UNITED S'TATES PATIEN'T AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Addrcss: COMMISSIONER FOR PATENTS
`PO Box 1450
`Alexandria, Virginia 22313-1450
`www uspto gov
`
`APPLICATION NO.
`
`FILING DATE
`
`13/340,522
`
`12/29/2011
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`Joseph J. Buggy
`
`25922-819.301
`
`7251
`
`7590
`03/13/2013
`21971
`WILSON, SONSINI, GOODRICII & ROSATI
`650 PAGE MILL ROAD
`PALO AITO, CA 94304-1050
`
`EXAMINER
`
`RAMACHANDRAN, IJMAMAHESWART
`
`ART UNIT
`
`PAPER NTMI3ER
`
`1627
`
`MAIL DATE
`
`DELIVERY MODE
`
`03/13/2013
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`PTO,-90A (Rev. 04/07)
`
`Exhibit 2008 Page 001
`
`Pharmacyclics LLC - Ex. 2008
`Coalition for Affordable Drugs IV LLC v. Pharmacyclics LLC
`Case IPR2015-01076
`
`

`

`Office Action Summary
`
`Application No.
`
`13/340,522
`
`Examiner
`
`Applicant(s)
`
`BUGGY ET AL.
`
`Art Unit
`
`UMAMAHESWARI
`RAMACHANDRAN
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
`In no event, however, may a reply be timely filed
`Extensions of time may be available under the provisions of 37 CFR 1.136(a)
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`(35 U.S.C. § 133).
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`Status
`
`1627
`
`4)-
`
`1)® Responsive to communication(s) filed on 04 February2013.
`2b)® This action is non-final.
`This action is FINAL.
`2a)-
`3)O An election was made by the applicant in response to a restriction requirement set forth during the interview on
`; the restriction requirement and election have been incorporated into this action.
`Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`Disposition of Claims
`5)® Claim(s) 131,132 and 134-149 is/are pending in the application.
`is/are withdrawn from consideration.
`5a) Of the above claim(s) __
`is/are allowed.
`Claim(s)
`6)-
`7)® Claim(s) 131, 132 and 134-149 is/are rejected.
`is/are objected to.
`8)O Claim(s)
`are subject to restriction and/or election requirement.
`Claim(s)
`9)-
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway
`program at a participating intellectual property office for the corresponding application. For more information, please see
`or send an inquiry to PPHfeedb~ck_@usoto..gv.
`htt://www.usto.g. o/patentsini eventsi pfi.rde .s
`Application Papers
`The specification is objected to by the Examiner.
`10)'
`is/are: a)O accepted or b)O objected to by the Examiner.
`11)" The drawing(s) filed on
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
`Priority under 35 U.S.C. § 119
`12)" Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)l All b)O Some * c)O None of:
`1.0 Certified copies of the priority documents have been received.
`2.0 Certified copies of the priority documents have been received in Application No.
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`* See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`1) ® Notice of References Cited (PTO-892)
`
`2) [
`
`Information Disclosure Statement(s) (PTO/SB!08)
`Paper No(s)/Mail Date 1/23/2013, 2/22/2013.
`
`3) [
`
`Interview Summary (PTO-413)
`Paper No(s)/Mail Date.
`4) Q Other:
`
`Exhibit 2008 Page 002
`
`

`

`U S Patent and Trademark Office
`PTOL-326 (Rev. 09-12)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20130307
`
`Exhibit 2008 Page 003
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 2
`
`DETAILED ACTION
`
`The office acknowledges Applicants' response to the Restriction Election dated
`
`1/3/2013. Applicants' have elected Group II with traverse. Applicants' argue that
`
`a relapsed or refractory non-Hodgkin's lymphoma is a species of relapsed or refractory
`
`hematological malignancy, the claims Group III overlap and are encompassed by the
`
`genus relapsed or refractory hematological malignancy. Also, Applicants have amended
`
`claim 132 to depend from claim 131. Accordingly, claims 131,132, and 134-149 as
`
`presented herein read on elected Group II. Applicants' arguments and amendment of
`
`claims have been considered and found to be persuasive. Applicants have cancelled
`
`claims 1-130, 133. Claims 131, 132, 134-149 are directed to a method of relapsed or
`
`refractory hematological malignancy in an individual comprising administering to the
`
`individual an inhibitor of Bruton's tyrosine kinase (Btk). Hence Group II and Group III
`
`claims (131, 132, 134-149) will be examined. Applicants have elected the species of
`
`lymphoma - mantle cell lymphoma (MCL), species of second cancer agent - rituximab
`
`(174722-31-7) and the following species for Btk inhibitor.
`
`RN 936563-96-1 HCAPLUS
`CN 2-Propen-l-one, 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1 H-pyrazolo[3,4-
`d]pyrimidin-l-yl]-l-piperidinyl]- (CA INDEX NAME)
`
`Exhibit 2008 Page 004
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 3
`
`(stereoisomer - ibrutinib - PCI-32765 (936563-96-1), (specification p 82, [00262,
`
`compound 1], in US publication, p 34, compound 1). The claims will be examined to the
`
`extent they read on the elected species.
`
`The restriction requirement election is made Final.
`
`Note: The claim set dated 3/26/2012 that was examined for Restriction Election
`
`Requirement had claim 150. However the claim set dated 2/4/2013 (examined for this
`
`office action) do not have claim 150 and there is no cancelled claim 150.
`
`The claims corresponding to the elected subject matter are 131, 132, 134-149
`
`are herein acted on the merits.
`
`Application Priority
`
`This application filed 12/29/2011 is a continuation of 13153317, filed 06/03/2011,
`
`Claims Priority from Provisional Application 61351130, filed 06/03/2010, Claims Priority
`
`from Provisional Application 61351655, filed 06/04/2010, Claims Priority from
`
`Provisional Application 61351793, filed 06/04/2010, Claims Priority from Provisional
`
`Application 61351762, filed 06/04/2010, Claims Priority from Provisional Application
`
`61419764, filed 12/03/2010, Claims Priority from Provisional Application. 61472138, filed
`
`04/05/2011.
`
`Information Disclosure Statement
`
`The information disclosure statements (IDS) filed on 1/23/2013, 2/22/2013 are in
`
`compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being
`
`considered by the Examiner. The foreign references and non-patent literature
`
`Exhibit 2008 Page 005
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 4
`
`documents have been submitted for application 13/153,317 (IDS dated 8/5/11,
`
`2/15/2013).
`
`Compliance with Sequence Rules
`
`This application contains sequence disclosures that are encompassed by the
`
`definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. §1.821 (a)
`
`(1) and (a) (2). However, this application fails to fully comply with the requirements of 37
`
`C.F.R. 1.821 through 1.825; Applicants' attention is directed to the final rulemaking
`
`notice published at 55 FR 18230 (May 1, 1990), and 1114 ©G 29 (May 15, 1990).
`
`The polypeptide of AVLESEEELYSSARQ, paragraph [0148] is recited without
`
`appropriate SEQ ID NO.
`
`If the noted sequences are in the sequence listing as filed, Applicants must
`
`amend the specification to identify the sequences appropriately by SEQ ID NO. If the
`
`noted sequences are not in the sequence listing as filed, Applicants must provide (1) a
`
`substitute copy of the sequence listing in both computer readable form (CRF) and paper
`
`copy, (2) an amendment directing its entry into the specification, (3) a statement that the
`
`content of the paper and CRF copies are the same and, where applicable, include no
`
`new matter as required by 37 C.F.R. 1.821 (e) or 1.821 (f) or 1.821 (g) or 1.821 (b) or
`
`1.825(d), and (4) any amendment to the specification to identify the sequences
`
`appropriately by SEQ ID NO.
`
`Exhibit 2008 Page 006
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 5
`
`Claim Rejections - 35 USC § 112
`
`The following is a quotation of 35 U.S.C. 112(a):
`(a) IN GENERAL.-The specification shall contain a written description of the invention,
`and of the manner and process of making and using it, in such full, clear, concise, and
`exact terms as to enable any person skilled in the art to which it pertains, or with which
`it is most nearly connected, to make and use the same, and shall set forth the best
`mode contemplated by the inventor or joint inventor of carrying out the invention.
`
`The following is a quotation of 35 U.S.C. 112 (pre-AIA), first paragraph:
`The specification shall contain a written description of the invention, and of the
`
`manner and process of making and using it, in such full, clear, concise, and exact terms
`
`as to enable any person skilled in the art to which it pertains, or with which it is most
`
`nearly connected, to make and use the same and shall set forth the best mode
`
`contemplated by the inventor of carrying out his invention.
`
`Claims 131, 132, 134-144, 146 are rejected under 35 U.S.C. 112, first paragraph,
`
`scope of enablement, because the specification, while being enabling for compounds of
`
`formula (D) administering a Btk inhibitor having the structure of Formula (D), does not
`
`reasonably provide enablement for overly broad genus method of administering
`
`unlimited possible genus of any Btk inhibitor (e.g., small molecule, peptide and/or any
`
`derivative thereof) that is defined only by functional reduction which includes, but not
`
`limited to, inhibiting Btk in any degree, by binding anywhere, and/or any related
`
`metabolic pathway enzyme(s) other than Btk itself, for example or treating by
`
`administering a generic Btk inhibitor compound which has specific bonding properties
`
`and forms a covalent bond with a cysteine residue of a Bruton's tyrosine kinase (Btk)
`
`The specification does not enable any person skilled in the art to which it pertains, or
`
`Exhibit 2008 Page 007
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 6
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`with which it is most nearly connected, to make the invention commensurate in scope
`
`with these claims.
`
`The test of enablement is whether one skilled in the art could make and use the
`
`claimed invention from the disclosures in the application coupled with information known
`
`in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d
`
`1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a
`
`single factor, but rather a conclusion reached by weighing many factors (See Ex parte
`
`Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400
`
`(Fed. Cir. 1988). The factors to be considered in determining whether undue
`
`experimentation is required are summarized In re Wands 858 F.2d 731,8 USPQ2nd
`
`1400 (Fed. Cir, 1988). The Court in Wands states: "Enablement is not precluded by the
`
`necessity for some experimentation such as routine screening. However,
`
`experimentation needed to practice the invention must not be undue experimentation.
`
`The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly,
`
`enablement of a claimed invention cannot be predicated on the basis of quantity of
`
`experimentation required to make or use the invention. "Whether undue
`
`experimentation is needed is not a single, simple factual determination, but rather is a
`
`conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d
`
`1404). The factors to be considered in determining whether undue experimentation is
`
`required include: (1) the quantity of experimentation necessary, (2) the amount or
`
`direction or guidance presented, (3) the presence or absence of working examples, (4)
`
`the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in
`
`Exhibit 2008 Page 008
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 7
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`the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the
`
`claims.
`
`(1) The nature of the invention and (2) Breadth of the claims: The invention is
`
`directed to a method of treating a relapsed or refractory hematological malignancy in an
`
`individual comprising administering to the individual an inhibitor of Bruton's tyrosine
`
`kinase (Btk). The claims are very broad with respect to the number of the Btk inhibitor
`
`compounds and its concentrations claimed in the method of treatment. Also the claims
`
`are broad with respect to relapsed or refractory hematological malignancy.
`
`Hematological malignancy includes B-cell malignancy, leukemia, lymphoproliferative
`
`disorder, or myeloid, a chronic lymphocytic leukemia (CLL), small lymphocytic
`
`lymphoma (SLL), high risk CLL, or a non-CLL/SLL lymphoma. In some embodiments,
`
`the hematological malignancy is follicular lymphoma, diffuse large B-cell lymphoma
`
`(DLBCL), mantle cell lymphoma, Waldenstrom's macroglobulinemia, multiple myeloma,
`
`marginal zone lymphoma, Burkitt's lymphoma, non-Burkitt high grade B cell lymphoma,
`
`or extranodal marginal zone B cell lymphoma. In some embodiments, the hematological
`
`malignancy is chronic myelogenous (or myeloid) leukemia, or acute lymphoblastic
`
`leukemia, relapsed or refractory diffuse large B-cell lymphoma (DLBCL), relapsed or
`
`refractory mantle cell lymphoma, relapsed or refractory follicular lymphoma, relapsed or
`
`refractory CLL; relapsed or refractory SLL; relapsed or refractory multiple myeloma.
`
`3) Amount of guidance provided by Applicant. The Applicant has described
`
`various compounds of Formula (D) and administering a Btk inhibitor for non-hodgkin's
`
`lymphoma, efficacy of a Btk inhibitor in patients with CLL or SLL (example 10), assay of
`
`Exhibit 2008 Page 009
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`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 8
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`drug combination in DoHH2 cells (example 17), However, there is no working example
`
`of treating a relapsed or refractory hematological malignancy with a generic Btk inhibitor
`
`compound or a Btk inhibitor compound which has specific bonding properties and forms
`
`a covalent bond with a cysteine residue of a Bruton's tyrosine kinase (Btk). These
`
`cannot be simply willed into existence. As was stated in Morton International Inc. v.
`
`Cardinal Chemical Co., 28 USPQ2d 1190, "The specification purports to teach, with
`
`over fifty examples, the preparation of the claimed compounds with the required
`
`connectivity. However...there is no evidence that such compounds exist...the examples
`
`of the '881 patent do not produce the postulated compounds...there is...no evidence that
`
`such compounds even exist." The same circumstance appears to be true here. Hence,
`
`applicants must show that any and all generic compounds which have specific bonding
`
`properties and form a covalent bond with a cysteine residue of a Bruton's tyrosine
`
`kinase (Btk) can be used to treat a relapsed or refractory hematological malignancy, or
`
`limit the claims accordingly.
`
`4) Unpredictability in the art. It is well established that "the scope of enablement
`
`varies inversely with the degree of unpredictability of the factors involved" and
`
`physiological activity is generally considered to be an unpredictable factor. (USPQ 18,
`
`24 (CCPA 1970). See In re Fisher, 427 F.2d 833,839, 166. In terms of the law, MPEP
`
`2107.03 states "evidence of pharmacological or other biological activity of a compound
`
`will be relevant to an asserted therapeutic use if there is a reasonable correlation
`
`between the activity in question and the asserted utility. Cross v. lizuka, 753 F.2d 1040,
`
`224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA
`
`Exhibit 2008 Page 010
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 9
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`1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980)." If correlation is
`
`lacking, it cannot be relied upon, Exparte Powers, 220 USPQ 924; Rey-Bellet and
`
`Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ
`
`688. Indeed, the correlation must have been established "at the time the tests were
`
`performed", Hoffman v. Klaus, 9 USPQ2d 1657.
`
`5) Number of working examples. Applicants have provided a design to study the
`
`effects of Btk inhibitor in R/R MCL (mantle cell lymphoma) (example 13, specification).
`
`Applicants have provided guidance towards administration of Btk inhibitors (alone) or in
`
`combination with other cancer agents in DOHH2 cells (examples 17 and 18).
`
`Applicants in general state administration of Btk inhibitors in the examples (including
`
`design study or prophetic examples) but do not explicitly state which compound was
`
`administered. Applicant has provided no working examples by administering a
`
`compound which has specific bonding properties and forms a covalent bond with a
`
`cysteine residue of a Bruton's tyrosine kinase (Btk).
`
`Within the specification, "specific operative embodiments or examples of the
`
`invention must be set forth. Examples and description should be of sufficient scope as
`
`to justify the scope of the claims. Markush claims must be provided with support in the
`
`disclosure for each member of the Markush group. Where the constitution and formula
`
`of a chemical compound is stated only as a probability or speculation, the disclosure is
`
`not sufficient to support claims identifying the compound by such composition or
`
`formula." See MPEP 608.01(p).
`
`Exhibit 2008 Page 011
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 10
`
`Applicants recite several claims (131, 139-144) towards a method of treating a
`
`relapsed or refractory hematological malignancy, however, no specific compound is
`
`defined. All that is recited is a statement that the compound has specific bonding
`
`properties and forms a covalent bond with a cysteine residue of a Bruton's tyrosine
`
`kinase (Btk). An applicant must clearly identify these things.
`
`Applicants certainly cannot "reach through" and claim a method of treating a
`
`disease by administering a Btk inhibitor compound which forms a covalent bond with a
`
`cysteine residue of a Bruton's tyrosine kinase (Btk) when compounds such as these
`
`may not be discovered for another 1,5, or 10 years. The Specification is not
`
`commensurate in scope with the notion that "any" compound that inhibits Btk which
`
`forms a covalent bond with a cysteine residue of a Bruton's tyrosine kinase (Btk)
`
`homolog would be effective in treating a relapsed or refractory hematological
`
`malignancy. The applicants have not provided any chemical or biological data and/or
`
`testing results of any compounds which "form a covalent bond with a cysteine residue of
`
`a Bruton's tyrosine kinase (Btk) other than previously mentioned.
`
`6) Level of skill in the art. The artisan using Applicants invention would be a
`
`doctor with a M.D. degree, and having several years of professional experience.
`
`(7) The Quantity of experimentation:
`
`The breadth of the claims is overly broad. It is towards a method of administering
`
`unlimited possible genus of any Btk inhibitor (e.g., small molecule, peptide and/or any
`
`derivative thereof) that is defined only by functional reduction which includes, but not
`
`limited to, inhibiting Btk in any degree, by binding anywhere, and/or any related
`
`Exhibit 2008 Page 012
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 11
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`metabolic pathway enzyme(s) other than Btk itself, even if said genus Btk inhibitor is
`
`required to makes covalent bond to C481 towards treating hematological malignancy.
`
`As described above hematological malignancy is a genus of diseases. However, the
`
`prior art and the instant disclosure does not teach sufficient direction or guidance on
`
`how to make any Btk inhibitor or any small organic molecule, peptide and/or variants
`
`thereof which inhibits any Btk as encompassed by breadth noted above. Although, the
`
`specification discloses species working examples of Btk inhibitor making covalent bond
`
`with C481, the making and using any Btk inhibitor with/without making covalent bind
`
`with C481 and/or with/without inhibiting Btk itself is unpredictable while maintaining said
`
`function of inhibiting Btk without sufficient guidance and direction. Thus, it would be
`
`unpredictable for one skilled in the art to create any unlimited Btk inhibitor as
`
`encompassed by the instant claims and administer said genus Btk inhibitor noted in
`
`breadth of claims above; and would requires undue experimentation to retain Btk
`
`inhibition when administer into any animal, for example. It is not predictable from the art
`
`or from the specification of how every hematological malignancy can be treated by all
`
`the Btk compounds claimed. For all of the above reasons, it would require undue
`
`experimentation necessary to practice the full scope of claimed methods by the
`
`disclosure of instant specification.
`
`Exhibit 2008 Page 013
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 12
`
`Double Patenting
`
`The nonstatutory double patenting rejection is based on a judicially created
`doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the
`unjustified or improper timewise extension of the "right to exclude" granted by a patent
`and to prevent possible harassment by multiple assignees. A nonstatutory
`obviousness-type double patenting rejection is appropriate where the conflicting claims
`are not identical, but at least one examined application claim is not patentably distinct
`from the reference claim(s) because the examined application claim is either anticipated
`by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140
`F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29
`USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir.
`1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422
`F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163
`USPQ 644 (CCPA 1969).
`A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d)
`may be used to overcome an actual or provisional rejection based on a nonstatutory
`double patenting ground provided the conflicting application or patent either is shown to
`be commonly owned with this application, or claims an invention made as a result of
`activities undertaken within the scope of a joint research agreement.
`Effective January 1, 1994, a registered attorney or agent of record may sign a
`terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with
`37 CFR 3.73(b).
`
`Claims 131, 132, 134-149 are provisionally rejected on the ground of
`
`nonstatutory obviousness-type double patenting as being unpatentable over claims 1,
`
`16. 17 of copending Application No. 13153291 in view of PRNewswire (Dec 2009) and
`
`Pollyea et al. (Poster Abstracts, Dec 3 2009, 5 1"s ASH Annual Meeting and Exposition)
`
`and further in view of Hiddeman et al. (Seminars in Oncology, 30, 1, 2, Feb 2003, p 16-
`
`20).
`
`The instant application claims a method of treating hematological malignancy
`
`such as relapsed or refractory diffuse large B-cell lymphoma, relapsed or refractory
`
`mantle cell lymphoma comprising administering a Btk inhibitor compound such as the
`
`Exhibit 2008 Page 014
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 13
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`elected species (1 -[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1 H-pyrazolo[3,4-d]pyrimidin-
`
`1-yl]-1-piperidinyl]- 2-Propen-1-one)( PCl-32765).
`
`The co-pending application '291 teaches a method of treating diffuse large B-cell
`
`lymphoma comprising administering the same elected compound (PCI-32765).
`
`'291 do not explicitly teach the use of the elected species in the treatment of
`
`relapsed or refractory non-Hodgkin's lymphoma or the specific dosage amounts as
`
`claimed.
`
`PRNewswire document discusses the multi-center dose escalation Phase I trial
`
`of orally administered Bruton's tyrosine kinase (Btk) inhibitor PCl-32765 in patients with
`
`relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) or chronic lymphocytic
`
`leukemia (CLL) (see para 1). Also, the document states that "PCl-32765 appears to be
`
`well tolerated by patients at oral doses that are able to fully inhibit the enzyme Btk," (see
`
`para 7). Also, the reference teaches patients with mantle cell lymphoma is given
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`treatment (see para 3).
`
`Poster Abstract document teaches PCl-32675 is an oral, potent and selective
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`covalent inhibitor of Btk, inhibits tumor growth in B-cell non-Hodgkin's lymphoma
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`models and reports the preliminary results of the first-in-human study with the agent.
`
`The reference further teach that the patients with relapsed or refractory B-cell NHL have
`
`been enrolled and was given a dose of 1.25 mg/kg/day to 17.5 mg/kg/day, two patient
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`with MCL (mantle cell lymphoma) have been enrolled and PCl-32765 is a novel agent
`
`which targets Btk and appears to be well tolerated.
`
`Exhibit 2008 Page 015
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 14
`
`A person of ordinary skill in the art at the time of the invention would have found
`
`it obvious to use the elected species (1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1 H-
`
`pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]- 2-Propen-1-one) in treating refractory or
`
`relapsed B-cell lymphoma including mantle cell lymphoma from the teachings of the co-
`
`pending application, PRNewswire document and the poster abstract. Regarding the
`
`limitations of the claims 140-144, the co-pending teaches the same compound as
`
`claimed and hence will have the same properties as achemical composition and its
`
`properties are inseparable. Regarding the dosage regimen limitations in the claims 134-
`
`136, dosage regimen is clearly a result effective parameter that is within the skill of an
`
`ordinary artisan. Hence it would have been obvious to a person of ordinary skill in the
`
`art to adjust the dosage regimen according to the specific treatment(s).
`
`The references do not explicitly teach the second cancer agent rituximab (elected
`
`species) in the treatment.
`
`Hiddeman et al. teaches that rituximab is effective in both previously untreated
`
`and relapsed or refractory indolent non-Hodgkin's lymphoma; in combination with
`
`chemotherapy rituximab has achieved response rates higher than 90% with long
`
`duration of remission in phase II studies. Furthermore the reference teaches that
`
`rituximab in a combination therapy in the treatment of relapsed or refractory mantle cell
`
`lymphoma has provided striking results. The reference discloses that patients with
`
`relapsed or refractory MCL (40) were recruited for the study and the superiority of
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`rituximab with FCM was particularly striking for patients with MCL with an ORR of 65%
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`(See p 17, col. 1, para 1, lines 1-3, 12, col. 2, para 1, lines 19-23, Table 3).
`
`Exhibit 2008 Page 016
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 15
`
`Thus a person of ordinary skill in the art at the time of the invention would have
`
`found it obvious from the studies of Hiddeman that the same agent (here rituximab) can
`
`be used to treat previously untreated non-Hodgkin's lymphoma and relapsed or
`
`refractory indolent non-Hodgkin's lymphoma. Also it would have been obvious from the
`
`studies of Hiddeman that rituximab in combination therapy is effective in treating
`
`relapsed or refractory mantle cell lymphoma. A person of ordinary skill in the art at the
`
`time of the invention would have been motivated to use the elected species in treating
`
`the elected condition in expectation of achieving therapeutic benefits. A person of
`
`ordinary skill in the art at the time of the invention would have been motivated to
`
`combine the elected species with rituximab in treating relapsed or refractory mantle cell
`
`lymphoma in expectation of success and in expectation of achieving synergistic or
`
`additive therapeutic benefits.
`
`This is a provisional obviousness-type double patenting rejection because the
`
`conflicting claims have not in fact been patented.
`
`Claims 131, 132, 134-139, 145-149 are provisionally rejected on the ground of
`
`nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 2,
`
`5-7, 15, 24, 25, 29, 30, 33, 34, 36, 37, 48-58 of copending Application No. 13153317.
`
`Although the conflicting claims are not identical, they are not patentably distinct
`
`from each other because both the instant application and the co-pending application
`
`claims a method of treating hematological malignancy including relapsed or refractory
`
`lymphomas (e.g. mantle cell lymphoma, claim 25) comprising administering a Btk
`
`Exhibit 2008 Page 017
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 16
`
`inhibitor compound such as the elected species (1-[(3R)-3-[4-amino-3-(4-
`
`phenoxyphenyl)-1 H-pyrazolo[3,4-d]pyrimidin-1-yl]-l -piperidinyl]- 2-Propen-1-one).
`
`This is a provisional obviousness-type double patenting rejection because the
`
`conflicting claims have not in fact been patented.
`
`Claim Rejections - 35 USC § 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
`
`obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set
`forth in section 102 of this title, if the differences between the subject matter sought to be patented and
`the prior art are such that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said subject matter pertains.
`Patentability shall not be negatived by the manner in which the invention was made.
`
`The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148
`
`USPQ 459 (1966), that are applied for establishing a background for determining
`
`obviousness under 35 U.S.C. 103(a) are summarized as follows:
`
`1.
`2.
`3.
`4.
`
`Determining the scope and contents of the prior art.
`Ascertaining the differences between the prior art and the claims at issue.
`Resolving the level of ordinary skill in the pertinent art.
`Considering objective evidence present in the application indicating
`obviousness or nonobviousness.
`
`This application currently names joint inventors. In considering patentability of
`
`the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of
`
`the various claims was commonly owned at the time any inventions covered therein
`
`were made absent any evidence to the contrary. Applicant is advised of the obligation
`
`under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was
`
`not commonly owned at the time a later invention was made in order for the examiner to
`
`Exhibit 2008 Page 018
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 17
`
`consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g)
`
`prior art under 35 U.S.C. 103(a).
`
`Claims 131, 132, 134-149 are rejected under 35 U.S.C. 103(a) as being
`
`unpatentable over Honigberg et al (US 2008/0076921, already of record) in view of
`
`PRNewswire (Dec 2009) and Pollyea et al. (Poster Abstracts, Dec 3 2009, 51" ASH
`
`Annual Meeting and Exposition) and further in view of Hiddeman et al. (Seminars in
`
`Oncology, 30, 1, 2, Feb 2003, p 16-20).
`
`Claims 131, 132, 134-149 are drawn towards a method for treating a relapsed or
`
`refractory hematological malignancy in an individual comprising administering to the
`
`individual an inhibitor of Bruton's tyrosine kinase (Btk). The elected species is
`
`i,
`
`-h
`
`Honigberg teaches the following compound (p 24, [252]).
`
`(S ,
`
`~ \
`
`Exhibit 2008 Page 019
`
`

`

`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 18
`
`Honigberg et al. discloses that the compositions comprising this compound may
`
`be used in the treatment of d