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.
`
`14/091,938
`
`11127/2013
`
`Hans-Juergen Krause
`
`110222-0005-304
`
`8062
`
`7590
`118276
`Ropes & Gray, LLP
`1211 Avenue of the Americas
`New York, NY 10036
`
`01/29/2014
`
`EXAMINER
`
`BUNNER, BRIDGET E
`
`ART UNIT
`
`PAPER NUMBER
`
`1647
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`01129/2014
`
`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. 2009-0001
`
`

`
`Application No.
`14/091 ,938
`
`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 7
`
`Ex. 2009-0002
`
`

`
`Application/Control Number: 14/091,938
`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.
`
`Information Disclosure Statement
`
`1.
`
`The information disclosure statement filed 27 November 2013 fails to comply with 37
`
`CPR 1.98(a)(3) because it does not include a concise explanation of the relevance, as it is
`
`presently understood by the individual designated in 37 CPR 1.56(c) most knowledgeable about
`
`the content of the information, of each patent/reference listed that is not in the English language.
`
`It is noted that the Voight reference has been crossed off of the IDS because it is in German and
`
`no translation or concise explanation has been provided.
`
`Claim Rejections- 35 USC§ 103
`
`The following is a quotation of pre-AlA 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.
`
`Ex. 2009-0003
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 3
`
`In the event the determination of the status of the application as subject to AlA 35 U.S.C.
`
`102 and 103 (or as subject to pre-AlA 35 U.S.C. 102 and 103) is incorrect, any correction of the
`
`statutory basis for the rejection will not be considered a new ground of rejection if the prior art
`
`relied upon, and the rationale supporting the rejection, would be the same under either status.
`
`This application currently names joint inventors. In considering patentability of the
`
`claims under pre-AlA 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 CPR 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 pre-
`
`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
`
`35 U.S.C. 103(a).
`
`2.
`
`Claims 1-10, 12, 13, and 16-18 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Gombotz et al. (US 20030180287) and Salfeld et al. (U.S. Patent 6,090,382).
`
`Gombotz et al. teach an aqueous pharmaceutical composition comprising an antibody or
`
`an Fe domain containing polypeptide, a buffer, tonicity modifier, and one or more excipients
`
`(page 1, [0006]; page 3, [0035-0036]; pages 4-5, [0052]). Gombotz et al. teaches that the
`
`composition may contain an antibody that recognizes tumor necrosis factor (TNF) (page 3,
`
`[0036]). Gombotz et al. disclose that the buffer maintains the composition pH at a range of
`
`about 6.0 and about 7.0 (page 1, [0006]; page 4, [0046]). Gombotz et al. teach that a buffering
`
`agent for use in the pharmaceutical composition includes histine and that the concentration of the
`
`Ex. 2009-0004
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 4
`
`buffer is between about lmM to about 1M (page 4, [0045]). Gombotz et al. disclose that a
`
`tonicity modifier includes mannitol (page 4, top of column 2, [0047]). Gombotz et al. teach that
`
`the concentration of the tonicity modifier is between about 1 mM to 1M (page 4, top of column
`
`2, [0045]). Additionally, Gombotz et al. indicate that a suitable excipient to stabilize the
`
`polypeptide while in solution includes, Tween-80 (also known in the art as polysorbate 80),
`
`mannitol, and trehalose (page 4, [0048]). Gombotz et al. indicate the concentration of one or
`
`more excipients is between about 0.001 to 5 percent weight percent (page 4, [0049]). Gombotz
`
`et al. teach that the formulation can comprise about 10 to about 100 mg/ml of the polypeptide
`
`(page 4, [0051]; page 8, claim 1). Gombotz et al. disclose that a kit or container may contain an
`
`aqueous pharmaceutical composition, wherein the concentration of the polypeptide is generally
`
`within the range of from about 0.05 to about 20,000 flg/ml (or about 0.00005 to about 20 mg/ml)
`
`of aqueous formulation (page 6, [0065]). Gombotz et al. state that the pharmaceutical
`
`composition can be administered parenterally (such as subcutaneously) by a bolus injection or
`
`continuous infusion (page 5, [0062]; page 6, [0064]).
`
`Gombotz et al. does not disclose an aqueous pharmaceutical composition comprising an
`
`antibody that comprises the light chain variable region CDRs and the heavy chain variable region
`
`CDRs of the antibody, D2E7.
`
`Salfeld et al. teaches TNFa is implicated in the pathophysiology of a variety of human
`
`diseases, such as shock, sepsis, infections, autoimmune diseases, transplant rejection and graft-
`
`versus-host disease (column 1, lines 10-20). Salfeld discloses that therapeutic strategies have
`
`been designed to inhibit or counteract hTNFa activity, in particular antibodies that bind to and
`
`neutralize hTNFa (column 1, lines 23-27). Salfeld et al. teach a recombinant anti-hTNFa
`
`Ex. 2009-0005
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 5
`
`antibody, termed D2E7, neutralizes hTNFa activity (column 2, lines 50-67; column 9, lines 43-
`
`67 through column 5). Salfeld et al. disclose administering an anti-hTNFa to a human subject
`
`suffering from a disorder in which TNFa activity is detrimental such that human TNFa activity
`
`in the human subject is inhibited (column 4, lines 32-48; columns 24-27).
`
`It would have been obvious to the person of ordinary skill in the art at the time the
`
`invention was made to modify the aqueous pharmaceutical composition as taught by Gombotz et
`
`al. by substituting the antibody or an Fe domain containing polypeptide with the anti-hTNFa
`
`antibody, D2E7, as taught by Salfeld et al. The person of ordinary skill in the art would have
`
`been motivated to make that modification to provide a stable liquid formulation that allows long
`
`term storage of the antibody, as well as for convenience of use for the patients, as the
`
`formulation does not require any extra steps, such as rehydrating (see for example, Gombotz et
`
`al., page 1, [0005], [0023]). The person of ordinary skill in the art reasonably would have
`
`expected success because similar preparations were already being generated at the time the
`
`invention was made and the substitution of one known TNF antibody for another would have
`
`yielded predictable results to one of ordinary skill in the art at the time of the invention (see KSR
`
`International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Therefore, the
`
`claimed invention as a whole was clearly prima facie obvious over the prior art.
`
`3.
`
`Claims 14, 15, and 19-31 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Gombotz et al. (US 20030180287) and Salfeld et al. (U.S. Patent 6,090,382) as
`
`applied to claims 1-10, 12, 13, and 16-18 above.
`
`The teachings of Gombotz et al. and Salfeld et al. are set forth above.
`
`Ex. 2009-0006
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 6
`
`Gombotz et al. and Salfeld et al. do not recite specific amounts (mg/ml) of mannitol and
`
`polysorbate 80 recited in claims 14, 15, and 19-31.
`
`However, it would have been obvious to one having ordinary skill in the art at the time
`
`the invention was made to modify the amounts of buffer, disaccharide/tonicity modifier (i.e.,
`
`mannitol), and surface agent/excipient (i.e., polysorbate 80) utilized in the compositions as
`
`taught by Gombotz et al. and Salfeld et al. The person of ordinary skill in the art would have
`
`been motivated to make that modification to in order to improve upon what is already known,
`
`thus determining the optimum combination amounts of reagents. The person of ordinary skill in
`
`the art reasonably would have expected success because optimization of conditions is routine in
`
`the art. See In re Aller 220 F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) "[W]here the
`
`general conditions of a claim are disclosed in the prior art, it is not inventive to discover the
`
`optimum or workable ranges by routine experimentation". See also In re Hoeschele, 406 F.2d
`
`1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the
`
`broad scope of the references were held to be unpatentable thereover because, among other
`
`reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or
`
`molar proportions.). Therefore, the claimed invention as a whole is clearly prima facie obvious
`
`over the prior art.
`
`4.
`
`Claims 1-10, 12, 13, and 16-18 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Heavner et al. (U.S. Patent 7,250,165) and Salfeld et al. (U.S. Patent
`
`6,090,382).
`
`Ex. 2009-0007
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 7
`
`Heavner et al. teach a stable liquid formulation/solution of a TNF antibody (column 31,
`
`lines 18-64; column 42, lines 54-66; column 43, lines 15-29). Heavner et al. disclose that the
`
`antibody binds human TNFa and can have an IgG 1 isotype (column 23, lines 5-38; column 38,
`
`lines 37-65). Heavner et al. teach that that anti-TNF antibody may be administered in a range
`
`from at least about 0.01 to 500 mg/kg per dose (column 41, lines 26-65; column 42, lines 4-9).
`
`Heavner et al. also teach that the range of the anti-TNF antibody includes amounts yielding upon
`
`reconstitution, concentrations from about 1.0 flg/ml to about 1000 mg/ml, although lower and
`
`higher concentrations are operable and dependent upon the intended delivery vehicle (column
`
`32, lines 3-1 0). Heavner et al. disclose that the formulation may comprise a buffer with a pH of
`
`4 to about pH 10; carbohydrate excipients such as mannitol or trehalose; and non-ionic
`
`surfactants such as polysorbate 80 (column 30, lines 13-62; column 32, lines 28-49). Heavner et
`
`al. indicate that pharmaceutical excipients and additives may be used in the formulation,
`
`including amino acid components such as histidine (column 30, lines 27-40).
`
`Heavner et al. does not disclose an aqueous pharmaceutical composition comprising an
`
`antibody that comprises the light chain variable region CDRs and the heavy chain variable region
`
`CDRs of the antibody, D2E7.
`
`Salfeld et al. teaches TNFa is implicated in the pathophysiology of a variety of human
`
`diseases, such as shock, sepsis, infections, autoimmune diseases, transplant rejection and graft-
`
`versus-host disease (column 1, lines 10-20). Salfeld discloses that therapeutic strategies have
`
`been designed to inhibit or counteract hTNFa activity, in particular antibodies that bind to and
`
`neutralize hTNFa (column 1, lines 23-27). Salfeld et al. teach a recombinant anti-hTNFa
`
`antibody, termed D2E7, neutralizes hTNFa activity (column 2, lines 50-67; column 9, lines 43-
`
`Ex. 2009-0008
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 8
`
`67 through column 5). Salfeld et al. disclose administering an anti-hTNFa to a human subject
`
`suffering from a disorder in which TNFa activity is detrimental such that human TNFa activity
`
`in the human subject is inhibited (column 4, lines 32-48; columns 24-27).
`
`It would have been obvious to the person of ordinary skill in the art at the time the
`
`invention was made to modify the aqueous pharmaceutical composition as taught by Heavner et
`
`al. by substituting the Heavner et al. antibody with the anti-hTNFa antibody, D2E7, as taught by
`
`Salfeld et al. The person of ordinary skill in the art would have been motivated to make that
`
`modification to provide a stable liquid formulation of anti-TNFa for administration to subjects
`
`suffering from a disorder in which TNFa activity is detrimental (see for example, Heavner et al,
`
`column 31, lines 18-24;; Salfeld et al. column 4, lines 32-48; columns 24-27). The person of
`
`ordinary skill in the art reasonably would have expected success because similar preparations
`
`were already being generated at the time the invention was made and the substitution of one
`
`known TNF antibody for another would have yielded predictable results to one of ordinary skill
`
`in the art at the time of the invention (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398,
`
`82 USPQ2d 1385 (2007)). Therefore, the claimed invention as a whole was clearly prima facie
`
`obvious over the prior art.
`
`5.
`
`Claims 14, 15, and 19-31 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Heavner et al. (U.S. Patent 7,250,165) and Salfeld et al. (U.S. Patent
`
`6,090,382) as applied to claims 1-10, 12, 13, and 16-18 above.
`
`The teachings of Heavner et al. and Salfeld et al. are set forth above.
`
`Ex. 2009-0009
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 9
`
`Heavner et al. and Salfeld et al. do not recite specific amounts (mg/ml) of mannitol and
`
`polysorbate 80 recited in claims 14, 15, and 19-31.
`
`However, it would have been obvious to one having ordinary skill in the art at the time
`
`the invention was made to modify the amounts of carbohydrate excipient (i.e., mannitol) and
`
`non-ionic surfactant (i.e., polysorbate 80) utilized in the compositions as taught by Heavner et al.
`
`and Salfeld et al. The person of ordinary skill in the art would have been motivated to make that
`
`modification to in order to improve upon what is already known, thus determining the optimum
`
`combination amounts of reagents. The person of ordinary skill in the art reasonably would have
`
`expected success because optimization of conditions is routine in the art. See In re Aller 220
`
`F.2d 454,456, 105 USPQ 233,235 (CCPA 1955) "[W]here the general conditions of a claim are
`
`disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by
`
`routine experimentation". See also In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA
`
`1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references
`
`were held to be unpatentable thereover because, among other reasons, there was no evidence of
`
`the criticality of the claimed ranges of molecular weight or molar proportions.). Therefore, the
`
`claimed invention as a whole is clearly prima facie obvious over the prior art.
`
`Ex. 2009-0010
`
`

`
`Application/Control Number: 14/091,938
`Art Unit: 1647
`
`Page 10
`
`No claims are allowable.
`
`Conclusion
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Bridget E. Bunner whose telephone number is (571)272-0881.
`
`The examiner can normally be reached on 9:00-5:30 M-F.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Joanne Hama can be reached on (571) 272-2911. The fax phone number for the
`
`organization where this application or proceeding is assigned is 571-273-8300.
`
`Information regarding the status of an application may be obtained from the Patent
`
`Application Information Retrieval (PAIR) system. Status information for published applications
`
`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
`
`applications is available through Private PAIR only. For more information about the PAIR
`
`system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
`
`system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would
`
`like assistance from a USPTO Customer Service Representative or access to the automated
`
`information system, call800-786-9199 (IN USA OR CANADA) or 571-272-1000.
`
`BEB
`Art Unit 1647
`21 January 2014
`
`/Bridget E Bunner/
`Primary Examiner, Art Unit 1647
`
`Ex. 2009-0011