2018 Updates To IPR Practice For Orange Book Listed Patents

Transcription

1 2018 Updates To IPR Practice For Orange Book Listed Patents Grant Shackelford Sughrue Mion, PLLC

2 Agenda IPR Statistics At The PTAB Recent FWDs of Orange Book listed patents Updates on IPR Practice Change of Claim Construction Standard Saint Regis Mohawk Tribe, Allergan: Tribal Immunity Hatch-Waxman Integrity Act of

3 USPTO Study On Orange Book-Listed Patents 1. What Are the Filing Trends for Petitions Challenging Orange Book-listed Patents? 2. How Does the Institution Rate on Petitions Challenging Orange Book-listed Patents Compare to Those of Other Technologies? 3. What Are the Outcomes of Challenges to Orange Book-listed Patents? 3

4 Overall Filing Trends 4

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6 Institution Rate Comparison Through November 2018: Non-Orange Book: 67% instituted Orange Book: 65% instituted Data collected from DocketAlarm 6

7 IPR Targeted Patents 198 Orange Book-listed patents challenged in IPRs between September 16, 2012-April 24, designated as active ingredient patents 87 designated as formulation patents 26 designated as both 78 designated as neither 38 fully successful IPR challenges: 25 Orange Book-listed patents 2 active ingredient patents 7 formulation patents 16 neither Darrow et al., The Generic Drug Industry Embraces a Faster, Cheaper Pathway for Challenging Patents, APPLIED HEALTH ECONOMICS AND HEALTH POLICY (Aug. 24, 2018). 7

8 Grounds Of Unpatentability ( ) Institution Decisions Obviousness under grounds were instituted 201 grounds are denied Anticipation under grounds were instituted 27 were denied Final Written Decisions Obviousness: 74 grounds claims unpatentable 60 grounds claims upheld Anticipation: 4 grounds claims unpatentable 0 grounds claims upheld Lex Machina, 2018 Hatch-Waxman ANDA Litigation Report 8

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11 Orange Book Patents in ANDA vs. PTAB ( ) ANDA Litigation Cases terminated in 2016 and settled (50%) 155 dismissed for procedural reasons 208 cases Plaintiff won (25%) 62 cases Defendant won (7%) Judgment Events: Infringement 158 No Infringement 68 Invalidity 30 No Invalidity 124 Unforceability 1 No Unenforceability 73 PTAB Trials completed in 2016 and settled (23%) 26 dismissed for procedural reasons 80 trials Patent Owner won (41%) 42 trials Petitioner won (22%) Denied institution: 49 All claims upheld: 31 All claims unpatentable: 37 (19%) All claims amended: 1 Claims disclaimed: 4 Lex Machina, 2018 Hatch-Waxman ANDA Litigation Report 11

12 Takeaways IPR institution rate for Orange Book patents is about the same as all other technologies (65%) Formulation and method of treatment claims are the primary targets of IPR petitions FWDs that invalidate all claims are fewer for Orange Book patents (46%) than all other technologies (66%) PTAB trials of Orange Book-listed patents result in unpatentability more often than invalidity in ANDA litigation 12

13 2018 Final Written Decisions 13

14 2018 Final Written Decisions Parties IPR No. U.S. Pat. No. Type of Claims Result Par Pharma v. Novartis Amerigen et al.v. Janssen Mylan et al. v. Janssen Wockhardt v. Janssen Amneal v. Purdue Amneal v. Purdue IPR ,665,772 Compound No claims unpatentable IPR ,822,438 Method of treatment IPR ,822,438 Method of treatment IPR ,822,438 Method of treatment All claims unpatentable All claims unpatentable All claims unpatentable IPR ,060,976 Formulation All claims unpatentable IPR ,060,976 Formulation All claims unpatentable 14

15 2018 Final Written Decisions Parties IPR No. U.S. Pat. No. Type of Claims Result Luye v. Alkermes IPR ,667,061 Formulation No claims unpatentable Koios v. Medac IPR ,664,231 Method of treatment Acrux v. Kaken IPR ,214,506 Method of treatment Apotex v. Novartis Argentum v. Alcon Apotex v. OSI Pharmaceutical IPR ,187,405 Method of treatment No claims unpatentable All claims unpatentable No claims unpatentable IPR ,268,299 Formulation No claims unpatentable IPR ,900,221 Method of treatment All claims unpatentable 15

16 Koios Pharmaceuticals v. MEDAC gmbh (IPR ) 1. A method for the treatment of inflammatory autoimmune diseases in a patient in need thereof, comprising subcutaneously administering to said patient a medicament comprising methotrexate in a pharmaceutically acceptable solvent at a concentration of more than 30 mg/ml. 16

17 Koios Pharmaceuticals v. MEDAC gmbh [A] prior art reference in order to anticipate under 35 U.S.C. 102 must not only disclose all elements of the claim within the four corners of the document, but must also disclose those elements arranged as in the claim. [I]t is not enough that the prior art reference includes multiple, distinct teachings that the artisan might somehow combine to achieve the claimed invention. Net MoneyIn Inc. v. Verisign, Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008). 17

18 Grint disclosures: General disclosure that methotrexate is generally present in from about 0.1 to about 40 mg/ml of carrier, Example 1 study in which a mg/week dose of methotrexate was given to rheumatoid arthritis patients by oral, subcutaneous, or intramuscular administration. Concentration not specified 18

19 Anticipation by Grint: A POSA would recognize that different concentrations of methotrexate are used for the different forms of administration Broad concentration range would not apply to all dosage forms Evidence established that the conventional concentration of methotrexate for treating rheumatoid arthritis via subcutaneous administration was 25 mg/ml or less; no citation to a higher concentration No link between the high concentration range and subcutaneous administration. 19

20 Wyeth s disclosure: Wyeth is a pharmaceutical label for lyophilized injection products available in 20 mg (reconstituted to 25 mg/ml or less) and 1 gram vials (reconstituted to 50 mg/ml). Discloses treating rheumatoid arthritis by subcutaneous injection Discloses administering large dosages for treating cancer and small dosages for treating autoimmune diseases No linkage between the 50 mg/ml form and subcutaneous administration to treat rheumatoid arthritis 20

21 Luye Pharma v. Alkermes Pharma (IPR ) 1. A composition suitable for injection through a needle into a host, comprising: microparticles comprising a polymeric binder; and an injection vehicle, wherein said microparticles are suspended in said injection vehicle at a concentration of greater than about 30 mg/ml to form a suspension, wherein a fluid phase of said suspension has a viscosity greater than about 20 cp and less than about 600 cp at 20 C., wherein the viscosity of said fluid phase of said suspension provides injectability of the composition through a needle ranging in diameter from gauge. 21

22 Inherency Johnson 3% CMC, 1% polysorbate 20, 0.9% sodium chloride Viscosity: unknown 061 Patent Vehicle C 3% CMC, 0.1% polysorbate % saline, Viscosity: 56 cp. Petitioner: Declaration submitted during prosecution of the 061 patent stated that in a prior art composition CMC was the viscosity-controlling component. 22

23 Inherent Obviousness "The limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art. PAR Pharm., Inc., 773 F.3d at Inherency may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient. In re Oelrich, 666 F.2d 578, 581 (CCPA 1981). 23

24 Patent Owner s testing data showed that viscosity varies between types of CMC each of these Ashland CMCs yielded a Johnson vehicle with a viscosity below 20 cp when measured at 20ºC and thus fall outside the range claimed in the 061 patent. ([Ex. 2059] 12.) 24

25 Technical literature showed that viscosity varies within and between grades of CMC Viscosity: various grades of carboxymethylcellulose sodium are commercially available which have differing aqueous viscosities; aqueous 1% w/v solutions with viscosities of mpa s ( cp) may be obtained. An increase in concentration results in an increase in aqueous solution viscosity. Viscosities of various grades of carboxymethylcellulose sodium are shown in Table I

26 Luye Pharma Group v. Alkermes Pharma Board: Record evidence shows that the prior art injection vehicle would not necessarily result in viscosities within the claimed range. 26

27 Apotex, Inc. v. OSI Pharmaceuticals (IPR ) 1. A method for the treatment of NSCLC (non small cell lung cancer), pediatric malignancies, cervical and other tumors caused or promoted by human papilloma virus (HFV), Barrett s esophagus (pre-malignant syndrome), or neoplastic cutaneous diseases in a mammal comprising administering to said mammal a therapeutically effective amount of a pharmaceutical composition comprised of at least one of N-(3- ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine [erlotinib], or pharmaceutically acceptable salts thereof in anhydrous or hydrate forms, and a carrier 27

28 Apotex, Inc. v. OSI Pharmaceuticals OSI's SEC 10-K filing: "With its collaborative partner Pfizer, OSI has focused since 1986 on the discovery and development of novel classes of orally active, molecularly targeted, small molecule anticancer drugs based on oncogenes and tumor suppressor genes and the fundamental mechanisms underlying tumor growth. The first of these programs to yield a clinical candidate, [erlotinib], which targets a variety of cancers including ovarian, pancreatic, nonsmall cell lung and head and neck, achieved a significant milestone with the completion of Phase I safety trials and the initiation of Phase II clinical trials in the United States in cancer patients. [Erlotinib] is a potent, selective and orally active inhibitor of the epidermal growth factor receptor, a key oncogene in these cancers." 28

29 Apotex, Inc. v. OSI Pharmaceuticals OSI: one of ordinary skill in the art would not have relied on a financial document to find motivation to treat NSCLC one of ordinary skill in the art would not have had any reason to treat NSCLC using erlotinib [g]iven the undisputed lack of data PTAB: Competitor pharmaceutical companies working in the same area as OSI at the time of invention would have been aware of company filings such as OSI s 10-K and would have looked to OSI s 10-K to determine which drugs and treatments pharmaceutical companies were pursuing The lack of data in OSI s 10-K was not critical given the breadth of the challenged claims 29

30 Acrux DDS Pty v. Kaken Pharmaceutical and Valeant Pharmaceuticals (IPR ) 1. A method for treating a subject having onychomycosis wherein the method comprises topically administering to a nail of said subject having onychomycosis a therapeutically effective amount of an antifungal compound represented by [formula (II)] The method of claim 1, in which the compound represented by the formula (II) is [efinaconazole]

31 Acrux DDS Pty v. Kaken Pharmaceutical "nail" The term 'nail' includes nail plate, nail bed, nail matrix, further side nail wall, posterial nail wall, eponychium and hyponychium which make up a tissue around thereof. '506 patent at 4: onychomycosis the express definition of onychomycosis includes superficial mycosis, which in turn is expressly defined as a disease that lies in the skin or visible mucosa. '506 patent at 5:20-26, Sughrue Mion 9: PLLC 31

32 Acrux DDS Pty v. Kaken Pharmaceutical Primary reference discloses efinaconazole as a highly potent antifungal with broad spectrum activity that is not inactivated by keratin Including T. mentagrophytes infections Secondary references teach topical treatment of antifungals to nails to treat onychomycosis. Board: it would have been obvious to combine the references to use the potent efinaconazole agent to treat infections in a nail. 32

33 Apotex v. Novartis (IPR ) 1. A method for reducing or preventing or alleviating relapses in Relapsing-Remitting multiple sclerosis in a subject in need thereof, comprising orally administering to said subject [fingolimod] at a daily dosage of 0.5 mg, absent an immediately preceding loading dose regimen. 33

34 Apotex v. Novartis None of the cited prior art disclosed a daily treatment of fingolimod as low as 0.5 mg without a prior loading dose. PTAB found persuasive prior art submitted by Novartis that taught away from the claimed administration, including that daily doses in that range were substantially less effective in treating MS. 34

35 Janssen Oncology IPRs 1. A method for the treatment of a prostate cancer in a human comprising administering to said human a therapeutically effective amount of abiraterone acetate or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of prednisone. 35

36 Janssen Oncology IPRs Claims obvious in view of primary reference disclosing abiraterone acetate is a more effective CYP17 inhibitor than ketoconazole and secondary reference disclosing administering ketoconazole with prednisone to reduce side effects 36

37 Estoppel from successful IPR? CIVIL ACTIONS AND OTHER PROCEEDINGS. The petitioner in an inter partes review of a claim in a patent... that results in a final written decision... may not assert... in a civil action... that the claim is invalid on any ground that the petitioner raised or reasonably could have raised during that inter partes review. 37

38 Estoppel from successful IPR? "The relevant estoppel provision, 35 U.S.C. 315(e)(2), concededly maybe read in the manner that plaintiffs propose. The manifest statutory intent, however, is to prevent abuse of inter partes proceedings, for example through the withholding of grounds and presentation of serial challenges." "I do not accept, however, that Congress intended to require a party to stand mute in court because it previously prevailed on the same issue before the PTAB." BTG Int'l Ltd. et al. v. Amneal et al., Case No. 2:15-cv-05909, fn. 13 (D.N.J. Oct. 31, 2018) 38

39 No estoppel from successful IPR "The case law contains no deep analysis of the issue, but it appears to reflect the concept that only unsuccessful or unsubmitted arguments are subsequently barred." BTG Int'l Ltd. et al. v. Amneal et al., Case No. 2:15-cv-05909, fn. 13 (D.N.J. Oct. 31, 2018) 39

40 Argentum Pharmaceuticals v. Alcon Research (IPR ) 1. A multi-dose, self-preserved ophthalmic composition, comprising: zinc ions at a concentration of 0.04 to 0.4 mm; and borate and polyol, the borate being present in the composition at a concentration of 0.1 to 2.0% w/v and the polyol being present in the composition at a concentration of 0.25 to 2.5% w/v, the polyol comprising propylene glycol in the composition at a concentration of 0.25 to 1.25% w/v and sorbitol in the composition at a concentration of 0.05 to 0.5% w/v; wherein: (i) the composition has a concentration of anionic species less than 15 mm; and (ii) the composition exhibits sufficient antimicrobial activity to allow the composition to satisfy USP 27 preservative efficacy requirements. 40

41 Petitioner's Formulation A required at least six modifications: 1. replacing BAC with zinc ions; 2. replacing mannitol with sorbitol; 3. adding propylene glycol; 4. adjusting the amounts of zinc ions, sorbitol, and propylene glycol; 5. removing EDTA; and 6. limiting anionic species present in the modified composition to a concentration that is less than 15 mm. 41

42 Par Pharmaceutical v. Novartis AG (IPR ) The '772 patent is directed to derivatives of rapamycin Challenged claims of 1-3 (compound) and 8-10 (method of using the compound) Claims upheld 42

43 Par Pharmaceutical v. Novartis AG Lead compound analysis: 1. Would a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts; 2. Would the artisan have had reason to modify the lead compound to make the claimed compound, with a reasonable expectation of success. 43

44 Proposed modification C-40 Rapamycin 44

45 Par Pharmaceutical v. Novartis AG 1. Selection of Rapamycin as Lead Compound A person of ordinary skill in the art would have recognized the potency of rapamycin Scientists at the time were working to modify rapamycin Beneficial characteristics of other immunosuppressants did not rule out consideration of rapamycin 2. Rationale to Modify Rapamycin to Increase Solubility Rapamycin was known to be minimally soluble Preparation of rapamycin derivatives to improve solubility was "a suitable option from which the prior art did not teach away." Alternative approaches were not so clearly better that rapamycin derivatives would have been ruled out. 3. Reasonable expectation of success of increasing solubility Moderate increases in rapamycin's solubility would significantly improve its utility as a pharmaceutical 45

46 Par Pharmaceutical v. Novartis AG 3. Selection of C40 as the Substitution Site Par: hydroxyl groups have high potential for substitution because their reactions are fundamental and elementary Novartis: no support to narrow to hydroxyl groups; scientists were making substitutions at other locations of the molecule Board: [W]e cannot conclude, as Par contends, that the C40 hydroxyl group would be the obvious, optimal, or preferred location for substitutions to rapamycin. Board: Dr. Jorgensen provides no objective, documentary evidence that would indicate that starting with hydroxyl groups was an accepted rule followed by medicinal chemists in the field. 46

47 Par Pharmaceutical v. Novartis AG 4. Group of Substituents to be Considered The record evidence does not support Par's proposed substitutions (2-hydroxyethoxy group). Shifting technical theories by Par's expert during the IPR "influence the weight that should be given [to his] conclusions in his original Declaration." 47

48 In sum, we find that the person of ordinary skill in the art at the time the invention was made would have been faced with a large number of decision points along the lead compound analysis proposed by Par. The number of potential compounds encompassed by this decision tree is unclear, but would be far larger than the three compounds Dr. Jorgensen discusses. Only by making the right choice at each step would the skilled artisan arrive at everolimus, the compound of claim 10 and the basis of Par s obviousness challenge. In light of these facts, we cannot conclude that the options faced would have been in the words of the Federal Circuit finite, small, or easily traversed. 48

49 IPR Updates Claim Construction Harmonization Proposed Hatch-Waxman Integrity Act of

50 Claim Construction Harmonization The PTAB issued rule changes to alter the claim construction standard in AIA trial proceedings The broadest reasonable interpretation (BRI) claim construction standard will be replaced with the Phillips v. AWH district court standard Applies to petitions filed on or after November 13,

51 Phillips v. BRI: difference mainly in name? Phillips Words of a claim are given their ordinary and customary meaning as understood by a person of ordinary skill in the art so as to be consistent with the specification, of which they are a part Broadest Reasonable Interpretation Words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification and prosecution history. "The broadest reasonable interpretation of a claim term may be the same as or broader than the construction of a term under the Phillips standard. But it cannot be narrower." Facebook, Inc. v. Pragmatus AV, LLC, 582 Fed. Appx. 864, 869 (Fed. Cir. 2014) 51

52 Estoppel effects between PTAB and federal courts Before rule change: A BRI claim construction at the PTAB is not binding on a district court, because the PTAB had not "actually litigated" the issue that would be decided by a subsequent district court construction under the Phillips standard. Skyhawke Technologies, LLC v. Deca International Corp., Case No (Fed. Cir. July 15, 2016) After rule change: prior claim constructions by a court or USITC will be considered. 52

53 THANK YOU! 53