obviousness in view of ksr tc1600-specific examples jean witz tqas, tc1600

Obviousness in View of KSRObviousness in View of KSRTC1600-Specific ExamplesTC1600-Specific Examples

Jean WitzJean WitztQAS, TC1600tQAS, TC1600

22

Post-KSR CasesPost-KSR Cases

U.S. Court of Appeals for the Federal Circuit

U.S. District Court for the Southern District of New York

Board of Patent Appeals and Interferences

33

U.S. Court of Appeals for the Federal Circuit

Takeda Chemical Industries v. Alphapharm Pty, Ltd., 492 F.3d 1350, 83 USPQ2d 1169 (Fed. Cir. 2007)

Pharmastem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342, 83 USPQ2d 1289 (Fed. Cir. 2007)

44

U.S. District Court for the Southern District of New York

In re Omeprazole Patent Litigation, 490 F. Supp. 2d 381 (S.D. N.Y. June 1, 2007)

McNeil-PPC, Inc. v Perrigo Company, [cite] (S.D. N.Y. June 5, 2007)

55

Board of Patent Appeals and Interferences

Ex parte Kubin, 83 USPQ2d Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 1410 (Bd. Pat. App. & Int. 2007)2007)

66

Takeda v. Alphapharm

Defendant filed ANDA to Defendant filed ANDA to market generic version of market generic version of pioglitazone (ACTOSpioglitazone (ACTOS®®) – ) – diabetes 2 treatmentdiabetes 2 treatment

Plaintiff owns patent to Plaintiff owns patent to pioglitazone and sued for pioglitazone and sued for infringement in District Court infringement in District Court (S.D. N.Y.)(S.D. N.Y.)

77


Defendant asserted invalidity Defendant asserted invalidity based on obviousnessbased on obviousness

District Court concluded District Court concluded patent validpatent valid

Defendant appealed to the Defendant appealed to the Federal CircuitFederal Circuit

88


ClaimClaim Pioglitazone – a thiazolidinedione Pioglitazone – a thiazolidinedione

(TZD) with an ethyl-substituted (TZD) with an ethyl-substituted pyridyl ring at the 5-positionpyridyl ring at the 5-position

Prior ArtPrior Art Reference teaching “compound Reference teaching “compound

b”, which differs from b”, which differs from pioglitazone by having a methyl in pioglitazone by having a methyl in place of ethyl in the 6-position, place of ethyl in the 6-position, instead of the 5-positioninstead of the 5-position

99


Defendants’ Theory of Defendants’ Theory of ObviousnessObviousness ““Compound b” was known to be an Compound b” was known to be an

effective anti-diabetic compound effective anti-diabetic compound Homologation and ring-walking Homologation and ring-walking

were within the skill of one of were within the skill of one of ordinary skill in the artordinary skill in the art

It would have been obvious to It would have been obvious to modify “compound b” via modify “compound b” via homologation and ring-walking in homologation and ring-walking in order to produce another compound order to produce another compound with anti-diabetic activitywith anti-diabetic activity

1010


Plaintiffs’ RebuttalPlaintiffs’ Rebuttal No reason to choose“compound b” No reason to choose“compound b”

out of “hundreds of millions of TZD out of “hundreds of millions of TZD compounds” in the prior art compounds” in the prior art disclosuredisclosure

Review article of 101 TZD compounds Review article of 101 TZD compounds (including “compound b”) teaches (including “compound b”) teaches away from “compound b”away from “compound b”

Unexpected reduced toxicity of Unexpected reduced toxicity of pioglitazone compared to “compound pioglitazone compared to “compound b”b”

1111


Court RationaleCourt Rationale No “finite number of No “finite number of

identifiable, predictable identifiable, predictable solutions” solutions”

Prior art provided “broad Prior art provided “broad selection of compounds”selection of compounds”

Closest prior art compound Closest prior art compound exhibited negative propertiesexhibited negative properties

HoldingHolding Patent valid – compound nonobviousPatent valid – compound nonobvious

1212

Pharmastem v. Viacell

Plaintiff owned patents to Plaintiff owned patents to cryopreserved umbilical cord cryopreserved umbilical cord bloodblood

Defendants provided service of Defendants provided service of cryopreservation of umbilical cryopreservation of umbilical cord bloodcord blood

Plaintiff alleged infringementPlaintiff alleged infringement

Defendants asserted invalidity Defendants asserted invalidity

1313


ClaimsClaims A cryopreserved therapeutic A cryopreserved therapeutic

composition comprising umbilical composition comprising umbilical cord blood hematopoietic stem cellscord blood hematopoietic stem cells

A method for hematopoietic or A method for hematopoietic or immune reconstitution comprising immune reconstitution comprising cryopreserving of umibilical cord cryopreserving of umibilical cord blood hematopoietic stem cells, blood hematopoietic stem cells, thawing, and administering to a thawing, and administering to a humanhuman

1414


Prior ArtPrior Art Knudtzon referenceKnudtzon reference Ende referenceEnde reference Prindull referencePrindull reference Koike referenceKoike reference Vidal referenceVidal reference

All prior art references discuss the All prior art references discuss the presence of stem cells in cord bloodpresence of stem cells in cord blood

1515


Defendants’ Theory of Defendants’ Theory of ObviousnessObviousness Prior art identified the presence of Prior art identified the presence of

stem cells in umbilical cord blood stem cells in umbilical cord blood (Admissions in spec, Prindull)(Admissions in spec, Prindull)

Prior art taught that stem cells in Prior art taught that stem cells in umbilical cord blood could be umbilical cord blood could be cryopreserved and thawed (Koike, cryopreserved and thawed (Koike, Vidal)Vidal)

Prior art suggested the use of stem Prior art suggested the use of stem cells for transplantation (Vidal, Ende, cells for transplantation (Vidal, Ende, Knudtzon)Knudtzon)

1616


Plaintiffs’ RebuttalPlaintiffs’ Rebuttal Prior art used “flawed Prior art used “flawed

nomenclature”nomenclature” No reasonable expectation of No reasonable expectation of

success based on prior success based on prior transplants of analogous stem transplants of analogous stem cells (blood, marrow)cells (blood, marrow)

Long-felt needLong-felt need Commercial successCommercial success

1717


Court’s rationaleCourt’s rationale Could not reconcile expert testimony Could not reconcile expert testimony

with statements in the specificationwith statements in the specification Did not agree with expert that Did not agree with expert that

terminology was “flawed”terminology was “flawed” Prior art references to “stem cells” Prior art references to “stem cells”

were consistent with Applicants’ were consistent with Applicants’ statements in the specificationstatements in the specification

Citing KSR, determined that Citing KSR, determined that invention was confirmation of what invention was confirmation of what was already believed to be truewas already believed to be true

1818


HoldingHolding Patent invalid – method and composition Patent invalid – method and composition

obviousobvious

Dissent – Judge NewmanDissent – Judge Newman Majority engaged in impermissible Majority engaged in impermissible

hindsighthindsight Ignored peer responseIgnored peer response Ignored jury verdictIgnored jury verdict Ignored scientific expertsIgnored scientific experts Ignored agency expertiseIgnored agency expertise

1919

Highlights and Highlights and GuidanceGuidance

Evidence is critical to the Evidence is critical to the determination of obviousnessdetermination of obviousness Court in Takeda focused on Court in Takeda focused on

“teaching away” and “teaching away” and unexpected resultsunexpected results

Court in Pharmastem focused on Court in Pharmastem focused on Applicants’ statements in Applicants’ statements in specificationspecification

2020

In re Omeprazole

Plaintiff Astrazeneca filed Plaintiff Astrazeneca filed multiple infringement suits multiple infringement suits against several generic against several generic manufacturers based on ANDAs manufacturers based on ANDAs for omeprazole (Prilosecfor omeprazole (Prilosec®®))

Defendants asserted invalidity Defendants asserted invalidity on multiple theories including on multiple theories including obviousnessobviousness

2121

In re Omeprazole

ClaimClaim A formulation comprisingA formulation comprising (a) a core comprising omeprazole (a) a core comprising omeprazole

plus an alkaline reacting compound plus an alkaline reacting compound (ARC);(ARC);

(b) an inert subcoating, which is (b) an inert subcoating, which is soluble or rapidly disintegrates in soluble or rapidly disintegrates in water, disposed on the core region, water, disposed on the core region,

(c) an outer layer disposed on the (c) an outer layer disposed on the subcoating comprising an enteric subcoating comprising an enteric coatingcoating

2222

In re Omeprazole

Prior ArtPrior Art References disclosed a core with References disclosed a core with

a subcoating and enteric coating a subcoating and enteric coating but did not disclose omeprazolebut did not disclose omeprazole

References disclosed References disclosed omeprazole but did not disclose omeprazole but did not disclose a subcoating or an alkaline a subcoating or an alkaline reacting compound reacting compound

References described References described subcoatings and techniques but subcoatings and techniques but did not disclose omeprazoledid not disclose omeprazole

2323

In re Omeprazole

Defendants’ Theory of Defendants’ Theory of ObviousnessObviousness Prior art disclosed that acid labile Prior art disclosed that acid labile

pharmaceuticals are pharmaceuticals are conventionally subcoated and conventionally subcoated and coatedcoated

Prior art disclosed that it Prior art disclosed that it conventional to use subcoatingsconventional to use subcoatings

Prior art disclosed that it was Prior art disclosed that it was conventional to use an ARCconventional to use an ARC

2424

In re Omeprazole

Court’s RationaleCourt’s Rationale Prior art compounds that were Prior art compounds that were

subcoated and coated were not subcoated and coated were not comparable to omeprazolecomparable to omeprazole

Prior art compounds that were Prior art compounds that were subcoated and coated were subcoated and coated were delivered to different part of the delivered to different part of the GI tractGI tract

Prior art disclosure to omeprazole Prior art disclosure to omeprazole formulations did not disclose formulations did not disclose stability problemsstability problems

2525

In re Omeprazole

Court’s Rationale, continuedCourt’s Rationale, continued References taught away from References taught away from

subcoated formulationsubcoated formulation Expert testimony of “multitude of Expert testimony of “multitude of

possible paths and dead-ends” in possible paths and dead-ends” in formulation attemptsformulation attempts

HoldingHolding Patent valid – formulation Patent valid – formulation

unobviousunobvious

2626

McNeil-PPC v Perrigo

Plaintiffs filed infringement Plaintiffs filed infringement suit based on ANDAs filed by suit based on ANDAs filed by Defendants on combination of Defendants on combination of famotidine and antacids famotidine and antacids (Pepcid(Pepcid®® Complete) Complete)

Defendants assert invalidity Defendants assert invalidity based on the theory of based on the theory of obviousnessobviousness

2727


ClaimClaim Solid oral dosage form Solid oral dosage form

comprisingcomprising

(a) coated famotidine granules(a) coated famotidine granules

(b) Al(OH)(b) Al(OH)33 or Mg(OH) or Mg(OH)22 granules granules

Wherein the coating on the Wherein the coating on the famotidine is impermeable to famotidine is impermeable to the Al(OH)the Al(OH)33 or Mg(OH) or Mg(OH)22

2828


Prior ArtPrior Art Reference disclosed Reference disclosed

combination of uncoated combination of uncoated histamine Hhistamine H22 receptor receptor antagonists and antacidsantagonists and antacids

References disclosed coating References disclosed coating granulated medicaments to granulated medicaments to mask taste of active ingredientmask taste of active ingredient

Reference acknowledged the Reference acknowledged the bitter taste of cimetidinebitter taste of cimetidine

2929


Defendants’ Theory of Defendants’ Theory of ObviousnessObviousness All relevant limitations of the All relevant limitations of the

claim appeared in the prior artclaim appeared in the prior art One of ordinary skill in the art One of ordinary skill in the art

would have coated the famotidine would have coated the famotidine in the prior art combination in the prior art combination formulation to mask the bitter formulation to mask the bitter taste of famotidinetaste of famotidine

3030


Plaintiffs’ RebuttalPlaintiffs’ Rebuttal There was no suggestion that the There was no suggestion that the

combinationcombination formulation in the formulation in the prior art was bitter, therefore prior art was bitter, therefore there was no reason to coat the there was no reason to coat the famotidine alonefamotidine alone

Other modes of taste-masking Other modes of taste-masking were preferable due to cost of were preferable due to cost of coated granulescoated granules

3131


Court’s RationaleCourt’s Rationale The combination of coated The combination of coated

famotidine and the antacids famotidine and the antacids provided no more than predictable provided no more than predictable results, citing KSRresults, citing KSR

Costs alone are not indicative of Costs alone are not indicative of non-obviousnessnon-obviousness

HoldingHolding Patent invalid – formulation obviousPatent invalid – formulation obvious

3232


Recognition of problems in the Recognition of problems in the prior art as well as answers to prior art as well as answers to problems in the prior art may problems in the prior art may lead to a finding of obviousnesslead to a finding of obviousness In McNeil, single problem is solved In McNeil, single problem is solved

with predictable resultswith predictable results In Omeprazole, numerous In Omeprazole, numerous

variables suggested that the variables suggested that the results would not be predictableresults would not be predictable

3333

Ex parte KubinEx parte Kubin

ClaimClaim An isolated nucleic acid molecule An isolated nucleic acid molecule

comprising a polynucleotide comprising a polynucleotide encoding a polypeptide at least encoding a polypeptide at least 80% identical to amino acids 22 – 80% identical to amino acids 22 – 221 of SEQ ID NO:2, wherein the 221 of SEQ ID NO:2, wherein the polypeptide binds CD48polypeptide binds CD48

3434


Prior ArtPrior Art Reference disclosed p38 protein Reference disclosed p38 protein

(same protein as NAIL) and (same protein as NAIL) and methods of isolation by using mAbs methods of isolation by using mAbs as well as methods of obtaining the as well as methods of obtaining the polynucleotide sequence but does polynucleotide sequence but does not disclose the sequence of p38not disclose the sequence of p38

Reference disclosed the nucleic acid Reference disclosed the nucleic acid sequence of the highly conserved sequence of the highly conserved murine version of p38 and identified murine version of p38 and identified a human homologuea human homologue

3535


Examiner’s ArgumentsExaminer’s Arguments One of ordinary skill in the art One of ordinary skill in the art

would have been motivated to would have been motivated to apply conventional methodologies apply conventional methodologies to isolate and identify the cDNA to isolate and identify the cDNA sequence of human NAIL in view of sequence of human NAIL in view of the teachings of the prior artthe teachings of the prior art

3636


Appellants’ ArgumentsAppellants’ Arguments Cited references did not provide Cited references did not provide

adequate written description of adequate written description of cDNA of NAILcDNA of NAIL

Reliance on In re Deuel – Reliance on In re Deuel – knowledge of a protein does not knowledge of a protein does not render obvious the cDNA encoding render obvious the cDNA encoding itit

No motivation to combine the No motivation to combine the referencesreferences

3737


Board’s RationaleBoard’s Rationale State of the art has advancedState of the art has advanced Reliance on KSR – “obvious to try” Reliance on KSR – “obvious to try”

in view of limited methodologies in view of limited methodologies available to isolate NAIL cDNAavailable to isolate NAIL cDNA

Methodologies had reasonable Methodologies had reasonable expectation of successexpectation of success

3838


Advancements in the state of Advancements in the state of the art may render that which the art may render that which was once unpredictable to was once unpredictable to become predictablebecome predictable

3939

Thank You!Thank You!

[email protected]@uspto.gov

571-272-0927571-272-0927

obviousness in view of ksr tc1600-specific examples jean witz tqas, tc1600

Documents

n n pharmastem therapeutics

n n mcneilppc

postksr cases n n

obviousness n district

treatment n plaintiff

alphapharm n court rationale

negative properties

patent valid n defendant