Coalition for Affordable Drugs IV LLC – Exhibit 1018
`
`

`
`Application No.
`13/340,522
`
`Applicant(s)
`BUGGY ET AL.
`
`Office Action Summary
`
`Examiner
`UMAMAHESWARI
`RAMACHANDRAN
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address -(cid:173)
`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE .J. MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
`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.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`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).
`
`Art Unit
`1627
`
`AIA (First Inventor to File)
`Status
`No
`
`Status
`1)~ Responsive to communication(s) filed on 911712013.
`0 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on __ .
`2a)~ This action is FINAL.
`2b)0 This action is non-final.
`3)0 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.
`4)0 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 G.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`5)~ Claim(s) 131. 132. 134-140. 143. 144 and 146-149 is/are pending in the application.
`5a) Of the above claim(s) __ is/are withdrawn from consideration.
`6)0 Claim(s) __ is/are allowed.
`7)~ Claim(s) 131. 132. 134-140. 143. 144 and 146-149 is/are rejected.
`8)0 Claim(s) __ is/are objected to.
`9)0 Claim(s) __ are subject to restriction and/or election requirement.
`* 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
`http://www.uspto.aov/patents/init events/pph/index.jsp or send an inquiry to PPHfeedback@uspto.gov.
`
`Application Papers
`10)0 The specification is objected to by the Examiner.
`11 )0 The drawing(s) filed on __ is/are: a)O accepted or b)O objected to by the Examiner.
`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)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`a)O All b)O Some* c)O None of the:
`Certified copies of the priority documents have been received.
`1.0
`Certified copies of the priority documents have been received in Application No. __ .
`2.0
`Copies of the certified copies of the priority documents have been received in this National Stage
`3.0
`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) 0 Notice of References Cited (PT0-892)
`
`2) ~ Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date __ .
`
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 08-13)
`
`3) 0 Interview Summary (PT0-413)
`Paper No(s)/Mail Date. __ .
`4) 0 Other: __ .
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20131021
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 2
`
`The present application is being examined under the pre-AIA first to invent
`
`provisions.
`
`DETAILED ACTION
`
`The office acknowledges Applicants' response to the office action dated
`
`3/13/2013. Claims 1-130, 133, 141, 142, 145 have been cancelled. Claims 131, 132,
`
`134-140, 143, 144, 146-149 are pending. The claims 131, 132, 134-140, 143, 144, 146-
`
`149 are examined to the extent they read on the elected species.
`
`Applicants' have amended the Specification to comply with the sequence rules.
`
`Applicants' amendment to claim 131 necessitated the withdrawal of 112(1) rejection.
`
`Applicants' arguments regarding the ODP and 103 rejections have been fully
`
`considered but found not to be persuasive. The arguments are addressed in the
`
`Response to Arguments section below. New ODP rejections over 13/747,519 (case
`
`docketed to the examiner on 7/17/2013, after non-final mailed on 3/13/2013) and
`
`13/736,812 (case docketed to the examiner on 4/29/2013, after non-final mailed on
`
`3/13/2013) are made. Applicants' amendments to the claims necessitated the modified
`
`rejections in this action. Accordingly the action is made Final.
`
`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.
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 3
`
`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
`
`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, 134-140, 143, 144, 146-149 are rejected under35 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 st 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, 134-140, 143, 144, 146-149 are drawn towards a method for
`
`treating a relapsed or refractory hematological malignancy in an individual comprising
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 4
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`administering to the individual a therapeutically effective amount of an inhibitor of
`
`Bruton's tyrosine kinase (Btk) having the following structure.
`
`Applicants elected the species of lymphoma - mantle cell lymphoma (MCL), species of
`
`second cancer agent - rituximab (174722-31-7).
`
`Honigberg teaches the following compound (p 24, [252]).
`
`Honigberg et al. discloses that the compositions comprising this compound may
`
`be used in the treatment of disease or conditions that would benefit from inhibition of
`
`Bruton's tyrosine kinase or a homolog thereof which involves the administration of the
`
`composition in therapeutically effective amounts to the subject wherein the subject is
`
`human and the administration is oral ([0027-0029]) wherein the subject in need is
`
`suffering from a cancer, which is B-cell proliferative disorder, e.g., diffuse large B cell
`
`lymphoma, follicular lymphoma, chronic lymphocytic lymphoma, chronic lymphocytic
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 5
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`leukemia, B-cell prolymphocytic leukemia and a B-cell proliferative disorder such as
`
`plasma cell myeloma ([0036], reference claims 19- 20, [0425]. Honigberg et al. teaches
`
`that the methods for the treatment of cancer comprise administering a compound of
`
`formula D for hematological cancers [0048]. Honigberg et al. discloses single
`
`administrations of the effective amount of their inventive compound (includes instantly
`
`elected compound), in which (i) the compound is administered once; (ii) the compound
`
`is administered to the mammal multiple times over the span of one day; (iii) continually;
`
`or (iv) continuously [0054-0055]. Honigberg et al further discloses treatment of
`
`proliferative disorders, including cancer, with their compounds to further comprise
`
`administering at least one additional agent which includes alemtuzumab, arsenic
`
`trioxide, asparaginase (pegylated or non), bevacizumab, cetuximab, platinum-based
`
`compounds such as cisplatin, cladribine, daunorubicin/doxorubicin/idarubicin,
`
`irinotecan, fludarabine, 5-fluorouracil, gemtuzumab, methotrexate, Paclitaxel.TM., taxol,
`
`temozolomide, thioguanine, ( [0057] and [0418-0427]). Honigberg et al discloses a
`
`method for treating a cancer comprising administering to a subject in need thereof a
`
`composition containing a therapeutically effective amount of the instantly claimed
`
`compound that forms a covalent bond with a cysteine side chain of a Burton's tyrosine
`
`kinase where in the cysteine is cysteine 481 in Btk (reference claim 18-21, [0185]
`
`[0470]). Honigberg teaches that the amount of a given agent will vary depending upon
`
`factors such as disease or condition and its severity, the condition being treated etc.
`
`and doses employed for adult human treatment will typically be in the range of 0.02-
`
`5000 mg per day, or from about 1-1500 mg per day (see [041 O]).
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 6
`
`Honigberg et al. fails to disclose the B-cell proliferative disorder as a relapsed or
`
`refractory non-Hodgkin's lymphoma (relapsed or refractory mantle cell lymphoma -
`
`elected disorder) or the dosage amounts of the compound 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 in the study
`
`(see para 3). Also, it is taught in the document that 'new drug or biological candidates
`
`targeting B-cells, including Rituxan (rituximab) for lymphomas and rheumatoid arthritis,
`
`are aimed at eliminating abnormally functioning B-cells' (para 9, last two lines).
`
`Poster Abstract document teaches PCl-32675 is an oral, potent and selective
`
`covalent inhibitor of Btk, inhibits tumor growth in B-cell non-Hodgkin's lymphoma
`
`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
`
`with MCL (mantle cell lymphoma) have been enrolled and PCl-32765 is a novel agent
`
`which targets Btk and appears to be well tolerated.
`
`A person of ordinary skill in the art at the time of the invention would have found
`
`it obvious to use the compound of claim 131 in treating refractory or relapsed diffuse
`
`large B-cell lymphoma from the teachings of the Honigberg et al. and PRNewswire
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 7
`
`document. A person of ordinary skill in the art at the time of the invention would have
`
`been motivated to use the compound in a method of treating a hematological
`
`malignancy such as relapsed or refractory B-cell non-Hodgkin's lymphoma in
`
`expectation of success and in expectation of achieving therapeutic benefits. Regarding
`
`the limitation of effective therapeutic amount, Applicants state that the amount of the
`
`irreversible Btk inhibitor can range from about 300 mg/day up to and including 1000
`
`mg/day and the amounts will depend on the severity and course of the disease or
`
`condition or previous therapy etc. (see [00479]) and doses employed for adult treatment
`
`will typically be in the range of 0.02-5000 mg/day or 1-1500 mg/day (see [00485], p
`
`154). Honigberg teaches that the amount of a given agent will vary depending upon
`
`factors such as disease or condition and its severity, the condition being treated etc.
`
`and doses employed for adult human treatment will typically be in the range of 0.02-
`
`5000 mg per day, or from about 1-1500 mg per day (see [041 O]). A person of ordinary
`
`skill in the art at the time of the invention would have found it obvious to use
`
`concentrations as taught in the instant specification and such doses would have been
`
`therapeutically effective because Honigberg teaches the same dosage amounts can be
`
`employed.
`
`Regarding the limitations of 'irreversible covalent inhibitor of Btk' in claims 148
`
`and 149, the same compound is taught by Honigberg. Any properties exhibited by or
`
`benefits provided by the composition are inherent and are not given patentable weight
`
`over the prior art. A chemical composition and its properties are inseparable. Therefore,
`
`if the prior art teaches the identical chemical structure, the properties of the compound
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 8
`
`Applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705,
`
`709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
`
`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
`
`rituximab with FCM was particularly striking for patients with MCL with an ORR of 65%
`
`(See p 17, col. 1, para 1, lines 1-3, 12, col. 2, para 1, lines 19-23, Table 3).
`
`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 combine the compound of claim 131
`
`with rituximab in treating relapsed or refractory mantle cell lymphoma in expectation of
`
`success and in expectation of achieving synergistic or additive therapeutic benefits.
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 9
`
`With regards to the functional limitation set forth in instant claim 140 wherein
`
`>95% of the Btk is occupied by the inhibitor of Btk at 4 hours post dose, Honigberg
`
`discloses the active step instantly claimed which the method of treating B-Cell
`
`lymphoproliferative disorders such as diffuse large B cell lymphoma, follicular
`
`lymphoma, chronic lymphocytic lymphoma with an Btk inhibitor which is the same as the
`
`instantly claimed compound, which inhibits Btk irreversibly by forming a covalent bond
`
`to the cysteine 481 of the Burton's tyrosine kinase and accordingly, the functional
`
`limitations set forth in the instant application will be achieved. It is noted that In re Best
`
`(195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections
`
`wherein the prior art discloses subject matter which there is reason to believe inherently
`
`includes functions that are newly cited or is identical to a product instantly claimed. In
`
`such a situation the burden is shifted to the applicants to "prove that subject matter
`
`shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594,
`
`second column, first full paragraph). It is also noted that, "[T]he discovery of a previously
`
`unappreciated property of a prior art composition, or of a scientific explanation for the
`
`prior art's functioning, does not render the old composition patentably new to the
`
`discoverer." Atlas Powder Co. v. lreco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943,
`
`1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown
`
`property which is inherently present in the prior art does not necessarily make the claim
`
`patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430,433 (CCPA 1977). See
`
`also MPEP § 2112.01 with regard to inherency and product-by-process claims.
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 1 O
`
`In addition, it is also noted that "Products of identical chemical composition
`
`cannot have mutually exclusive properties." A chemical composition and its properties
`
`are inseparable. Therefore, if the prior art teaches the identical chemical structure, the
`
`properties applicant discloses and/or claims are necessarily present. In re Spada, 911
`
`F.2d 705,709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). As such the instantly claimed
`
`mechanistic functions of the instantly claimed compound to occupy 95% of Btk at 4
`
`hours post dose would be present in the method taught by Honigberg et al. And the
`
`compound would therefore elicit these effects whenever it is administered. Therefore
`
`the instant claims would have been obvious over the teachings of Honigberg in view of
`
`PRNewswire, Poster Abstract document and Hiddeman et al.
`
`Response to Arguments
`
`Applicants' argue that the cited references either alone or in combination, fail to
`
`teach, suggest or otherwise provide a reason for each and every element of the claims
`
`as amended herein.
`
`In response, Honigberg teaches a genus of compound of formula (D) and further
`
`explicitly claims the compound of claim 131 of the instant application.
`
`o-0
`I 17', .
`
`.
`
`~­"
`
`~)-~)-r
`
`(formula D, claim 21)
`
`0
`
`(formula F, claim 23)
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 11
`
`Honigberg, teaches the compounds of formula (D) (which inlcudes the compound
`
`of claim 131 of the instant application) is useful in treating B-cell proliferative disorder
`
`such as chronic lymphocytic lymphoma, diffuse large B cell lymphoma, follicular
`
`lympohom or chronic lymphocytic leukemia. Honigberg teach the compounds of formula
`
`Dare useful in treating cancer and the cancer is a B-cell proliferative disorder, e.g.,
`
`diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic lymphoma,
`
`chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic
`
`lymphoma/Waldenstrom macroglobulinemia, splenic marginal zone lymphoma, plasma
`
`cell myeloma, plasmacytoma, extranodal marginal zone B cell lymphoma, nodal
`
`marginal zone B cell lymphoma, mantle cell lymphoma, mediastinal (thymic) large B cell
`
`lymphoma, intravascular large B cell lymphoma, primary effusion lymphoma, burkitt
`
`lymphoma/leukemia, or lymphomatoid granulomatosis (see 0033). Honigberg explicitly
`
`teach the compound of claim 131 and further teach that it exhibits significant selectivity
`
`for Btk in cellular assays (seep 65, col. 1, lines 11-12).
`
`In fact, Applicants in the Specification disclose that the hematological malignancy
`
`is a B-cell malignancy, hematological malignancy is a leukemia, lymphoproliferative
`
`disorder or myeloid (see [0004], lines 11-13, published application) and specifically the
`
`hematological malignancy is a chronic lymphocytic leukemia (CLL), small lymphocytic
`
`lymphoma (SLL), high risk CLL, or a non-CLUSLL lymphoma (lines) and the
`
`hematological malignancy is 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
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 12
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`multiple myeloma (see lines 51-59, col. 2, [0004], published application also; also see
`
`Applicants claim 146, 148)
`
`From Honigberg's teachings a person of ordinary skill in the art at the time of the
`
`invention would have found it obvious that the compounds of formula D are useful in
`
`treating cancer in general, e.g. B cell proliferative disorder including mantle cell
`
`lymphoma or chronic lymphocytic lymphoma. A person of ordinary skill in the art at the
`
`time of the invention from Honigberg's teaching alone would have found it obvious to try
`
`and use the compound of claim 131 in treating a B cell proliferative disorder such as
`
`mantle cell lymphoma because (1) Honigberg explicitly teach the compound of claim
`
`131 and further teach that it exhibits significant selectivity for Btk in cellular assays (see
`
`p 65 ,col. 1, lines 11-12). From Honigberg's teachings alone, a person of ordinary skill in
`
`the art at the time of the invention would have found it obvious to try and use the
`
`compound claimed in treating relapsed or refractory mantle cell lymphoma. Regarding
`
`the dosages, Honigberg teach 0.02-5000 mg per day, or from about 1-1500 mg per day
`
`and Applicants in the specification disclose that doses employed for adult treatment will
`
`typically be in the range of 0.02-5000 mg/day or 1-1500 mg/day. A person of ordinary
`
`skill in the art at the time of the invention would have found it obvious to use
`
`concentrations as taught in the instant specification and such doses would have been
`
`therapeutically effective because Honigberg teaches the same dosage amounts can be
`
`employed. Hiddeman et al. teaches that rituximab is effective in both previously
`
`untreated and relapsed or refractory non-Hodgkin's lymphoma. From Honigberg and
`
`Hiddeman alone a person of ordinary skill in the art the time of the invention would have
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 13
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`found it obvious to use the compound of claim 131 and rituximab in treating relapsed or
`
`refractory non-Hodgkin's lymphoma and relapsed or refractory mantle cell lymphoma is
`
`a species of non-Hodgkin's lymphoma.
`
`Applicants argue that both the PRNewswire and the Poster abstract describe a
`
`compound called PCl-32765 for the treatment of relapsed or refractory NHL. Neither
`
`reference teaches or suggests what PCl-32765 is, nor ascribes any structure to PCI-
`
`32765. In addition, Honigberg does not teach or suggest any compound named PCI-
`
`32765. Hence, in view of the cited references, one of ordinary skill in the art would not
`
`have known what PCl-32765 is other than a covalent Btk inhibitor. One of ordinary skill
`
`in the art would not have known how to obtain PCl-32765 nor generate PCl-32765, let
`
`alone administer PCl-32765 for the treatment of a relapsed or refractory NHL. In
`
`addition, one of ordinary skill in the art would not have known that PCl-32765
`
`represented the compound identified in independent claims 131, 147 and 149 as
`
`pending. Hence, the present claims, for the treatment of relapsed or refractory
`
`hematological malignancies, are not obvious over the combination of Honigberg,
`
`PRNewswire or the Poster abstract.
`
`In response, Honigberg teach the use of Btk inhibitors including the compound of
`
`claim 131 in the treatment of hematological malignancy such as mantle cell lymphoma,
`
`PRNewswire or the Poster abstract references teaches the use of a Btk inhibitor, PCI-
`
`32765 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. A person
`
`of skilled in the art at the time of the invention would have found that PCl-32765 is the
`
`compound of claim 131 because prior to the invention PCl-32765 structure was known.
`
`

`
`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 14
`
`The effective filing date of this application is 6/3/2010. Davis's studies (Nature, Letters,
`
`463, 7 Jan 2010) teach the structure of PCl-32765 as compound 13 of Pan et al.
`
`(ChemMedChem, 2, 58-61, 2006). The secondary references (PRNewswire and the
`
`Poster abstract) does not have to explicitly teach that PCl-32765 is the compound of
`
`claim 131 as it was known in the art, prior to the filing date of this application that PCI-
`
`32765 has the following structure:
`
`It is within the skill of an artisan to obtain the chemical structure of PCl-32765 from other
`
`resources (e.g. research articles) and equate it to the compound of claim 131. Please
`
`note that this is not an introduction of a new reference, only used to add to the rebuttal
`
`by the Examiner to show that the structure of PCl-32765 is known prior to the filing of
`
`the instant application.
`
`Applicants' argue that Hiddeman does not cure the defects of Honigberg,
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`PRNewswire or the Poster abstract. Hiddeman discloses rituximab for the treatment of
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`relapsed or refractory NHL. Hiddeman does not teach or suggest any Btk inhibitor nor
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`does it teach or suggest the administration of a Btk inhibitor, let alone the structure.
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`In response, Hiddeman has been cited as a secondary reference to teach that
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`rituximab is effective in both previously untreated and relapsed or refractory non-
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`

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`Application/Control Number: 13/340,522
`Art Unit: 1627
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`Page 15
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`Hodgkin's lymphoma. A person of ordinary skill in the art at the time of the invention
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`would have found it obvious to use rituximab along with the compound of claim 131 in
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`expectation of achieving therapeutic benefits in treating relapsed or refractory non-
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`Hodgkin's lymphoma such as mantle cell lymphoma.
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`Applicants' argue that the Examiner's conclusion of obviousness is based on
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`improper hindsight reasoning. MPEP § 2142 states that "impermissible hindsight must
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`be avoided and the legal conclusion must be reached on the basis of the facts gleaned
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`from the prior art" (emphasis added). "'Any judgment on obviousness is in a sense
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`necessarily a reconstruction based on hindsight reasoning, but so long as it takes into
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`account only knowledge which was within the level of ordinary skill in the art at the time
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`the claimed invention was made and does not include knowledge gleaned only from
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`applicant's disclosure, such a reconstruction is proper"' (MPEP § 2145(X)(A), quoting In
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`re Mclaughlin, 443 F.2d 1392, 1395 (CCPA 1971 ), (emphasis added).
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`In response, no hindsight reasoning was employed in rejecting the claims over
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`the prior because it must be recognized that any judgment on obviousness is in a sense
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`necessarily a reconstruction based upon hindsight reasoning. But so long as it takes
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`into account only knowledge which was within the level of ordinary skill at the time the
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`claimed invention was made, and does not include knowledge gleaned only from the
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`applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d
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`1392, 170 USPQ 209 (CCPA 1971 ). Honigberg is relied upon for the reasons stated
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`above. The secondary references PRNewswire and Poster Abstract teach the use of
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`PCl-32765 in relapsed or refractory non-Hodgkin's lymphoma. As stated above the
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`Application/Control Number: 13/340,522
`Art Unit: 1627
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`Page 16
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`structure of PCl-32765 has been known in the art prior to the invention. The secondary
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`does not have to explicitly show or describe the structure because there are other
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`sources (research articles or databases) that can provide the structure and it is within
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`the skill of an artisan to obtain the chemical structure and equate it to the compound of
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`claim 131 (as amended). Thus the claimed invention would have been obvious over the
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`combined teachings of Honigberg, PRNewswire, Poster Abstract and Hiddeman.
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`Double Patenting
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`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 Langi, 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).
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`Claims 131, 132, 134-140, 143, 144, 146-149 are provisionally rejected on the
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`ground of nonstatutory obviousness-type double patenting as being unpatentable over
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`claims 1, 16. 17 of copending Application No. 13153291 in view of PRNewswire (Dec
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`2009) and Pollyea et al. (Poster Abstracts, Dec 3 2009, 51 st ASH Annual Meeting and
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`Application/Control Number: 13/340,522
`Art Unit: 1627
`
`Page 17
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`Exposition) and further in view of Hiddeman et al. (Seminars in Oncology, 30, 1, 2, Feb
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`2003, p 16-20).
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`The instant application claims a method of treating hematological malignancy
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`such as relapsed or refractory diffuse large B-cell lymphoma, relapsed or refractory
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`mantle cell lymphoma comprising administering a Btk inhibitor (1-[(3R)-3-[4-amino-3-(4-
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`phenoxyphenyl)-1 H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]- 2-Propen-1-one ).
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`The co-pending application '291 teaches a method of treating diffuse large B-cell
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`lymphoma comprising administering the compound of claim 131 (see claim 17 of '291 ).
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`'291 do not explicitly teach the use of the claimed species in the treatment of
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`relapsed or refractory non-Hodgkin's lymphoma or the specific dosage amounts as
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`claimed.
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`PRNewswire document discusses the multi-center dose escalation Phase I trial
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`of orally administered Bruton's tyrosine kinase (Btk) inhibitor PCl-32765 in patients with
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`relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) or chronic lymphocytic
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`leukemia (CLL) (see para 1 ). Also, the document states that "PCl-32765 appears to be
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`well tolerated by patients at oral doses that are able to fully inhibit the enzyme Btk," (see
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`para 7). Also, the reference teaches patients with mantle cell lymphoma is given
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`treatment (see para 3).
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`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-Hodgki