DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The prior art of record does not disclose an antibody that binds human TNFα having a VH and a VL with the CDRs recited in instant claim 1. Dependent claims 2-3, 18, 20, 38, 40, 42-47, 54, 56, and 58 are free of the prior art. The CDRs of SEQ ID NOS: 1-6 correspond to antibody Ab1 in Table 1. See claim 1. The VH/VL of SEQ ID NOS: 7/8 (see claim 2) and HC/LC of SEQ ID NOS: 9/10 (see claim 3) correspond to antibody Ab1 in Table 2.
The prior art of record does not disclose antibodies that bind human TNFα having a VH and a VL with the CDRs recite in claim 4, parts (a)-(d). Dependent claims 5-17, 19, 21, 39, 41, 48-53, 55, 57, and 59 are free of the prior art.
The CDRs of SEQ ID NOS: 22, 23, 13, 4, 5, and 6 correspond to antibody Ab3 in Table 1. See claim 4, part (a), and claim 5. The VH/VL of SEQ ID NOS: 24/8 (see claim 10) and HC/LC of SEQ ID NOS: 25/10 (see claim 11) correspond to antibody Ab3 in Table 2.
The CDRs of SEQ ID NOS: 22, 23, 13, 14, 5, and 6 correspond to antibody Ab5 in Table 1. See claim 4, part (a), and claim 6. The VH/VL of SEQ ID NOS: 24/27 (see claim 10) and HC/LC of SEQ ID NOS: 25/28 (see claim 11) correspond to antibody Ab5 in Table 2.
The CDRs of SEQ ID NOS: 22, 23, 13, 46, 5, and 6 correspond to antibodies Ab3 and Ab5 in Table 1. See claim 4, part (a), and claim 8. SEQ ID NO: 46 (QASQGIXNYLN) has serine or arginine for the X at amino acid position 7. The serine embodiment corresponds to SEQ ID NO: 4 (for Ab3) and the arginine embodiment corresponds to SEQ ID NO: 14 (for Ab5).
The CDRs of SEQ ID NOS: 22, 23, 13, 14, 5, and 15 correspond to antibody Ab4 in Table 1. See claim 4, part (b), and claim 7. The VH/VL of SEQ ID NOS: 24/17 (see claim 10) and HC/LC of SEQ ID NOS: 25/19 (see claim 11) correspond to antibody Ab4 in Table 2.
The CDRs of SEQ ID NOS: 22, 23, 13, 14, 5, and 47 correspond to antibody Ab4 and Ab5 in Table 1. See claim 4, part (b), and claim 9. SEQ ID NO: 47 (QQYDXLPLT) has asparagine or lysine for the X at amino acid position 5. The asparagine embodiment corresponds to SEQ ID NO: 15 (for Ab4) and the lysine embodiment corresponds to SEQ ID NO: 6 (for Ab5).
The CDRs of SEQ ID NOS: 1, 2, 30, 31, 5, and 32 correspond to antibody Ab6 in Table 1. See claim 4, part (c), and claim 12. The VH/VL of SEQ ID NOS: 33/34 (see claim 13) and HC/LC of SEQ ID NOS: 35/36 (see claim 14) correspond to antibody Ab6 in Table 2.
The CDRs of SEQ ID NOS: 1, 2, 13, 14, 5, and 15 correspond to antibody Ab2 in Table 1. See claim 4, part (d), and claim 15. The VH/VL of SEQ ID NOS: 16/17 (see claim 16) and HC/LC of SEQ ID NOS: 18/19 (see claim 17) correspond to antibody Ab6 in Table 2.
The prior art of record does not disclose nucleic acids encoding the VH of SEQ ID NOS: 9, 18, 25, and 35 or the VL of SEQ ID NOS: 10, 19, 28, and 36 in claim 22. Dependent claims 23-28, 32, 34-35, are free of the prior art.
The prior art of record does not disclose the compositions of claim 29. Dependent claims 30-33 are free of the prior art.
Specification
The disclosure is objected to because of the following informalities: The incorporation of sequence listing paragraph on page 1 of the specification should reference the size of the file in bytes not kilobytes (KB). See MPEP 2422.03(I).
Appropriate correction is required.
Claim Objections
Claim 32 is objected to because of the following informalities: The claim has a period (“.”) following “or” in the body of the claim. Appropriate correction is required.
Claim 36 is objected to because of the following informalities: The claim contains a grammatical error “of Claims 34” where plural “claims” should be the singular “claim.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 36 and 37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 36 is directed to a process of producing an antibody by culturing the cell of claim 34. The cell of claim 34 comprises the vector of claim 23 which in turn comprises the nucleic acid of claim 22. SEQ ID NOS: 9, 18, 25, and 35 are heavy chains and SEQ ID NOS: 10, 19, 28, and 36 are light chains. Claim 22 is directed to only one sequence being encoded. That is, an antibody requires both the heavy and light chains. The method of claim 36 would only produce either a heavy chain or a light chain but not both. The method would not produce an antibody with antigen binding properties. The method of claim 36 is not enabled, and as no antibody is produced by this method, the antibody of claim 37 is not enabled.
Claims 24 and 29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the pairs SEQ ID NO: 9 and 10 (Ab1) , SEQ ID NOS: 18 and 19 (Ab2), SEQ ID NOS: 25 and 28 (Ab5), and SEQ ID NOS: 35 and 36 (Ab6), does not reasonably provide enablement for all pairings encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
SEQ ID NOS: 9, 18, 25, and 35 are heavy chains and SEQ ID NOS: 10, 19, 28, and 36 are light chains. The claims encompass pairing a heavy chain from one antibody with the light chain of a different antibody. For example, claims 24 and 29 encompass pairs such as HC/LC of SEQ ID NOS: 9/19 and 35/10. Pairing a VH from one antibody with a VL from a different antibody would be unpredictable as to whether or not the resulting antibody would have antigen binding. See at least abstract and discussion of Herold et al. with respect to VH/VL association and antigen binding. While the specification discloses and demonstrated antigen binding for the sequence pairs of SEQ ID NO: 9 and 10 (Ab1) , SEQ ID NOS: 18 and 19 (Ab2), SEQ ID NOS: 25 and 28 (Ab5), and SEQ ID NOS: 35 and 36 (Ab6), the scope of the claims is not enabled.
Claims 42-53 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods as discussed below, does not reasonably provide enablement for all methods embraced by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Claims 42 and 45 are directed to methods of treatment by administering a therapeutically effective amount of an antibody.
The term “therapeutically effective amount” as defined in the specification means, as an amount of antibody that will elicit the desired biological or medical response of a subject, for example, reduction or inhibition of a protein activity, or ameliorate symptoms, alleviate conditions, slow or delay disease progression, or prevent a disease, etc.
The term “treatment” or “treating” as defined in the specification refers to all processes wherein there may be a slowing, controlling, delaying or stopping of the progression of the disorders or disease disclosed herein, or ameliorating disorder or disease symptoms, but does not necessarily indicate a total elimination of all disorder or disease symptoms.
The methods do not require any particular therapeutic effect and so all therapeutic effects encompassed by “treatment” and “therapeutically effective amounts” must be enabled. To the degree that the claimed methods encompass cure or prevention(i.e. delaying or stopping of the progression), the claims are not enabled. At least for example, there are no known cures or ways to prevent rheumatoid arthritis or Crohn’s disease (see at least claims 44 and 50). With respect to ameliorating all disorder or disease symptoms, there is no evidence of record nor reason to believe that administering any of the claimed antibodies will reverse joint damage that has occurred in rheumatoid arthritis. At least for example, there is no evidence of record nor reason to believe that administering any of the claimed antibodies will reverse fistulas caused by Crohn’s disease. As set forth in the specification, administration of anti-TNFα antibodies are known to reduce inflammation. However, the specification does not enable all aspects of treatment, including prevention and cure, for all diseases (and all of their symptoms or characteristics) encompassed by the claims.
With respect to claims 47 and 53, only antibody Ab6 was shown to have low to no binding to anti-drug antibodies against Adalimumab See Figures 1-2 and pages 24 and 33-34. Note that claim 1 (upon which claim 47 depends) is directed to antibody Ab1 alone, and thus, claim 47 is not enabled. The method of claim 53 is not enabled for the other antibodies of claim 4.
The scope of the claims is not enabled.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 54-59 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 54-55 require that the antibody be neutralizing. Note that Table 10 indicates that antibodies Ab1-Ab5 inhibit but none of the antibodies completely inactivate human TNFα. It does not appear that antibody Ab6 was tested. See definition of “neutralize” in the specification. It is unclear if the claims 54-55 are properly dependent. Clarification is requested.
Claims 56-57 require that the antibody is an internalizing antibody. It is unclear what this means. It is unclear if internalization of membrane bound TNFα bodies are intended (see Example 3 and Table 4 which only tested antibodies Ab1-Ab4) or if dendritic cell (DC) internalization (see Example 5 which only tested antibodies Ab1-Ab5) or something else was intended. The metes and bounds of the claim cannot be determined.
Claims 58 and 59 require that the antibody has low immunogenicity. The term “low” in claims 58-59 is a relative term which renders the claim indefinite. The term “low” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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 conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-19 and 38-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of copending Application No. 18/312,653 (9/8/2023 claim set). Although the claims at issue are not identical, they are not patentably distinct from each other.
The sequence identifiers in the co-pending and instant claims correspond to the same sequences.
Co-pending claim 1 is directed to antibody conjugates for antibodies with CDRs as recited in instant claims 1 and 4. See conjugates of instant claims 38-39. Co-pending claims 10 have antibodies corresponding to instant claims 1-3. Co-pending claims 13-28 have antibodies as recited in instant claims 5-17. Co-pending claim 28 has cysteines as in instant claims 18-19. Co-pending claim 31 is directed to a pharmaceutical composition as in instant claims 41-42. Co-pending claims 32-35 are directed to methods of treating autoimmune disease or an inflammatory disease in a subject as in instant claims 42-46 and 48-53. Antibodies of the co-pending claims would inherently possess the properties recited in co-pending claims 47 and 53-59. The antibody conjugates of the co-pending claims would have placed the antibodies in the hands of one of ordinary skill in the art. The compositions and method claims do not preclude conjugates.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 20-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/312,653 in view of Bacica et al. (WO 2018/232088, of record).
The co-pending claims are as described above. They are not directed to human IgG1 isotypes as in instant claims 20-21. They are not directed to nucleic acids, vectors, host cells, recombinant methods of production, and antibodies so produced as in instant claims 22-37.
The antibody conjugates of the co-pending claims would have placed the antibodies in the hands of one of ordinary skill in the art.
Bacica et al. discloses human IgG1 antibodies. See at least page 10, lines 24-27. Recombinant production of antibodies using nucleic acids where each chain is encoded by a single vector or by two separate vectors is disclosed. Mammalian host cells are disclosed. Recovery of the antibody from the culture medium is disclosed. See at least pages 23-24.
It would have been obvious to produce nucleic acids encoding the heavy and light chains of the co-pending antibodies (particularly as human IgG1 isotypes), vectors, and mammalian host cells in order to produce the co-pending antibodies recombinantly as taught by Bacica et al. One would have been motivated to so as recombinant production of antibodies would have been conventional.
This is a provisional nonstatutory double patenting rejection.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO 2023/086871 (published 19 May 2023, filed 10 November 2022) appears to be related to the instant application. The document discloses antibodies Ab1-Ab6 of the instant application. See Tables 1-2 at page 26. It is not prior art against the instant claims.
WO 2023/220549 (published 16 November 2023, filed 05 May 2023) appears to be related to U.S. Application 18/312,653 (filed 5 May 2023). See also U.S. Patent Application Publication 2024/0082414 (published 14 March 2024). The WO 2023/220549 document discloses antibodies Ab1-Ab6 of the instant application. See Table 2a, 2b, and 3 at pages 43-44. The document and U.S. application are not prior art against the instant claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 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 published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Marianne P Allen/Primary Examiner, Art Unit 1647
mpa
Prosecution Insights