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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/21/2026 has been entered.
Claim Status
Claim 17 is amended.
Claims 17-18, 27-29, 33 and 69-71 are pending and under examination.
Rejections Withdrawn
The rejection of claims 17 and 69-71 under 35 U.S.C. 102 as being anticipated by Alt is withdrawn in view of amendments to the claims.
New Grounds of Objection
Claim Objections
Claims 69 and 71 are objected to because of the following informalities:
Claim 69 recites “the CAR further comprises a conservative substitution” without providing a reference sequence for the conservative substitution.
Claim 71 recites a “dual specific antibody” and a “bispecific antibody” which are the same.
Appropriate correction is required.
Rejections Maintained
Claim Rejections - 35 USC § 103
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.
Claims 17-18, 27-29, 33, and 69-71 are rejected under 35 U.S.C. 103 as being unpatentable over Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) in view of Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
The disclosure of Alt is directed to novel anti-PD1 antibody reagents and discloses the generation of the antibodies of the instant invention from the same parent antibody 17D8 (see Abstract, and Alt Table 1).
Regarding claim 17, pertaining to a composition, kit or combination comprising the antibody, antibody reagent, antigen-binding portion thereof, or CAR comprising the disclosed CDRs, Alt discloses the claimed antibodies and administration of the antibodies as a part of combination therapy ([00136], Lines 1-3). Alt discloses the following antibodies of instant claim 17 with corresponding sequences shown below:
Clone Name
Instant
Alt
397-27-25
CDRs SEQ ID NO: 3-8
Heavy chain SEQ ID NO: 1
Light chain SEQ ID NO: 2
Heavy chain SEQ ID NO: 168
Light chain SEQ ID NO: 223
319-9-15
CDRs SEQ ID NO: 19-24
Heavy chain SEQ ID NO: 17
Light chain SEQ ID NO: 18
Heavy chain SEQ ID NO: 95
Light chain SEQ ID NO: 128
319-9-75
CDRs SEQ ID NO: 11-16
Heavy chain SEQ ID NO: 9
Light chain SEQ ID NO: 10
CDRs SEQ ID NO: 71-76
319-9-27
CDRs SEQ ID NO: 27-32
Heavy chain SEQ ID NO: 25
Light chain SEQ ID NO: 26
CDRs SEQ ID NO: 41-46
Heavy chain SEQ ID NO: 7
Light chain SEQ ID NO: 8
397-27-93
CDRs SEQ ID NO: 35-40
Heavy chain SEQ ID NO: 33
Light chain SEQ ID NO: 34
Heavy chain SEQ ID NO: 9
Light chain SEQ ID NO: 10
319-9-34
CDRs SEQ ID NO: 43-48
Heavy chain SEQ ID NO: 41
Light chain SEQ ID NO: 42
CDRs SEQ ID NO: 53-58
Heavy chain SEQ ID NO: 11
Light chain SEQ ID NO: 12
319-9-17
CDRs SEQ ID NO: 51-56
Heavy chain SEQ ID NO: 49
Light chain SEQ ID NO: 50
Heavy chain SEQ ID NO: 3
Light chain SEQ ID NO: 4
319-9-53
CDRs SEQ ID NO: 59-64
Heavy chain SEQ ID NO: 57
Light chain SEQ ID NO: 58
CDRs SEQ ID NO:35-40
Heavy chain SEQ ID NO: 5
Light chain SEQ ID NO: 6
397-27-23
CDRs SEQ ID NO: 67-72
Heavy chain SEQ ID NO: 65
Light chain SEQ ID NO: 66
Heavy chain SEQ ID NO: 13
Light chain SEQ ID NO: 14
397-27-3
CDRs SEQ ID NO: 75-80
Heavy chain SEQ ID NO: 73
Light chain SEQ ID NO: 74
Heavy chain SEQ ID NO: 15
Light chain SEQ ID NO: 16
Regarding 69, wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 17 further comprises a conservative substitution in a sequence not comprised by a CDR, Alt discloses wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of the disclosure further comprises a conservative substitution in a sequence not comprised by a CDR (Pg. 92, claim 13).
Regarding claim 70, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is fully humanized except for the CDR sequences, Alt discloses the antibody, antibody reagent, antigen-binding portion thereof, or CAR of the disclosure is fully humanized except for the CDR sequences (Pg. 92, claims 14 and 15).
Regarding claim 71, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is selected from the list of disclosed group of antibody formats, Alt discloses wherein the antibody is an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody (Pg. 92, claim 16).
The disclosure of Alt does not teach: (1) the composition, kit or combination of the disclosure further comprises an immunosuppressive agent from the list disclosed in claim 17, (2) the immunosuppressive agent is conjugated to the antibody or (3) administration of the anti-PD1 antibody for the treatment of an autoimmune disorder or for suppressing an immune response.
These deficiencies are taught by Shibayama.
The disclosure of Shibayama is directed to anti-PD1 agonists as therapeutic agents for treating autoimmune disease ([0009]-[0010]).
Regarding the limitation of claim 17 wherein the composition, kit or combination further comprises an immunosuppressive agent selected from the disclosed list, Shibayama teaches use of the PD-1 agonist antibody of the disclosure for the treatment of autoimmune diseases such as multiple sclerosis and SLE in combination with autoimmune therapeutics including fingolimod ([0244]-[0245]).
Regarding claim 18, wherein the antibody, antibody reagent, or antigen-binding portion thereof of the composition, kit or combination of claim 17 is conjugated to the immunosuppressive agent, Alt teaches that antibody of the disclosure used in an antibody-drug conjugate (Pg. 17, claim 18) and Shibayama teaches combinatorial administration of the agonist PD-1 antibodies with known autoimmune therapeutics ([0244]-[0245]).
Regarding claims 27-29 and 33, pertaining to a method of treating an autoimmune disorder, wherein the autoimmune disorder is a T cell-mediated disorder selected from the group disclosed in claim 29 (claim 27-29) and a method of suppressing an immune response in a subject (claim 33) comprising administration of an antibody of the disclosure, Shibayama teaches the use of a PD-1 agonist for the treatment of an autoimmune disease, wherein the autoimmune disease is selected from a group comprising type 1 diabetes mellitus ([0012] and [0020]).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to (1) combine the agonist PD-1 antibodies of Alt with an immunosuppressive agent selected from the claimed list of known autoimmune disease therapeutics, (2) to conjugate the immunosuppressive agent to the antibody and (3) use the anti-PD1 antibody of Alt in a method to treat an autoimmune disorder or to suppress an immune response. One would have been motivated to do so because (1) Alt and Shibayama both teach the PD-1 antibodies of the disclosures are administered as part of combination therapy, (2) Alt teaches conjugation of drugs to the PD1 agonist antibody, a known method of targeted drug delivery and (3) Shibayama teaches that agonist PD1 antibodies can be used to treat autoimmune diseases due to their ability to modulate T cell activity. The disclosure of Alt does not specifically disclose which anti-PD1 antibodies are inherently agonist, however Alt provides the anti-PD1 antibodies for which the agonist mechanism of action could readily be determined pointing to their use in modulating autoreactive T cells. Further, combination therapy for the treatment of autoimmune disease, particularly when the therapeutics have different mechanisms of actions (e.g. PD-1 agonist antibody and fingolimod) is widely practiced in the art. There would be an expectation of success in combining the teachings of Alt and Shibayama because Alt provides antibodies that can readily be used in in clinical setting for treating subject with autoimmune diseases.
Response to Applicant’s Remarks
Applicant's arguments filed 07/21/2026 have been fully considered but they are not persuasive.
The Applicants submit that Alt fails to disclose or suggest the presently claimed invention and Shibayama fails to remedy those defects. Shibayama is alleged to teach no more than conjugation of antibodies to agents and anti-PD1 antibodies generally for treatment of autoimmune disorders. Therefore, no combination of Alt and Shibayama can render the claimed invention obvious. (Remarks, Pg. 2)
In response, the rejection has been updated to address the amended limitations. While Alt teaches the anti-PD1 antibody can be co-administered or conjugated to additional therapeutic agents, Alt does not specifically disclose this teaching in the context of treating autoimmune disease. Shibayama does indeed cure this deficiency teaching that PD-1 agonist antibodies can be used to treat autoimmune diseases and that PD-1 agonist antibodies can be co-administered with known autoimmune therapeutics. Shibayama specifically states that the antibodies of their disclosure can be used in combination with fingolimod for treating multiple sclerosis and SLE ([0244]-[0245]. Combination therapy for autoimmune diseases is standard practice in the field. In the case of co-administration of a PD1 agonist with fingolimod, the combination treatment provides two different mechanisms of treating autoimmune disease: (1) stimulation of PD-1 through agonist antibodies promotes self-tolerance by suppressing autoreactive T cells and (2) fingolimod prevents egress of T cells out of the thymus and secondary lymphoid organs, lowering the number of circulating lymphocytes. As both treatments are indicated for treating autoimmune disease, it would be obvious to combine them.
For this reason, the examiner maintains the rejection of claims 17-18, 27-29, 33, and 69-71 under 35 U.S.C. 103 as being unpatentable over Alt and Shibayama.
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.
US11,427,636B2
Claims 17-18, 27-29, 33, and 69-71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,427,636 B2 in view of Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) and Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
Regarding instant claim 17, pertaining to a composition comprising the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 or additionally disclosed antibody and (ii) an immunosuppressive agent, ‘636 discloses four of the instant antibodies shown below:
Clone Name
Instant
US11427636B2
319-9-75
CDRs SEQ ID NO: 11-16
Heavy chain SEQ ID NO: 9
Light chain SEQ ID NO: 10
CDRs SEQ ID NO: 71-76
319-9-27
CDRs SEQ ID NO: 27-32
Heavy chain SEQ ID NO: 25
Light chain SEQ ID NO: 26
CDRs SEQ ID NO: 41-46
Heavy chain SEQ ID NO: 7
Light chain SEQ ID NO: 8
319-9-34
CDRs SEQ ID NO: 43-48
Heavy chain SEQ ID NO: 41
Light chain SEQ ID NO: 42
CDRs SEQ ID NO: 53-58
Heavy chain SEQ ID NO: 11
Light chain SEQ ID NO: 12
319-9-53
CDRs SEQ ID NO: 59-64
Heavy chain SEQ ID NO: 57
Light chain SEQ ID NO: 58
CDRs SEQ ID NO:35-40
Heavy chain SEQ ID NO: 5
Light chain SEQ ID NO: 6
Regarding caim 69, wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 17 further comprises a conservative substitution in a sequence not comprised by a CDR, ‘636 claim 5 discloses wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 further comprises a conservative substitution in a sequence not comprised by a CDR.
Regarding claim 70, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is fully humanized except for the CDR sequences, ‘636 claim 6 discloses the antibody, antibody reagent, antigen-binding portion thereof, or CAR is fully humanized except for the CDR sequences.
Regarding claim 71, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is selected from is selected from the list of disclosed group of antibody formats, ‘636 claim 8 discloses wherein the antibody is an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody.
‘636 does not teach: (1) the composition, kit or combination of the disclosure further comprises an immunosuppressive agent from the list disclosed in claim 17, (2) the immunosuppressive agent is conjugated to the antibody or (3) administration of the anti-PD1 antibody for the treatment of an autoimmune disorder or for suppressing an immune response.
These deficiencies are taught by Alt and Shibayama.
Regarding the limitation of claim 17 wherein the composition, kit or combination further comprises an immunosuppressive agent selected from the discloses list, Shibayama teaches use of the PD-1 agonist antibody of the disclosure for the treatment of autoimmune diseases such as multiple sclerosis and SLE in combination with autoimmune therapeutics including fingolimod ([0244]-[0245]).
Regarding claim 18, wherein the antibody, antibody reagent, or antigen-binding portion thereof of the composition, kit or combination of claim 17 is conjugated to the immunosuppressive agent, Alt teaches that antibody of the disclosure used in an antibody-drug conjugate (Pg. 17, claim 18) and Shibayama teaches combinationatorial administration of the agonist PD-1 antibodies with known autoimmune therapeutics ([0244]-[0245]).
Regarding claims 27-29 and 33, pertaining to a method of treating an autoimmune disorder, wherein the autoimmune disorder is a T cell-mediated disorder selected from the group disclosed in claim 29 (claim 27-29) and a method of suppressing an immune response in a subject (claim 33) comprising administration of an antibody of the disclosure, Shibayama teaches the use of a PD-1 agonist for the treatment of an autoimmune disease, wherein the autoimmune disease is selected from a group comprising type 1 diabetes mellitus ([0012] and [0020]).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to (1) combine the agonist PD-1 antibodies of ‘636 with an immunosuppressive agent selected from the claimed list of known autoimmune disease therapeutics, (2) to conjugate the immunosuppressive agent to the antibody and (3) use the anti-PD1 antibody of Alt in a method to treat an autoimmune disorder or to suppress an immune response. One would have been motivated to do so because (1) Alt and Shibayama both teach the PD-1 antibodies of the disclosures are administered as part of combination therapy, (2) Alt teaches conjugation of drugs to the PD-1 agonist antibody, a known method of targeted drug delivery and (3) Shibayama teaches that agonist PD1 antibodies can be used to treat autoimmune diseases by modulating the activity of autoreactive T cells. Further, combination therapy for the treatment of autoimmune disease, particularly when the therapeutics have different mechanisms of actions (e.g. PD-1 agonist antibody and fingolimod) is widely practiced in the art. There would be an expectation of success in combining the teachings of ‘636, Alt and Shibayama because ‘636 provides antibodies that can readily be used in in clinical setting for treating subject with autoimmune diseases.
U.S. Application No. 17/870, 010 Notice of Allowance Mailed 05/30/2025
Claims 17-18, 27-29, 33,and 69-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, and 15-16 of copending Application No. 17/870, 010 in view of Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) and Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
Application 17/870, 010 is a DIV of U.S. Pat. No. 11,427,636 B2 directed to the nucleic acids encoding the instant anti-PD1 antibody. The rejection of U.S. Pat. No. 11,427,636 B2 outlined above is incorporated herein.
This is a provisional nonstatutory double patenting rejection.
U.S. Application No. 19/264,986
Claims 17-18, 27-29, 33, and newly added 69-71 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 19/264,986 in view of Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) and Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
Application 19/264,98 is a DIV of U.S. Pat. No. 11,427,636 B2 directed to the nucleic acids encoding the instant anti-PD1 antibody. The rejection of U.S. Pat. No. 11,427,636 B2 outlined above is incorporated herein.
This is a provisional nonstatutory double patenting rejection.
Response to Remarks
Applicant's arguments filed 07/21/2026 have been fully considered but they are not persuasive.
The applicant requests reconsideration and withdrawal of the above double patenting rejections because the above cited patent and applications fail to teach the combination of claim 17 in view of the combined teachings of Alt and Shibayama (Remarks, Pg. 2).
In response, the examiner reaffirmed the obviousness of combination therapy comprising PD-1 agonist antibodies co-administered or conjugated to known autoimmune therapeutics as taught by Shibayama. For this reason, the double patenting rejections are maintained herein.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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