Claim Construction Through Markman: What Constitutes the Active Ingredient?

Transcription

1 SUGHRUE MION LLP Claim Construction Through Markman: What Constitutes the Active Ingredient? Hotel Hilton (Andheri East) Mumbai, India November 13-15, 2018 Hotel Taj Krishna Hyderabad, India November 12-14, 2018 Michael Dzwonczyk Sughrue Mion Sughrue Mion LLP All rights reserved

2 Claim Construction Principles Phillips standard, used in Federal Courts Plain and ordinary meaning applies, consistent with intrinsic evidence Claim language Patent specification Prosecution history Extrinsic evidence ( textbooks, articles, witness testimony, etc.) is subservient to intrinsic evidence Plain and ordinary meaning does not apply when: Patentee provides own definition of claim term in the specification Applicants disclaim or clearly disavow a meaning or claim scope Prosecution history estoppel applies SUGHRUE MION PLLC

3 Claim Construction Principles Effective November 13, 2018, Phillips standard will be used by PTAB in IPR proceedings BRI standard will no longer be used after November 12, 2018 SUGHRUE MION PLLC

4 Latuda (lurasidone) Sumitomo s 372 patent related to novel imide compounds useful as antipsychotic agents Lurasidone is the ( )-enantiomer of an imide compound covered by the '372 patent and the active ingredient in Sunovion's schizophrenia and bipolar depression drug LATUDA Claim 14 is directed to a compound of the formula: SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

5 Latuda (lurasidone) Parties disputed what enantiomers Claim 14 encompassed Generics :"a racemic mixture of two enantiomers of which the structural formula is representative. Sumitomo: "lurasidone, lurasidone's enantiomer, as well as mixtures of these enantiomers. D. Ct. adopted Sumitomo proposal, concluding that the cited extrinsic evidence and prosecution history were irrelevant and/or contradictory to generics construction Generics stipulated to infringement of claim 14 and to the entry of permanent injunctions SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

6 Latuda (lurasidone) On appeal, both parties agree that the structure shown in the claim is the ( )-enantiomer Appellants do not dispute that a person of ordinary skill looking at claim 14's structure in a vacuum would understand it to be one way of depicting the ( )-enantiomer Generics argue that the compound of Claim 14 is identical to Compound 101 in the specification No other description of Claim 14 compound anywhere in spec, by name or structural formula Any construction of Claim 14 is necessarily a construction of compound 101 SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

7 Latuda (lurasidone) Any construction of Claim 14 is necessarily a construction of compound 101 SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

8 Latuda (lurasidone) Examples make clear that compound 101 is an equal mixture of two enantiomers the racemic mixture Examples 1B and 1C describe the separation of compound 101 into its individual enantiomers, confirming the compound 101 is a mixture of two enantiomers SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

9 Latuda (lurasidone) SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

10 Latuda (lurasidone) SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

11 Latuda (lurasidone) Compound 101 is made from compounds 201 and 251; compound 201 is a racemic mixture and its use in the synthesis of compound 101 necessarily results in compound 101 also being a racemic mixture SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

12 Latuda (lurasidone) The 372 patent does not provide optical activity data for the HCl salt of compound 101, demonstrating that it is racemic By contrast, the 372 patent states that the HCl salt of the (+)-enantiomer of compound 101 has an optical rotation of Defs. cite to extrinsic evidence showing that illustration of a single enantiomer is shorthand for the racemic mixture SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

13 Latuda (lurasidone) Federal Circuit: the plain claim language and specification demonstrate that, at a minimum, claim 14 covers what it depicts: the ( )-enantiomer Appellants concede that the district court's judgment can be affirmed if we conclude that claim 14 at least covers the ( )-enantiomer... We therefore express no opinion on the remainder of the district court's construction. Of equal importance is the lack of anything in the claim language limiting its scope to a racemate or racemic mixture. 372 specification confirms that the ( )-enantiomer is included, describing it as a preferred embodiment. SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

14 Latuda (lurasidone) Claim 14 structure not shown, but Ex. 1(e) details the steps for obtaining Compound No. 105, the ( )-enantiomer, from Compound No. 101 Provides data on Compound No. 105's physical properties Intrinsic record supports including the ( )-enantiomer the specific enantiomer that is displayed in the claim and described as a preferred embodiment within claim 14's scope SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

15 Latuda (lurasidone) Fed. Cir. rejects argument that claim 14's scope should be coextensive with Compound 101 because of the similarities in the compounds' structures Specification is inconclusive regarding whether Compound 101 is a racemic mixture No use of racemate or racemic mixture '372 patent sheds no light on the relative ratio of each enantiomer present Specification does not define the claim 14 structure as Compound 101 Specification does not confine claim 14 to a racemic mixture That compound 101 is the only other place in the patent where the claim 14 compound appears is not enough to restrict claims Appellants organic chemistry textbooks are extrinsic evidence and of less weight SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

16 Latuda (lurasidone) Claim construction affirmed SUGHRUE MION PLLC Sumitomo Dainippon Pharma v. Emcure (Fed. Cir. April 16, 2018)

17 Case similarity to atorvastatin Ranbaxy argues that the structural formula of Claim 1 of the 893 patent represents only a genus of racemates Pfizer agreed that Claim 1 included racemates, but that it was not so limited; Claim 1 also represents R-trans enantiomers, S-trans enantiomers and unequal mixtures thereof The parties agreed that Claim 1 formula depicts an enantiomer, and agreed that such was not the meaning of the claimed structure SUGHRUE MION PLLC Pfizer v. Ranbaxy (Fed. Cir. August 2, 2006)

18 Case similarity to atorvastatin All 4 isomers of claim 1 are shown above R-trans, R-cis, S-trans, S-cis SUGHRUE MION PLLC Pfizer v. Ranbaxy (Fed. Cir. August 2, 2006)

19 Case similarity to atorvastatin Title, Abstract and Background sections of the '893 patent describe the invention as "trans" compounds Summary of the Invention describes "certain trans" compounds and the "broadest aspect of the present invention" as "compounds of structural formula I. Detailed Description section describes the "compounds of the present invention" as a "class of trans..." compounds. SUGHRUE MION PLLC Pfizer v. Ranbaxy (Fed. Cir. August 2, 2006)

20 Case similarity to atorvastatin The patent expressly states: Contemplates all trans-form compounds, including the individual R-trans isomer. No words of limitation or chemical symbols used in claim 1 to restrict the meaning of "trans" or "trans-form" to the trans-racemate SUGHRUE MION PLLC Pfizer v. Ranbaxy (Fed. Cir. August 2, 2006)

21 Case similarity to atorvastatin In contrast, dependent Claim 5 five used trans-(+/-) to designate a racemic mixture That the inventor knew how to limit a claim to a racemate, but chose not to so restrict the other claims of the patent A depiction of an enantiomer can sometimes include or specify a racemate, but Ranbaxy has not demonstrated that, to a POSA, such a depiction always or even usually specifies a racemate Improper to limit claimed invention to racemates simply because all reaction sequences and examples are racemic Claims are not limited to the 893 patent examples; improper to import those limitations into the claims SUGHRUE MION PLLC Pfizer v. Ranbaxy (Fed. Cir. August 2, 2006)

22 Case similarity to atorvastatin Table 1 examples are designated as representative examples Patent states these examples are illustrative and are not to be read as limiting the scope of the invention Representations to other patent offices in foreign counterpart applications do not limit Claim 1 to racemates only Arguments made in other, later filed, U.S. applications do not limit Claim 1 to racemates only Claim 1 of the '893 patent embraces all trans-form isomers, including enantiomeric atorvastatin calcium SUGHRUE MION PLLC Pfizer v. Ranbaxy (Fed. Cir. August 2, 2006)

23 Lyrica (pregabalin) What if the compound is written out? Claim 1 of Pfizer s 819 patent directed to pregabalin During claim construction, challengers argued Claim 2 covered only the racemic form (50/50 mixture of R and S) of isobutyl GABA, not single enantionmers or nonracemic mixtures Pfizer argued that narrow construction would ignore the plain specific language of the claim, which does not limit the form of the claimed compound SUGHRUE MION PLLC Pfizer v. Teva (Fed. Cir. Feb. 6, 2014)

24 Lyrica (pregabalin) Generics: Tables 1 and 2 contained test results pertaining only to the racemate, not other mixtures with differing enantiomeric compositions The limited association of the subject matter of Claim 2 with only 3- isobutyl GABA warrants narrower construction Fed. Cir: Absent clear disavowal or lexicographic definition, the reporting of test results limited to a racemate does not warrant importing racemic limitation into Claim 2 Patentee used the term (R/S) to specify tested compounds were racemic SUGHRUE MION PLLC Pfizer v. Teva (Fed. Cir. Feb. 6, 2014)

25 Lyrica (pregabalin) Fed. Cir: Patentees inclusion of test results of the compound s racemate juxtaposed with the lack of any racemic limitation in the claim language shows patentees intent not to limit the compound being claimed to its racemate Patentees knew how to specify racemic 3-isobutyl GABA from the compound generally, and did not do so in Claim 2 Prosecution history does not evince a disclaimer of non-racemic forms At trial, appellants expert conceded that Claim 2 covered 3-isobutyl GABA in any isomeric form Claim 2 not limited to racemic form SUGHRUE MION PLLC Pfizer v. Teva (Fed. Cir. Feb. 6, 2014)

26 Celexa (citalopram) Infosint s 973 patent directed to a method for manufacturing an intermediate 5-carboxyphthalide, used to produce citalopram Lundbeck manufactures 5-carboxyphthalide at 7 different global facilities, and uses it to produce citalopram Lundbeck argues citalopram should be construed as the racemic mixture, not including its S-enantiomer individually R&R construed citalopram to include the S-enantiomer, the R-enantiomer, the racemate, or any other mixture of the enantiomers Lundbeck objects, arguing that court failed to consider all relevant portions of the intrinsic evidence SUGHRUE MION LLP Infosint v. Lundbeck (S.D.N.Y. March 27, 2009)

27 Celexa (citalopram) R&R considered all intrinsic evidence, including the '431 and '724 applications incorporated by reference Both applications refer to "citalopram" by name, without reference to stereochemistry Claim 1 of WO 00/ SUGHRUE MION LLP Infosint v. Lundbeck (S.D.N.Y. March 27, 2009)

28 Celexa (citalopram) Claims 1 and 6 of Italian Pat. Appln. MI SUGHRUE MION LLP Infosint v. Lundbeck (S.D.N.Y. March 27, 2009)

29 Celexa (citalopram) Defendants expert stated: "[a]bsent definition of the threedimensional stereochemistry via a stereochemical indicator, the chemical name or structure includes the S-enantiomer, the R-enantiomer, the racemate, [or mixtures thereof]. Application leading to 973 patent described the invention as one that "allows the preparation of two enantiomers of citalopram." SUGHRUE MION LLP Infosint v. Lundbeck (S.D.N.Y. March 27, 2009)

30 Celexa (citalopram) Incorporated 431 application states that the invention described therein "relates to a novel method for the preparation of citalopram, its enantiomers and acid addition salts thereof. Intrinsic evidence demonstrates that the inventors used the term citalopram to refer to the compound in any of its forms: either enantiomer, mixtures thereof, or the racemate Lundbeck argues that the 973 specification statement that citalopram is a well-known antidepressant drug confirms the racemic only construction, since only Celexa was commercialized at the time of filing Court rejects Lundbeck argument, since 431 and 724 applications use the term in a broader sense SUGHRUE MION LLP Infosint v. Lundbeck (S.D.N.Y. March 27, 2009)

31 Naropin (The Form of the Active Ingredient) Naropin (ropivicane HCl monohydrate) (RHM) is used as an injectable local anesthetic for surgery and pain management Claim 1 of Abraxis 086 patent recites "(S)-(-)-1-propyl-2',6'- pipecoloxylidide hydrochloride, wherein the compound is in the form of its monohydrate" Q: is the claim limited to solid, crystalline form? Or does it include RHM in solution? SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

32 Naropin (The Form of the Active Ingredient) Plaintiffs: Words of Claim 1 do not specify any physical state Applicants never disclaimed or disavowed RHM in solution Other claims support that RHM not limited to a solid: Claim 4 refers to isolating the monohydrate after it is created in solution Claim 6 refers to administering solutions 086 patent specification refers to RHM being created in, or existing in, solution Pharmaceutical preparations in solution containing the new compound as an active ingredient SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

33 Naropin (The Form of the Active Ingredient) Defendants: Repeated statements in 086 patent about RHM being a solid, crystalline form Description as the monohydrate indicates a well-defined water content, and thus a solid Clearly defined melting point of RHM indicates a crystalline solid Extrinsic evidence showing that crystalline forms are solid, and lose long-range order that defines a crystal upon dissolution/dissociation SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

34 Naropin (The Form of the Active Ingredient) Court: Claim 1 encompasses RHM both as a solid and in solution Words of claim 1 do not specify any physical state Claims 4, 6 indicate RHM can be in solution by referring to "isolating the monohydrate" after it is created in solution In solution, RHM crystals lose the long range order associated with the crystalline solid but maintain the essential structural features and characteristics that make RHM a unique compound, including great stability, a high melting point, and water locked tightly into the structure SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

35 Naropin (The Form of the Active Ingredient) When RHM is introduced to an aqueous solution, the ropivacaine, chloride and water structures do not break up or disassociate and go their own way throughout the solution... Instead, water within the RHM structure stays in place locking two ropivacaine cations together. Also, due to electrostatic and hydrogen bonding, the chlorides would stay in place and hold the structure together. Accordingly, the essential structural units of RHM would hold up in solution. SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

36 Naropin (The Form of the Active Ingredient) PXRD obtained for product prepared by evaporation of water from Navinta s 0.2%, 0.5% and 1.0% samples Comparison to USP monograph PXRD data confirmed presence of RHM in each sample Water content of 5.5% consistent with monohydrate form SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

37 Naropin (The Form of the Active Ingredient) Navinta ANDA directed to RHM injection held to infringe Product claims directed to substantially optically pure enantiomer in monohydrate form Method claims for inducing local anesthesia Induced infringement based on product label SUGHRUE MION LLP Abraxis v. Navinta (D.N.J. August 3, 2009)

38 Nexium (The Salt of the Active Ingredient) Nexium - esomeprazole magnesium used to treat GERD, acid reflux AZ s 504 patent claims a formulation What constitutes the active ingredient for purposes of infringement? SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

39 Nexium (The Salt of the Active Ingredient) Hanmi Pharms. filed an ANDA based on esomeprazole strontium AZ alleged infringement of Claim 1, asserting that Sr was an alkaline salt covered by the claim Hanmi argued the claims were limited to the salts disclosed in the specification SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

40 Nexium (The Salt of the Active Ingredient) '504 Patent Abstract U.S. Patent No. 5,714,504 ('504 Patent) SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

41 Hanmi - an express definition '504 patent, col. 2, ll D.I. 86-2, '504 patent, col. 2, l. 50 col. 3, l. 15 SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

42 504 File History None of the claims as filed broadly included alkaline salts SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

43 Prosecution History Examiner Interview Summary Record of Jan 21, 1997 D.I. 111, '504 patent prosecution history, (HAN ) 43

44 'the genus disclosed and claimed herein' The scope of the genus claimed "herein" was the one that was disclosed D.I. 111, '504 patent prosecution history, 2/18/1997 Amendment (HAN ) 44

45 "the invention... mentioned above" D.I. 86-2, '504 patent, col. 2, ll D.I. 86-2, '504 patent, col. 5, ll

46 Nexium (The Salt of the Active Ingredient) AZ argued "exemplified by... " D.I. 86-2, '504 patent, col. 5, ll SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

47 Nexium (The Salt of the Active Ingredient) AZ argued claim differentiation Because Claim 3 recites the 6 salt species and depends from Claim 1, the alkaline salt of claim one is necessarily broader in scope than the six species SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

48 Nexium (The Salt of the Active Ingredient) SUGHRUE MION LLP Astrazeneca v. Hanmi (Fed. Cir. December 9, 2013)

49 Torisel (temsirolimus) Pfizer s Torisel - used for the treatment of advanced renal cell carcinoma Temsirolimus is a hydroxy ester derivative of sirolimus ( also known as rapamycin) Pfizer s 718 patent is directed to rapamycin hydroxyesters claim 15 is: SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

50 Torisel (temsirolimus) Parties dispute the meaning of rapamycin Plaintiffs proposed construction Rapamycin means rapamycin, i.e., a compound with a known structure, as depicted, for example, in the figure in U.S. Patent No. 4,650,803, and as further depicted in the 718 patent, wherein R1 and R2 are both hydrogen Defendants proposed construction "compounds containing a macrocyclic triene ring structure produced by Streptomyces hygroscopicus, having antibiotic effects. SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

51 Defendants: rapamycin" expressly defined '718 patent, Col. 1, lines SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

52 Def s: other rapamycins confirm no single structure 718 patent, Col. 4, lines 38-50

53 Plaintiff s proposed construction Prior art 803 Patent 718 Patent-in-suit SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

54 '718 patent never defines rapamycin * * *

55 803 patent rapamycin isomers SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

56 803 patent rapamycin isomers SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

57 Torisel (temsirolimus) SUGHRUE MION LLP Pfizer v. Accord (D. Del. May 6, 2013)

58 Summary The active ingredient will be construed to be what the intrinsic evidence dictates, even if seemingly nonsensical Chemical names and structures without stereochemical indicators will usually be considered to include enantiomers and mixtures thereof, unless intrinsic evidence clearly dictates otherwise Chemical structures with stereochemical indicators can sometimes include racemic and enantiomeric mixtures alkaline salt, pharmaceutically acceptable salt, will generally be construed broadly, unless intrinsic evidence clearly dictates otherwise Terms like crystalline [compound] monohydrate "do not necessarily mean solid form SUGHRUE MION LLP

59 Summary When drafting applications and claims, include accurate structures, names, and stereochemical depictions of isomers when appropriate State what is intended to be included (e.g., the compounds of the present invention include all stereoisomers, enantiomers, and mixtures thereof ) For racemic mixtures, preferably use solid bonds (not wedges or dashed lines) and describe it as a racemic mixture For enantiomers, include stereochemical depictions When claiming enantiomers that are optically pure, or substantially free of the opposite enantiomer, provide purity ranges in the specification that are broad, more preferred, and most preferred SUGHRUE MION LLP

60 Summary Include a specific claim to, e.g., the (-) enantiomer of the desired compound Include a claim reciting structure and a property, e.g., optical rotation, melting point Don t rely on prior art or external references to define key elements of claims SUGHRUE MION LLP

61 !फर %मल(ग. Thank you.