UNITED STA 1ES p A 1ENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`14/091,661
`
`11127/2013
`
`Hans-Juergen Krause
`
`110222-0005-303
`
`1026
`
`118276
`7590
`Ropes & Gray, LLP
`1211 Avenue of the Americas
`New York, NY 10036
`
`01/27/2014
`
`EXAMINER
`
`BUNNER, BRIDGET E
`
`ART UNIT
`
`PAPER NUMBER
`
`1647
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`01127/2014
`
`ELECTRONIC
`
`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.
`
`Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
`following e-mail address(es):
`USPatentMai1@ropesgray.com
`USPatentMai12@ropesgray.com
`
`PTOL-90A (Rev. 04/07)
`
`Ex. 2010-0001
`
`

`
`Application No.
`14/091 ,661
`
`Applicant(s)
`KRAUSE ET AL.
`
`Examiner
`Bridget E. Bunner
`
`Art Unit
`1647
`
`Office Action Summary
`
`AlA (First Inventor to File)
`Status
`No
`-- The MAILING DATE 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. MONTHS FROM THE MAILING DATE OF
`THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR t. t 36(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. § t33).
`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 t .704(b).
`
`Status
`1 )~ Responsive to communication(s) filed on 03 Januarv 2014.
`0 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on __ .
`2a)0 This action is FINAL.
`2b)~ 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 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims*
`5)~ Claim(s) 1-10 and 12-31 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) 1-10 and 12-31 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://vvww.uspto.gov/patents/init events/pph/index.jsp or send an inquiry to P~'Hfeedback(wuspto.oov.
`
`Application Papers
`1 0)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/08a and/or PTO/SB/08b)
`Paper No(s)/Mail Date 11127113.
`
`3) 0 Interview Summary (PT0-413)
`Paper No(s)/Mail Date. __ .
`4) 0 Other: __ .
`
`U.S. Patent and Trademark Off1ce
`PTOL-326 (Rev. t t-t3)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20t 40t t 5
`
`Ex. 2010-0002
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 2
`
`DETAILED ACTION
`
`The present application is being examined under the pre-AlA first to invent provisions.
`
`Status of Application, Amendments and/or Claims
`
`The amendment of 03 January 2014 has been entered in full. Claims 1, 9, 10, 14, 16, 17,
`
`19-21, 28, and 29 are amended. Claim 10 is cancelled. Claim 31 is added.
`
`Claims 1-10 and 12-31 are under consideration in the instant application.
`
`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 double patenting rejection is appropriate
`
`where the claims at issue 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 CPR 1.32l(c) or 1.32l(d) may
`
`be used to overcome an actual or provisional rejection based on a nonstatutory double patenting
`
`ground provided the reference 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. A terminal disclaimer must be signed in compliance with 37 CPR
`
`1.32l(b).
`
`Ex. 2010-0003
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 3
`
`The USPTO internet Web site contains terminal disclaimer forms which may be used.
`
`Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what
`
`form should be used. A web-based eTerminal Disclaimer may be filled out completely online
`
`using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and
`
`approved immediately upon submission. For more information about eTerminal Disclaimers,
`
`refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
`
`1.
`
`Claims 1-10 and 12-31 are rejected on the ground of nonstatutory double patenting as
`
`being unpatentable over claims 1-19 of U.S. Patent No. 8,216,583. Although the claims at issue
`
`are not identical, they are not patentably distinct from each other because both sets of claims are
`
`directed to a stable liquid aqueous pharmaceutical formulation comprising an anti-human tumor
`
`necrosis factor alpha (TNFa) antibody or antigen-binding fragment thereof at a concentration of
`
`20 to 150 mg/ml, a polyol, a surfactant, and a buffer system having a pH of 4 to 8.
`
`Claim 1 of the instant application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
`
`polyol, (c) a surfactant, and (d) a buffer system having a pH of 4 to 8, wherein the antibody
`
`comprises a light chain variable region comprising the light chain complementarity determining
`
`region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the
`
`heavy chain CDR1, CDR2, and CDR3 of D2E7. Claim 4 of the instant application recites that
`
`the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 and the
`
`heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 2.
`
`Meanwhile, claim 1 of the '583 patent is directed to a stable liquid aqueous formulation a
`
`human anti-Tumor Necrosis Factor alpha (TNFa) antibody, or antigen-binding fragment
`
`Ex. 2010-0004
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 4
`
`thereof, at a concentration of between about 20 and about 150 mg/ml, a polyol, a surfactant, and
`
`a buffer system comprising citrate and phosphate, wherein said formulation has a pH of about 4
`
`to about 8, and wherein the antibody, or antigen-binding portion thereof, comprises a light chain
`
`variable region comprising a complementary determining region (CDR) 1 domain comprising
`
`the amino acid sequence set forth in SEQ ID N0:7; a CDR2 domain comprising the amino acid
`
`sequence set forth in SEQ ID N0:5; and a CDR3 domain comprising the amino acid sequence
`
`set forth in SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at
`
`position 1, 4, 5, 7, or 8, or by one to five conservative amino acid substitutions at positions 1, 3,
`
`4, 6, 7, 8, and/or 9; and comprises a heavy chain variable region comprising a CDR1 domain
`
`comprising the amino acid sequence set forth in SEQ ID N0:8; a CDR2 domain comprising the
`
`amino acid sequence set forth in SEQ ID N0:6; and a CDR3 domain comprising the amino acid
`
`sequence set forth in SEQ ID NO: 4, or modified from SEQ ID NO: 4 by a single alanine
`
`substitution at position 2, 3, 4, 5, 6, 8, 9, 10, or 11, or by one to five conservative amino acid
`
`substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11, and/or 12. Claims 3 and 14 of the '583 patent
`
`recite that the antibody or antigen-binding portion thereof comprises a light chain variable
`
`region comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region
`
`comprising the amino acid sequence of SEQ ID NO: 2.
`
`The pH of the buffer system/formulation and the concentrations of the antibody, mannitol
`
`(a polyol), and polysorbate 80 are the same in both claim sets. The light chain variable region
`
`of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2 recited in the instant
`
`claims and in the claims of the '583 patent are identical. The D2E7 antibody recited in the
`
`instant claims comprises the light chain variable region CDR1 (SEQ ID NO: 7), CDR2 (SEQ ID
`
`Ex. 2010-0005
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 5
`
`NO: 5), and CDR3 (SEQ ID NO: 3) and the heavy chain variable region CDR1 (SEQ ID NO:
`
`8), CDR2 (SEQ ID NO: 6), and CDR3 (SEQ ID NO: 4) as recited in the claims of the '583
`
`patent (see amino acids 24-34; 50-56; and 89-97 of SEQ ID NO: 1 of the instant application; see
`
`amino acids 31-35; 50-65; and 99-110 of SEQ ID NO: 2 of the instant application).
`
`One of the only differences between the two claim sets is that the product claims of the
`
`instant application are broader than those of the '583 patent because the instant claims only
`
`recite a "buffer system". The claims of the '583 patent recite that the buffer system comprises
`
`citrate and phosphate. The instant claims also recite that the formulation comprises a human
`
`IgG 1 anti-human TNF a antibody while the patented claims do not specifically recite "IgG 1 ".
`
`However, the disclosure of the '583 patent clearly indicates that the antibody may be IgG 1
`
`(column 5, lines 1-4).
`
`Furthermore, although many of the claims of the '583 patent broadly recite "a polyol" as
`
`a component of the pharmaceutical formulation, while claims 10 and 31 of the instant
`
`application recite that the polyol is trehalose, the specification of the '583 patent discloses
`
`trehalose as an example in the definition for polyol (see column 7, lines 48-66).
`
`It is noted that
`
`the specification can be used as a dictionary to learn the meaning of a term in the patent claim
`
`(Taro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir.
`
`1999); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250, 48 USPQ2d 1117,
`
`1122 (Fed. Cir. 1998)).
`
`2.
`
`Claims 1-10 and 12-31 are provisionally rejected on the ground of nonstatutory double
`
`patenting as being unpatentable over claims 1, 3-5, 9, 12, and 14-31 of copending Application
`
`Ex. 2010-0006
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 6
`
`No. 13/471,820. Although the claims at issue are not identical, they are not patentably distinct
`
`from each other because both sets of claims are directed to a stable liquid aqueous
`
`pharmaceutical formulation comprising an anti-human tumor necrosis factor alpha (TNFa)
`
`antibody or antigen-binding fragment thereof, a polyol, a surfactant, and a buffer system.
`
`Claim 1 of the instant application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
`
`polyol, (c) a surfactant, and (d) a buffer system having a pH of 4 to 8, wherein the antibody
`
`comprises a light chain variable region comprising the light chain complementarity determining
`
`region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the
`
`heavy chain CDR1, CDR2, and CDR3 of D2E7. Claim 4 of the instant application recites that
`
`the light chain variable region comprises the amino acid sequence of SEQ ID NO: 1 and the
`
`heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 2.
`
`Meanwhile, claim 1 of the '820 application, for example, is directed to a stable liquid
`
`aqueous pharmaceutical formulation having a pH of about 4.5 to about 6, comprising an isolated
`
`human IgG1 anti-Tumor Necrosis Factor alpha (TNFa) antibody, or antigen-binding fragment
`
`thereof, at a concentration of 35-115 mg/ml, a polyol, a surfactant, and a buffer system
`
`comprising citrate and phosphate, wherein the antibody, or antigen-binding portion thereof,
`
`comprises a light chain variable region comprising a complementary determining region (CDR)
`
`1 domain comprising the amino acid sequence set forth in SEQ ID N0:7; a CDR2 domain
`
`comprising the amino acid sequence set forth in SEQ ID N0:5; and a CDR3 domain comprising
`
`the amino acid sequence set forth in SEQ ID NO: 3; and comprises a heavy chain variable region
`
`Ex. 2010-0007
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 7
`
`comprising a CDRl domain comprising the amino acid sequence set forth in SEQ ID N0:8; a
`
`CDR2 domain comprising the amino acid sequence set forth in SEQ ID N0:6; and a CDR3
`
`domain comprising the amino acid sequence set forth in SEQ ID NO: 4. Claims 9, 23, and 24 of
`
`the '820 application recite that the antibody or antigen-binding portion thereof comprises a light
`
`chain variable region comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain
`
`variable region comprising the amino acid sequence of SEQ ID NO: 2.
`
`The pH of the buffer system/formulation and the concentrations of the antibody, mannitol
`
`(a polyol), and polysorbate 80 are the same or overlapping in both claim sets. The light chain
`
`variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2 recited
`
`in the instant claims and in the claims of the '820 application are identical. The D2E7 antibody
`
`recited in the instant claims comprises the light chain variable region CDR1 (SEQ ID NO: 7),
`
`CDR2 (SEQ ID NO: 5), and CDR3 (SEQ ID NO: 3) and the heavy chain variable region CDR1
`
`(SEQ ID NO: 8), CDR2 (SEQ ID NO: 6), and CDR3 (SEQ ID NO: 4) as recited in the claims of
`
`the '820 application (see amino acids 24-34; 50-56; and 89-97 of SEQ ID NO: 1 of the instant
`
`application; see amino acids 31-35; 50-65; and 99-110 of SEQ ID NO: 2 of the instant
`
`application).
`
`One of the only differences between the two claim sets is that the product claims of the
`
`instant application are broader than those of the '820 application because the instant claims only
`
`recite a "buffer system". The claims of the '820 application recite that the buffer system
`
`comprises citrate and phosphate. Furthermore, although many of the claims of the '820
`
`application broadly recite "a polyol" as a component of the pharmaceutical formulation, while
`
`claims 10 and 31 of the instant application recite that the pol yol is trehalose, the specification of
`
`Ex. 2010-0008
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 8
`
`the '583 patent discloses trehalose as an example in the definition for polyol (see column 7,
`
`lines 48-66). It is noted that the specification can be used as a dictionary to learn the meaning
`
`of a term in the patent claim (Taro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53
`
`USPQ2d 1065, 1067 (Fed. Cir. 1999); Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d
`
`1243, 1250,48 USPQ2d 1117, 1122 (Fed. Cir. 1998)).
`
`This is a provisional nonstatutory double patenting rejection because the patentably
`
`indistinct claims have not in fact been patented.
`
`3.
`
`Claims 1-10, 12-31 are provisionally rejected on the ground of nonstatutory double
`
`patenting as being unpatentable over claims 1-30 of copending Application No. 14/091,888.
`
`Although the claims at issue are not identical, they are not patentably distinct from each other
`
`because both sets of claims are directed to a stable liquid aqueous pharmaceutical formulation
`
`comprising a human IgG 1 anti-human tumor necrosis factor alpha (TNFa) antibody or antigen-
`
`binding fragment thereof at a concentration of 20 to 150 mg/ml, a polyol, a surfactant, and a
`
`buffer system having a pH of 4 to 8.
`
`Claim 1 of the instant application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
`
`polyol, (c) a surfactant, and (d) a buffer system having a pH of 4 to 8, wherein the antibody
`
`comprises a light chain variable region comprising the light chain complementarity determining
`
`region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the
`
`Ex. 2010-0009
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 9
`
`heavy chain CDRl, CDR2, and CDR3 ofD2E7. Claims 8, 19, 20, 27, and 31 recite that the
`
`polyol is mannitol. Claims 10 and 31 recite that the polyol is trehalose.
`
`Claim 1 of the '888 application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
`
`polyol, (c) a surfactant, and (d) a buffer system comprising acetate and having a pH of 4 to 8,
`
`wherein the antibody comprises a light chain variable region comprising the light chain
`
`complementarity determining region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain
`
`variable region comprising the heavy chain CDR1, CDR2, and CDR3 of D2E7. Claim 8 recites
`
`that the polyol is mannitol. Claims 11, 19-21, 27 recite that the polyol is trehalose.
`
`The pH of the buffer system/formulation and the concentrations of the antibody, polyol,
`
`and polysorbate 80 are the same in both claim sets. The human IgG 1 anti-human tumor necrosis
`
`factor alpha (TNFa) antibody or antigen-binding fragment thereof is also identical in both the
`
`instant application and the '888 application.
`
`One difference between the two claim sets is that the claims of the instant application
`
`broadly recite a buffer system that has a pH of 4 to 8 while the claims of the '888 application
`
`recite that the buffer system comprises acetate and has a pH of 4 to 8. Thus, the claims of the
`
`'888 application are species claims that anticipate the genus claims of the instant application.
`
`This is a provisional nonstatutory double patenting rejection because the patentably
`
`indistinct claims have not in fact been patented.
`
`Ex. 2010-0010
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 10
`
`4.
`
`Claims 1-10, 12-31 are provisionally rejected on the ground of nonstatutory double
`
`patenting as being unpatentable over claims 1-31 of copending Application No. 14/091,938.
`
`Although the claims at issue are not identical, they are not patentably distinct from each other
`
`because both sets of claims are directed to a stable liquid aqueous pharmaceutical formulation
`
`comprising a human IgG 1 anti-human tumor necrosis factor alpha (TNFa) antibody or antigen-
`
`binding fragment thereof at a concentration of 20 to 150 mg/ml, a polyol, a surfactant, and a
`
`buffer system having a pH of 4 to 8.
`
`Claim 1 of the instant application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
`
`polyol, (c) a surfactant, and (d) a buffer system having a pH of 4 to 8, wherein the antibody
`
`comprises a light chain variable region comprising the light chain complementarity determining
`
`region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the
`
`heavy chain CDR1, CDR2, and CDR3 ofD2E7. Claims 8, 19, 20, 27, and 31 recite that the
`
`polyol is mannitol. Claims 10 and 31 recite that the polyol is trehalose.
`
`Claim 1 of the '938 application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
`
`polyol, (c) a surfactant, and (d) a buffer system comprising histidine and having a pH of 4 to 8,
`
`wherein the antibody comprises a light chain variable region comprising the light chain
`
`complementarity determining region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain
`
`variable region comprising the heavy chain CDR1, CDR2, and CDR3 of D2E7. Claims 8, 19,
`
`Ex. 2010-0011
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
`
`Page 11
`
`20, 27, and 31 recite that the polyol is mannitol. Claims 10 and 31 recite that the polyol is
`
`trehalose.
`
`The pH of the buffer system/formulation and the concentrations of the antibody, polyol,
`
`and polysorbate 80 are the same in both claim sets. The human IgG 1 anti-human tumor necrosis
`
`factor alpha (TNFa) antibody or antigen-binding fragment thereof is also identical in both the
`
`instant application and the '938 application.
`
`One difference between the two claim sets is that the claims of the instant application
`
`broadly recite a buffer system that has a pH of 4 to 8 while the claims of the '938 application
`
`recite that the buffer system comprises histidine and has a pH of 4 to 8. Thus, the claims of the
`
`'938 application are species claims that anticipate the genus claims of the instant application.
`
`This is a provisional nonstatutory double patenting rejection because the patentably
`
`indistinct claims have not in fact been patented.
`
`5.
`
`Claims 1-10, 12-31 are provisionally rejected on the ground of nonstatutory double
`
`patenting as being unpatentable over claims 1-30 of copending Application No. 141147,287.
`
`Although the claims at issue are not identical, they are not patentably distinct from each other
`
`because both sets of claims are directed to a stable liquid aqueous pharmaceutical formulation
`
`comprising a human IgG 1 anti-human tumor necrosis factor alpha (TNFa) antibody or antigen-
`
`binding fragment thereof at a concentration of 20 to 150 mg/ml, a polyol, a surfactant, and a
`
`buffer system having a pH of 4 to 8.
`
`Claim 1 of the instant application recites a stable liquid aqueous pharmaceutical
`
`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
`
`Ex. 2010-0012
`
`

`
`Application/Control Number: 14/091,661
`Art Unit: 1647
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`Page 12
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`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
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`polyol, (c) a surfactant, and (d) a buffer system having a pH of 4 to 8, wherein the antibody
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`comprises a light chain variable region comprising the light chain complementarity determining
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`region (CDR)l, CDR2, and CDR3 of D2E7; and a heavy chain variable region comprising the
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`heavy chain CDRl, CDR2, and CDR3 ofD2E7. Claims 8, 19, 20, 27, and 31 recite that the
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`polyol is mannitol. Claims 10 and 31 recite that the polyol is trehalose.
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`Claim 1 of the '287 application recites a stable liquid aqueous pharmaceutical
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`formulation comprising (a) a human IgG 1 anti-human tumor necrosis factor alpha (TNFa)
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`antibody, or an antigen-binding fragment thereof, at a concentration of 20 to 150 mg/ml, (b) a
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`polyol, (c) a surfactant, and (d) a buffer system comprising succinate and having a pH of 4 to 8,
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`wherein the antibody comprises a light chain variable region comprising the light chain
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`complementarity determining region (CDR)1, CDR2, and CDR3 of D2E7; and a heavy chain
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`variable region comprising the heavy chain CDR1, CDR2, and CDR3 of D2E7. Claim 8 recites
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`that the polyol is mannitol. Claims 11, 19-21, and 27 recite that the polyol is trehalose.
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`The pH of the buffer system/formulation and the concentrations of the antibody, polyol,
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`and polysorbate 80 are the same in both claim sets. The human IgG 1 anti-human tumor necrosis
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`factor alpha (TNFa) antibody or antigen-binding fragment thereof is also identical in both the
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`instant application and the '938 application.
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`One difference between the two claim sets is that the claims of the instant application
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`broadly recite a buffer system that has a pH of 4 to 8 while the claims of the '938 application
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`recite that the buffer system comprises succinate and has a pH of 4 to 8. Thus, the claims of the
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`'938 application are species claims that anticipate the genus claims of the instant application.
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`Ex. 2010-0013
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`

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`Application/Control Number: 14/091,661
`Art Unit: 1647
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`Page 13
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`This is a provisional nonstatutory double patenting rejection because the patentably
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`indistinct claims have not in fact been patented.
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`Claim Rejections- 35 USC§ 103
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`The following is a quotation of pre-AlA 35 U.S.C. 103(a) which forms the basis for all
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`obviousness rejections set forth in this Office action:
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`(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.
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`In the event the determination of the status of the application as subject to AlA 35 U.S.C.
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`102 and 103 (or as subject to pre-AlA 35 U.S.C. 102 and 103) is incorrect, any correction of the
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`statutory basis for the rejection will not be considered a new ground of rejection if the prior art
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`relied upon, and the rationale supporting the rejection, would be the same under either status.
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`This application currently names joint inventors. In considering patentability of the
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`claims under pre-AlA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the
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`various claims was commonly owned at the time any inventions covered therein were made
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`absent any evidence to the contrary. Applicant is advised of the obligation under 37 CPR 1.56 to
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`point out the inventor and invention dates of each claim that was not commonly owned at the
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`time a later invention was made in order for the examiner to consider the applicability of pre-
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`AlA 35 U.S.C. 103(c) and potential pre-AlA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AlA
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`35 U.S.C. 103(a).
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`Ex. 2010-0014
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`

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`Application/Control Number: 14/091,661
`Art Unit: 1647
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`Page 14
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`6.
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`Claims 1-10, 12, 13, and 16-18 are rejected under pre-AlA 35 U.S.C. 103(a) as being
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`unpatentable over Gombotz et al. (US 20030180287) and Salfeld et al. (U.S. Patent 6,090,382).
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`Gombotz et al. teach an aqueous pharmaceutical composition comprising an antibody or
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`an Fe domain containing polypeptide, a buffer, tonicity modifier, and one or more excipients
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`(page 1, [0006]; page 3, [0035-0036]; pages 4-5, [0052]). Gombotz et al. teaches that the
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`composition may contain an antibody that recognizes tumor necrosis factor (TNF) (page 3,
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`[0036]). Gombotz et al. disclose that the buffer maintains the composition pH at a range of
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`about 6.0 and about 7.0 (page 1, [0006]; page 4, [0046]). Gombotz et al. teach that buffering
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`agents include potassium phosphate and sodium or potassium citrate and that the concentration
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`of the buffer is between about 1mM to about 1M (page 4, [0045]). Gombotz et al. disclose that a
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`tonicity modifier includes mannitol (page 4, top of column 2, [0047]). Gombotz et al. teach that
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`the concentration of the tonicity modifier is between about 1 mM to 1M (page 4, top of column
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`2, [0045]). Additionally, Gombotz et al. indicate that a suitable excipients to stabilize the
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`polypeptide while in solution include, Tween-80 (also known in the art as polysorbate 80),
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`mannitol, and trehalose (page 4, [0048]). Gombotz et al. indicate the concentration of one or
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`more excipients is between about 0.001 to 5 percent weight percent (page 4, [0049]). Gombotz
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`et al. teach that the formulation can comprise about 10 to about 100 mg/ml of the polypeptide
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`(page 4, [0051]; page 8, claim 1).
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`Gombotz et al. does not disclose an aqueous pharmaceutical composition comprising an
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`antibody that comprises the light chain variable region CDRs and the heavy chain variable region
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`CDRs of the antibody, D2E7.
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`Ex. 2010-0015
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`

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`Application/Control Number: 14/091,661
`Art Unit: 1647
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`Page 15
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`Salfeld et al. teaches TNFa is implicated in the pathophysiology of a variety of human
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`diseases, such as shock, sepsis, infections, autoimmune diseases, transplant rejection and graft-
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`versus-host disease (column 1, lines 10-20). Salfeld discloses that therapeutic strategies have
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`been designed to inhibit or counteract hTNFa activity, in particular antibodies that bind to and
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`neutralize hTNFa (column 1, lines 23-27). Salfeld et al. teach a recombinant anti-hTNFa
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`antibody, termed D2E7, neutralizes hTNFa activity (column 2, lines 50-67; column 9, lines 43-
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`67 through column 5). Salfeld et al. disclose administering an anti-hTNFa to a human subject
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`suffering from a disorder in which TNFa activity is detrimental such that human TNFa activity
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`in the human subject is inhibited (column 4, lines 32-48; columns 24-27).
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`It would have been obvious to the person of ordinary skill in the art at the time the
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`invention was made to modify the aqueous pharmaceutical composition as taught by Gombotz et
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`al. by substituting the antibody or an Fe domain containing polypeptide with the anti-hTNFa
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`antibody, D2E7, as taught by Salfeld et al. The person of ordinary skill in the art would have
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`been motivated to make that modification to provide a stable liquid formulation that allows long
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`term storage of the antibody, as well as for convenience of use for the patients, as the
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`formulation does not require any extra steps, such as rehydrating (see for example, Gombotz et
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`al., page 1, [0005], [0023]). The person of ordinary skill in the art reasonably would have
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`expected success because similar preparations were already being generated at the time the
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`invention was made and the substitution of one known TNF antibody for another would have
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`yielded predictable results to one of ordinary skill in the art at the time of the invention (see KSR
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`International Co. v. Teleflex, Inc