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.
`
`141147,287
`
`01103/2014
`
`Hans-Juergen Krause
`
`110222-0005-306
`
`2290
`
`118276
`7590
`Ropes & Gray, LLP
`1211 Avenue of the Americas
`New York, NY 10036
`
`02/07/2014
`
`EXAMINER
`
`BUNNER, BRIDGET E
`
`ART UNIT
`
`PAPER NUMBER
`
`1647
`
`NOTIFICATION DATE
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`DELIVERY MODE
`
`02/07/2014
`
`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. 2038-0001
`
`

`
`Application No.
`14/147,287
`
`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) 1-30 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) 1-30 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 113114· 1124114.
`
`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 20t40203
`
`Ex. 2038-0002
`
`

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`Application/Control Number: 141147,287
`Art Unit: 1647
`
`Page 2
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`DETAILED ACTION
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`The present application is being examined under the pre-AlA first to invent provisions.
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`Status of Application, Amendments and/or Claims
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`Claims 1-30 are under consideration in the instant application.
`
`Information Disclosure Statement
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`1.
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`The information disclosure statements filed 03 January 2014 and 24 January 2014 fail to
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`comply with 37 CPR 1.98(a)(3) because they do not include a concise explanation of the
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`relevance, as it is presently understood by the individual designated in 37 CPR 1.56(c) most
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`knowledgeable about the content of the information, of each patent/reference listed that is not in
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`the English language. The Voigt reference has been crossed off of the IDS of 03 January 2014
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`because it is in German and no translation or concise explanation had been provided. It is noted
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`that a translation of this reference was submitted with the IDS of 24 January 2014. Thus, the
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`Voigt reference cited on the IDS of 24 January 2014 was considered. The EP-0453898 and
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`Fiedler references cited on the IDS of 24 January 2014 were not considered because these
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`references were not in English and no translation or concise explanation was provided. The
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`Salfeld abstract cited on the IDS of 24 January 2014 was not considered because it was blurry
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`and illegible.
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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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`Ex. 2038-0003
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`

`
`Application/Control Number: 141147,287
`Art Unit: 1647
`
`Page 3
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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).
`
`2.
`
`Claims 1-13 and 16-18 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Lam et al. (U.S. Patent 6,171,586) and Salfeld et al. (U.S. Patent 6,090,382).
`
`Lam et al. teach a stable aqueous pharmaceutical formulation comprising an antibody not
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`subjected to prior lyophilization, a buffer maintaining the pH in a range from about 4.5 to about
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`6.0, a surfactant, and a polyol (abstract; column 2, lines 25-33). Lam et al. disclose that the
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`amount of antibody present in the formulation is, for example, from about 0.1 mg/ml to about 50
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`mg/ml (column 22, lines 1-17). Lam et al. state that buffers that control the pH within the
`
`Ex. 2038-0004
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`

`
`Application/Control Number: 141147,287
`Art Unit: 1647
`
`Page 4
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`desired range include succinate (column 22, lines 18-24; column 6, lines 61-67 through column
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`7, lines 1-2). Lam et al. teach that the buffer concentration can be from about lmM to about 50
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`mM (column 22, lines 25-30). Lam et al. disclose that the polyol is a substance with multiple
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`hydroxyl groups and includes sugars (such as the nonreducing sugar, trehalose), sugar alcohols
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`(such as mannitol), and sugar acids (column 6, lines 38-52; column 22, lines 31-48). Lam et al.
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`disclose that the polyol may be in the range from about 1% to about 15% w/v (column 22, lines
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`31-48). Lam et al. teach that the surfactant in the formulation may be polysorbate 80 and may be
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`present in an amount from about 0.001% to about 0.5% (column 22, lines 49-59). Lam et al. also
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`state that the antibody in the formulation is directed against an antigen of interest, wherein the
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`antigen is TNFa (column 9, lines 59-67 through column 10, lines 1-19). Lam et al. mention that
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`the formulation may be administered subcutaneously at one time or over a series of treatments
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`(column 23, lines 32-54).
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`Lam 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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`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-
`
`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. teach that the antibody is of the IgGl subclass (column 30,
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`Ex. 2038-0005
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`

`
`Application/Control Number: 141147,287
`Art Unit: 1647
`
`Page 5
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`lines 39-47; column 34, lines 44-56; column 2, lines 56-57). Salfeld et al. disclose administering
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`an anti-hTNFa to a human subject suffering from a disorder in which TNFa activity is
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`detrimental such that human TNFa activity in the human subject is inhibited (column 4, lines 32-
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`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 Lam et al.
`
`by substituting the antibody with the anti-hTNFa antibody, D2E7, as taught by Salfeld et al. The
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`person of ordinary skill in the art would have been motivated to make that modification to
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`provide a stable liquid formulation of anti-TNFa that remains biologically active for
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`administration to subjects suffering from a disorder in which TNFa activity is detrimental (see
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`for example, Lam et al., column 1, lines 14-26; column 2, lines 25-33;; Salfeld et al. column 4,
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`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
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`invention was made. Therefore, the claimed invention as a whole was clearly prima facie
`
`obvious over the prior art.
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`3.
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`Claims 14, 15, and 19-30 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Lam et al. (U.S. Patent 6,171,586) and Salfeld et al. (U.S. Patent 6,090,382) as
`
`applied to claims 1-13 and 16-18 above.
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`The teachings of Lam et al. and Salfeld et al. are set forth above.
`
`Lam et al. and Salfeld et al. do not recite specific amounts (mg/ml) of polysorbate 80
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`recited in claims 14, 15, and 19-30.
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`Ex. 2038-0006
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`

`
`Application/Control Number: 141147,287
`Art Unit: 1647
`
`Page 6
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`However, it would have been obvious to one having ordinary skill in the art at the time
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`the invention was made to modify the amounts of surfactant (i.e., polysorbate 80) utilized in the
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`compositions as taught by Lam 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
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`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
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`1955) "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive
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`to discover the optimum or workable ranges by routine experimentation". See also In re
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`Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes
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`which fell within the broad scope of the references were held to be unpatentable thereover
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`because, among other reasons, there was no evidence of the criticality of the claimed ranges of
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`molecular weight or molar proportions.). Therefore, the claimed invention as a whole is clearly
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`prima facie obvious over the prior art.
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`Ex. 2038-0007
`
`

`
`Application/Control Number: 141147,287
`Art Unit: 1647
`
`No claims are allowable.
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`Conclusion
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`Page 7
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to Bridget E. Bunner whose telephone number is (571)272-0881.
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`The examiner can normally be reached on 9:00-5:30 M-F.
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
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`supervisor, Joanne Hama can be reached on (571) 272-2911. The fax phone number for the
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`organization where this application or proceeding is assigned is 571-273-8300.
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`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
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`information system, call800-786-9199 (IN USA OR CANADA) or 571-272-1000.
`
`BEB
`Art Unit 1647
`03 February 2014
`
`/Bridget E Bunner/
`Primary Examiner, Art Unit 1647
`
`Ex. 2038-0008