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 .
Response to Amendment
In the amendment filed on 06/29/2026, Applicant amended claims 1-3, 6-12, 15-17 and 20, and cancelled claim 4 and 5. Claims 1-3 and 6-20 are pending and are examined.
New and Maintained claim rejections
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 1-3, 18-20 remain and claims 6-15 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
As indicated in the previous Office action,
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’”
The claims broadly encompass any bispecific antibody that binds PD-L1 and CD47.
The PD-L1 antibody has the 6 CDRs comprising:
(a) a VHa CDR1 comprising an amino acid sequence set forth in any one of SEQ
IDNOs: 4-8;
(b) a VHa CDR2 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 9-18;
(c) a VHa CDR3 comprising an amino acid sequence set forth in SEQ ID NO:
19 or 20;
( d) a VLa CDR1 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 36-40;
( e) a VLa CDR2 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 41-44; and
(f) a VLa CDR3 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 45-48.
The CD47 antibody has the 6 CDRs comprising:
(g) a VHb CDR1 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 21-23:
(h) a VHb CDR2 comprising the amino acid sequence set forth in any one of SEQ ID NOs: 24-28:
(i) a VHb CDR3 comprising the amino acid sequence set forth in any one of SEQ
ID NOs: 29-35:
(j) a VLb CDR1 comprising the amino acid sequence set forth in any one of SEQ
ID NOs: 36-40:
(k) a VLb CDR2 comprising the amino acid sequence set forth in any one of SEQ
ID NOs: 41-44: and
(1) a VLb CDR3 comprising the amino acid sequence set forth in any one of SEQ
ID NOs: 45-48.
According to the claims, the number of possible antibodies that may comprise the
variable chain domains of the anti-PD-L1 antibody is ~6,000 (considering all the possible arrangements of the CDRs disclosed), and for the anti-CD47 antibody, ~8,900. Thus, the number of bispecific antibodies possible if ~5x107.
To represent this huge number, the Specification disclosed only BsAb-36, BsAb- 46, BsAb-47, BsAb-71, BsAb-71-N297A (5 bispecific antibodies).
The instant specification does not describe representative number of species to support the full scope of the claims because the instant specification discloses only 5 bispecific antibodies.
A “representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
If Applicant is in possession of other bispecific antibodies that bind PD-L1 and CD47 they are kindly prompted to present them for examination. Until then, the only species that Applicant in in possession of are only BsAb-36, BsAb- 46, BsAb-47, BsAb-71, BsAb-71-N297A.
Claims 1-3, 6-15 and 18-20 remain 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 bispecific antibodies comprising full 6 CDRs sets in a set order (e.g. BsAb-36, BsAb-46, BsAb-47, BsAb-71, BsAb-71-N297A) does not reasonably provide enablement for antibodies characterized by less than a full set of CDRs. does not reasonably provide enablement for full scope of claim 1. 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.
To recapitulate, the claims are drawn to a bispecific antibody or an antigen-binding fragment, wherein the antibody or the antigen-binding fragment comprises a variable region a specifically binding to PD-L1, wherein the variable region a comprises one or more amino acid sequences of (a)-(f):
(a) a VHa CDR1 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 4-8;
(b) a VHa CDR2 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 9-18;
(c) a VHa CDR3 comprising an amino acid sequence set forth in SEQ ID NO:
19 or 20;
( d) a VLa CDR1 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 36-40;
( e) a VLa CDR2 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 41-44; and
(f) a VLa CDR3 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 45-48.
The antibody or the antigen-binding fragment specifically binding to CD47 comprises a variable region b, wherein the variable region b comprises one or more amino acid sequences of (g)-(l):
(g) a VHb CDR1 comprising an amino acid sequence set forth in any one of
SEQ ID NOs: 21-23;
(h) a VHb CDR2 comprising an amino acid sequence set forth in any one of
SEQ ID NOs: 24-28;
(i) a VHb CDR3 comprising an amino acid sequence set forth in any one of
SEQ ID NOs: 29-35;
(g) a VLb CDR1 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 36-40;
(k) a VLb CDR2 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 41-44; and
(i) a VLb CDR3 comprising an amino acid sequence set forth in any one of SEQ
ID NOs: 45-48.
The antibody or the antigen-binding fragment further comprises a heavy chain constant region a and a heavy chain constant region b, wherein the heavy chain constant region a and the heavy chain constant region b are linked to the heavy chain variable region a and the heavy chain variable region b, respectively, and the heavy chain constant region a and/or the heavy chain constant region b comprise one or more of the following amino acid mutations in which amino acid positions are Eu numbered:
Y349C, S354C, T366W, T366S, L368A, Y407V, N297A, T366W and Y407V.
According to the claim limitations, the number of possible antibodies that may comprise the variable chain domains of the anti-PD-L1 antibody is ~6,000, and for the anti-CD47 antibody, ~8,900. Thus, the number of bispecific antibodies possible if ~5x107. Also, the specificity of the antibody is conferred by a set of 6CDRs in an organized arrangement and not by randomly picking each CDR from a list of sequences.
The specification discloses only BsAb-36, BsAb-46, BsAb-47, BsAb-71, BsAb-71-N297A.
While the art of antibody manufacturing is relatively advanced, there is still a high level of polymorphism of immunoglobulins/antibodies. Obtaining of antibodies and, even further, bispecific antibodies, is not yet a trivial matter since each antibody needs to be painstakingly tested.
Obtaining and testing the bispecific antibody as claimed instantly would necessitate an immense experimental endeavor and is submitted that such a feat represent un undue burden.
On pages 11-12 of the Remarks Applicant argues that the Application is enabled in its full scope. The arguments were carefully considered but not found persuasive.
The quantity of the experimentation needed is enormous, given the large number of potential compounds that may be envisioned.
Applicant argues that : “The breadth of the claims is limited to bispecific antibodies having all of the 6 recited CDRs of the anti PD-L1 antibodies and all of the 6 recited CDRs of the anti CD47 antibodies. Therefore, a person of ordinary skill in the art seeking to practice the claims would have no need to engage in de novo antibody discovery, since the presently claimed antibodies are fully characterized by their structure.” This is not persuasive because each of the specific antibodies needs to be described by one set of 6 CDRs for the anti-PD-L1 antibody and one set of 6 CDRs for the anti-CD47 antibody claim 1 let the person of ordinary skill in the art to pick and choose from various CDR and thus the number of the possible constructs becomes forbiddingly large.
Contrary to Applicant’s contention that the amount of direction and guidance in the specification is enough for the enablement, Applicant’s attention is drawn to the fact that there is no direction or indication as to how the CDRs of the claim 1 are to be paired so as to form a functioning antibody; the only exception is present in claims 16 and 17.
Regarding the number of working examples, Applicant is again reminded that only 5 antibodies are presented.
While the art of antibody manufacturing is relatively advanced, there is still a high level of polymorphism of immunoglobulins/antibodies. Obtaining of antibodies and, even further, bispecific antibodies, is not yet a trivial matter since each antibody needs to be painstakingly tested. Obtaining and testing the bispecific antibody as claimed instantly would necessitate an immense experimental endeavor and is submitted that such a feat represent un undue burden.
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.
Claim 1-3 and 6-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of copending Application No. 18/681,485 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the antibodies claimed in the reference application (comprising the CDR sets of SEQ ID NOs: 1-9) have the same structure with the bispecific antibody having the CDR sets of SEQ ID NOs: 4, 14, 19, 36, 41, 45, and 21, 24 and 29, respectively. The structures being the same, the properties (potentially treating a disease) are the same. If the reference application is allowed first, the instant application would be anticipated by the reference Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
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.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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