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 .
DETAILED ACTION
Claims 65-72 and 74-82 are pending.
Claims 73, 83, and 84 are canceled.
Claims 65-67, 70, 72, 74-76, 79, 81, and 82 are currently amended.
Claims 65-72 and 74-82 are under examination on the merits.
Rejections Withdrawn
35 U.S.C. 112(b)
The rejection of claims 65-82 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inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, has been withdrawn. Claims 65 and 75 have been amended to remove the recitation of “optional.” Claim 73 has been canceled.
35 U.S.C. 112(a)
The rejection of claims 83 and 84 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, has been withdrawn due to the cancellation of the claims.
35 U.S.C. 102(a)(1)
The rejection of claim(s) 65-72 and 74-84 under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (WO 2018/226580, international publication date: 12/13/2018, in IDS from 07/21/2023), is withdrawn in view of the claim amendments, dated 12/17/2025.
Nonstatutory Double Patenting
The provisional rejection of claims 65-72 and 74-84 on the ground of nonstatutory double patenting as being unpatentable over claim 65 of copending Application No. 18/334,748 in view of Chen et al. (WO 2018/226580, international publication date: 12/13/2018, in IDS from 07/21/2023), is withdrawn in view of the claim amendments, dated 12/17/2025.
The provisional rejection of claims 65-72 and 74-84 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/819,116 in view of Chen et al. (WO 2018/226580, international publication date: 12/12/2018, in IDS from 07/21/2023), is withdrawn in view of the claim amendments, dated 12/17/2025.
New Grounds of Rejection – Necessitated by Amendment
35 U.S.C. 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 65-72 and 74-82 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (WO 2018/226580, international publication date: 12/13/2018, in IDS from 07/21/2023) in view of Van Den Brink et al. (WO 2009/083009, international publication date: 07/09/2009).
At p. 18 and 19, Chen et al. teach that “[p]rovided herein are antibodies that specifically bind PD-1 or antigen binding fragments thereof, polynucleotides encoding the antibodies provided herein, vectors, host cells and methods of making and using the antibodies. The antibodies or antigen binding fragments thereof may be agonistic antibodies… Some cancer patients treated with immune checkpoint inhibitors including PD-1 antagonists, develop autoimmune-related adverse events, such as symptoms of arthritis, colitis, or psoriasis. One hypothesis to explain this observation is that self-reactive T cells in these patients were being actively suppressed through PD-1, and were ‘unleashed’ in the presence of a PD-1 antagonist. It is then reasonable to reverse this hypothesis and believe that is it likely that "already-unleashed" T cells in patients who have autoimmune disease could be suppressed through PD-1 ligation/agonism… SNPs in the PD-1 gene PDCD1 have been found to be associated with a variety of autoimmune diseases including rheumatoid arthritis, lupus, and ankylosing spondylitis (summarized by Zamani et al., Cell Immunol 2016 310:27-41). Though functions have not yet been elucidated for the PD-1 SNPs, these associations may indicate that a reduction in PD-1 activity may lead to a reduction in T cell suppression, which could increase susceptibility to autoimmune disease. There is a need for therapeutics to suppress autoreactive T cells in autoimmune diseases. PD-1+ T cells have been found in tissues from patients with autoimmune diseases, including rheumatoid arthritis and Sjogren’s Syndrome (Wan et al, J Immunol 2006 177(12):8844-50.; Kobayashi et al., J Rheumatol 2005 32(11):2156-63). An antibody capable of agonizing PD-1 could be used to suppress T cell proliferation and cytokine release, to limit damage within tissues and restore immune homeostasis. A PD-1 agonist mAb would target activated instead of resting naive and memory T cells and B cells. In this way the therapeutic would suppress immune responses towards self-antigens in patients with autoimmune diseases without compromising immune memory responses to pathogens (emphasis added).”
At p. 51, Chen et al. teach that “[i]n some embodiments, the antibody that specifically binds PD-1 or the antigen binding fragment thereof comprises at least one mutation in the Fc region that enhances binding of the antibody to FcγRIIb. Enhanced binding to FcγRIIb may result in attenuation of FcγRIIb+ B cells, and/or result in clustering of the antibody and subsequent activation of PD-1 downstream signaling pathways… In some embodiments, the antibody that specifically binds PD-1 or the antigen binding fragment thereof comprises a P238D mutation.”
As such Chen et al. teach a method of treating an autoimmune disease, such as rheumatoid arthritis, comprising administering to a patient in need thereof an agonist anti-PD-1 antibody comprising an Fc region mutation, such as a P238D mutation, that provides enhanced binding to FcγRIIb. The method of Chen et al. would be expected to suppress autoreactive T cells in autoimmune disease. Chen et al. do not teach or suggest a method of inhibiting an activated immune T cell and the activity of a B cell (or treating an autoimmune disorder), the method comprising administering a polypeptide to the subject in need thereof, wherein the polypeptide comprises: a) an inhibitory receptor effector domain (agonist anti-PD-1 antibody), b) an Fc region that selectively bind to FcγRIIb, such as an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, and c) an antibody that binds to FcγRIIb. These deficiencies are remedied by Van Den Brink et al.
At claim 51, Van Den Brink et al. teach a bispecific molecule that comprises an anti-CD32b (also known as FcγRIIb) antibody and a second binding specificity for a human effector cell. At p. 12, it is stated that “[a]s used herein, the term ‘effector cell’ refers to an immune cell which is involved in the effector phase of an immune response, as opposed to the cognitive and activation phases of an immune response. Exemplary immune cells include a cell of a myeloid or lymphoid origin, for instance lymphocytes (such as B cells and T cells including cytolytic T cells (CTLs))…” At p. 51, Van Der Brink et al. teach that “the anti-CD32b antibody of the invention may be used in the treatment of inflammatory and/or autoimmune diseases.”
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Chen et al. with those of Van Der Brink et al. to develop a method of inhibiting an activated immune T cell and the activity of a B cell (or treating an autoimmune disorder), the method comprising administering a polypeptide to the subject in need thereof, wherein the polypeptide comprises: a) an inhibitory receptor effector domain (agonist anti-PD-1 antibody), b) an Fc region that selectively bind to FcγRIIb, such as an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, and c) an antibody that binds to FcγRIIb. One of ordinary skill in the art would have been motivated to do so, because Chen et al. teach a method of treating an autoimmune disease, comprising administering to a patient in need thereof an agonist anti-PD-1 antibody comprising an Fc region mutation, such as a P238D mutation, that provides enhanced binding to FcγRIIb. The method of Chen et al. would be expected to suppress autoreactive T cells in autoimmune disease. Furthermore Van Den Brink et al. teach a bispecific molecule that comprises an anti-FcγRIIb antibody and a second binding specificity for a human effector cell, and Van Der Brink et al. teach that “the anti-CD32b antibody of the invention may be used in the treatment of inflammatory and/or autoimmune diseases.” In view of these teachings, one of ordinary skill in the art would have been motivated to prepare a bispecific antibody that comprises an anti-FcγRIIb antibody and a second binding specificity for a human effector cell (anti-PD-1 antibody), wherein said bispecific antibody comprises an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, because there would have been a reasonable expectation that the resultant bispecific antibody is effective in treating autoimmune diseases, such as such as rheumatoid arthritis.
The invention of Chen et al. and Van Den Brink et al. meets the limitations of claims 65-67, 69-72, 75-77, and 79-81.
With respect to claims 68 and 78, PDCD1 is the gene that encodes PD-1.
With respect to claims 74 and 82, the invention of Chen et al. and Van Den Brink et al. comprises an antigen-binding region and an Fc domain, and one of ordinary skill in the art would recognize that said invention could bind T cells and Fc receptors on immune cells at the same time or nearly the same time.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Nonstatutory 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 65-72 and 74-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 65 of copending Application No. 18/334,748 in view of Chen et al. (WO 2018/226580, international publication date: 12/13/2018, in IDS from 07/21/2023) and Van Den Brink et al. (WO 2009/083009, international publication date: 07/09/2009).
The conflicting claim recites a polypeptide comprising an anti-PD-1 antibody linked to an Fc polypeptide, wherein the anti-PD-1 antibody is a PD-1 agonist and the Fc polypeptide selectively binds to FcγRIIB over FcγRIIA, and wherein the Fc polypeptide comprises P238D and S239D mutations.
The teachings of Chen et al. and Van Den Brink et al. are detailed above. In view of these teachings, one of ordinary skill in the art would have been motivated to modify the conflicting claim to recite a method of inhibiting an activated immune T cell and the activity of a B cell (or treating an autoimmune disorder), the method comprising administering a polypeptide to the subject in need thereof, wherein the polypeptide comprises: a) an inhibitory receptor effector domain (agonist anti-PD-1 antibody), b) an Fc region that selectively bind to FcγRIIb, such as an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, and c) an antibody that binds to FcγRIIb. One of ordinary skill in the art would have been motivated to do so, because Chen et al. teach a method of treating an autoimmune disease, comprising administering to a patient in need thereof an agonist anti-PD-1 antibody comprising an Fc region mutation, such as a P238D mutation, that provides enhanced binding to FcγRIIb. The method of Chen et al. would be expected to suppress autoreactive T cells in autoimmune disease. Furthermore Van Den Brink et al. teach a bispecific molecule that comprises an anti-FcγRIIb antibody and a second binding specificity for a human effector cell, and Van Der Brink et al. teach that “the anti-CD32b antibody of the invention may be used in the treatment of inflammatory and/or autoimmune diseases.” In view of these teachings, one of ordinary skill in the art would have been motivated to prepare a bispecific antibody that comprises an anti-FcγRIIb antibody and a second binding specificity for a human effector cell (such as an anti-PD-1 antibody, as recited in the conflicting claims), wherein said bispecific antibody comprises an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, because there would have been a reasonable expectation that the resultant bispecific antibody is effective in treating autoimmune diseases, such as such as rheumatoid arthritis. The invention of the conflicting claim and Chen et al. meets the limitations of claims 65-67, 69-72, 75-77, and 79-81.
With respect to claims 68 and 78, PDCD1 is the gene that encodes PD-1.
With respect to claims 74 and 82, the invention of Chen et al. comprises an antigen-binding region and an Fc domain, and one of ordinary skill in the art would recognize that said invention could bind T cells and Fc receptors on immune cells at the same time or nearly the same time.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 65-72 and 74-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/819,116 in view of Chen et al. (WO 2018/226580, international publication date: 12/12/2018, in IDS from 07/21/2023).
The conflicting claim recites an agonist anti-PD-1 antibody linked to a CH1-CH2-CH3 domain (Fc region).
The teachings of Chen et al. and Van Den Brink et al. are detailed above. In view of these teachings, one of ordinary skill in the art would have been motivated to modify the conflicting claim to recite a method of inhibiting an activated immune T cell and the activity of a B cell (or treating an autoimmune disorder), the method comprising administering a polypeptide to the subject in need thereof, wherein the polypeptide comprises: a) an inhibitory receptor effector domain (agonist anti-PD-1 antibody), b) an Fc region that selectively bind to FcγRIIb, such as an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, and c) an antibody that binds to FcγRIIb. One of ordinary skill in the art would have been motivated to do so, because Chen et al. teach a method of treating an autoimmune disease, comprising administering to a patient in need thereof an agonist anti-PD-1 antibody comprising an Fc region mutation, such as a P238D mutation, that provides enhanced binding to FcγRIIb. The method of Chen et al. would be expected to suppress autoreactive T cells in autoimmune disease. Furthermore Van Den Brink et al. teach a bispecific molecule that comprises an anti-FcγRIIb antibody and a second binding specificity for a human effector cell, and Van Der Brink et al. teach that “the anti-CD32b antibody of the invention may be used in the treatment of inflammatory and/or autoimmune diseases.” In view of these teachings, one of ordinary skill in the art would have been motivated to prepare a bispecific antibody that comprises an anti-FcγRIIb antibody and a second binding specificity for a human effector cell (such as an anti-PD-1 antibody, as recited in the conflicting claims), wherein said bispecific antibody comprises an Fc region that comprises a P238D mutation, which results in clustering of the antibody, subsequent activation of PD-1 downstream signaling pathways, and autoreactive T cell suppression, because there would have been a reasonable expectation that the resultant bispecific antibody is effective in treating autoimmune diseases, such as such as rheumatoid arthritis. The invention of the conflicting claim and Chen et al. meets the limitations of claims 65-67, 69-72, 75-77, and 79-81.
With respect to claims 68 and 78, PDCD1 is the gene that encodes PD-1.
With respect to claims 74 and 82, the invention of Chen et al. comprises an antigen-binding region and an Fc domain, and one of ordinary skill in the art would recognize that said invention could bind T cells and Fc receptors on immune cells at the same time or nearly the same time.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F 9:00 am - 6:00 pm EST
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on 571-270-3503. 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, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642