL"
"a T max of said budesonide in " said human of about 13.3±5.9 hour[s]"	“a T max of said budesonide in said human of approximately 13.3±5.9 hours, i.e. between approximately 7.4 hours and approximately 19.2 hours"
“oral administration of the oral dosage form to a human" and "oral administration of the tablet to a human"	"No constructions necessary”
"said human"	“No construction necessary”

4. "Controls the release kinetics

Plaintiffs: Plain and ordinary meaning, i.e. "controls the release kinetics"

Defendants: "controls the release kinetics without effects from physically discrete elements"

Court: Plain and ordinary meaning, i.e. "controls the release kinetics"