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 .
Claims 1, 3-7, 9-10, 13-15, 17-18, and 22-28 are pending.
Election/Restrictions
Applicant’s election without traverse of the species election in the reply filed on 10/02/2025 is acknowledged. To reconfirm, applicants have elected the following species of bispecific molecule:
PNG
media_image1.png
140
682
media_image1.png
Greyscale
PNG
media_image2.png
110
664
media_image2.png
Greyscale
Upon reconsideration and searching, the species election of SEQ ID NO:130 has been extended to include SEQ ID NO:122 (see claim 3).
Specification
The specification is objected to on page 42. The list of linkers and examples is not very discernable (blurry image). It further includes numbers corresponding to references (Ref.) which doesn’t appear to be a part of the present specification. Also, many of the linker amino acid sequences do not contain the necessary SEQ ID Nos. See 37 CFR 1.821(c).
Claim Rejections - 35 USC § 112
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.
Claim 18 is 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. Claim 18 recites a “binding moiety” as an alternative structure of an antibody or antibody binding fragment. However, it’s unclear what structure encompasses such a generic term and the specification does not provide a definition of what is included by the term “binding moiety”. Thus, one of ordinary skill in the art would not understand the metes and bounds of this limitation.
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.
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 1, 3-7, 9-10, 13-15, 24-28 is/are rejected under 35 U.S.C. 103 as being obvious over US Patent 11250546 (Fang et al., March 29, 2018) and US Patent 11891445 (Park et al., May 2018).
The applied references have commonality (inventorship/assignee) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The claims are drawn to bispecific antibodies targeting PD-L1 and B7-H3. The PD-L1 antibody has the following elected species of CDRs:
VHCDR1
SYDMS
SEQ ID NO:1
VHCDR2
TISDAGGYIYYRDSVKG
SEQ ID NO:3
VHCDR3
ELPWRYALDY
SEQ ID NO:5
VLCDR1
KASQDVTPAVA
SEQ ID NO:12
VLCDR2
STSSRYT
SEQ ID NO: 15
VLCDR3
QQHYTTPLT
SEQ ID NO:16
Fang et al. teach and claim an anti-PD-L1 antibody with 100% identity to the above six CDRs. For example, see column 18:
PNG
media_image3.png
300
448
media_image3.png
Greyscale
PNG
media_image4.png
362
404
media_image4.png
Greyscale
As to claim 3, the elected species of the variable light chain comprising the above CDRs was SEQ ID NO:130. While Fang et al. teach a VL chain with 98.4% identity to SEQ ID NO:130, said VL chain only comprises 5 of the elected CDRs (see search result 7 of 17-778-482a-130.rai). Thus, the species search was extended to SEQ ID NO:122. Fang et al. teach and claim a variable light chain with 100% identity to SEQ ID NO:122. Below is the sequence comparison between applicant’s SEQ ID NO:122 (Qy) which matched to Fang’s SEQ ID NO:150 (Db):
PNG
media_image5.png
278
752
media_image5.png
Greyscale
Regarding claim 5, the elected species of the variable heavy chain comprising the above CDRs was SEQ ID NO:129. Fang et al. teach and claim a VH domain of an anti-PD-L1 antibody with 100% identity to SEQ ID NO:129 comprising all 6 elected species of CDRs:
PNG
media_image6.png
718
644
media_image6.png
Greyscale
Th above matched to Fang’s SEQ ID NO:149. Fang et al. claim both Vh and Vl chains:
PNG
media_image7.png
88
442
media_image7.png
Greyscale
As to claim 7, Fang et al. teach [0006] that the anti_PD-L1 antibody is capable of binding to at lest one of amino acids Y134, K162, and N183.
Regarding claim 9, Fang et al teach [0008] without limitation, the antibody or fragment thereof is a chimeric antibody, a humanized antibody, or a fully human antibody.
Regarding claims 10 and 14, Fang et al. teach [0062] that antibodies, antigen-binding polypeptides, variants, or derivatives thereof of the disclosure include, but are not limited to, polyclonal, monoclonal, multispecific, human, humanized, primatized, or chimeric antibodies, single chain antibodies, epitope-binding fragments, e.g., Fab, Fab′ and F(ab′)2, Fd, Fvs, single-chain Fvs (scFv), single-chain antibodies, disulfide-linked Fvs (sdFv), fragments comprising either a VK or VH domain, fragments produced by a Fab expression library, and anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id antibodies to LIGHT antibodies disclosed herein). Immunoglobulin or antibody molecules of the disclosure can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass of immunoglobulin molecule.
Regarding claim 13, Fang et al. teach [0256,0262] that the anti-PD-L1 antibodies can further comprise an antagonist that targets 4-1-BB.
Regarding claims 24-28, Fang et al. [0019-0020] teach pharmaceutical compositions of the antiPD-L1 antibodies for treating bladder cancer, liver cancer, colon cancer, rectal cancer, endometrial cancer, leukemia, lymphoma, pancreatic cancer, small cell lung cancer, non-small cell lung cancer, breast cancer, urethral cancer, head and neck cancer, gastrointestinal cancer, stomach cancer, oesophageal cancer, ovarian cancer, renal cancer, melanoma, prostate cancer and thyroid cancer.
Fang et al. further teach [0023] that antibodies and fragment of the present disclosure can be used to prepare bispecific antibodies. In one embodiment, a bispecific antibody is provided, comprising a fragment of the present disclosure and a second antigen-binding fragment having specificity to a molecular on an immune cell. In some embodiments, the molecule is selected from the group consisting of PD-1, CTLA-4, LAG-3, CD28, CD122, 4-1BB, TIM3, OX-40, OX40L, CD40, CD40L, LIGHT, ICOS, ICOSL, GITR, GITRL, TIGIT, CD27, VISTA, B7H3, B7H4, HEVM or BTLA, CD47 and CD73.
However, Fang et al. does not specifically teach the claimed anti-B7-H3 antibody structure as claimed in Claim 1.
The B7-H3 antibody has the following elected species of CDRs:
VHCDR1
GYYMS
SEQ ID NO:21
VHCDR2
LISPSSGSIYYADSVKG
SEQ ID NO:25
VHCDR3
GLTKFDY
SEQ ID NO:31
VLCDR1
TGSSSNIGSNDVS
SEQ ID NO:36
VLCDR2
ANSHRPS
SEQ ID NO: 41
VLCDR3
GSWDDSLSGYV
SEQ ID NO:47
Park et al. teach and claim an anti-B7-H3 antibody (C4I) comprising all claimed species of CDRs:
PNG
media_image8.png
434
564
media_image8.png
Greyscale
PNG
media_image9.png
398
586
media_image9.png
Greyscale
PNG
media_image10.png
428
428
media_image10.png
Greyscale
As to claim 4, Park et al. further teach and claim that the anti-B7H3 antibody (clone C4I) comprises a VL chain with 100% identity to SEQ ID NO:58. (Park’s VL is SEQ ID NO:36).
PNG
media_image11.png
718
726
media_image11.png
Greyscale
As to claim 6, Park et al. teach and claim that the anti-B7H3 antibody (clone C4I) comprises a VH chain with 100% identity to SEQ ID NO:58. (Park’s VL is SEQ ID NO:31).
PNG
media_image12.png
722
640
media_image12.png
Greyscale
PNG
media_image13.png
168
424
media_image13.png
Greyscale
As to claims 9-10, (Similar to Fang et al. above), Park et al teach that the antibodies can be chimeric humanize or a fully human antibody (column 13, last para). Park et al. further teaches (column 17, lines 29+) that the antibody fragment of the antibody disclosed herein may be Fab, Fab', F(ab')2, scFab, Fv, 30 dsFv, scFV, scFV-Fc, minibody, diabody, scab, or dAb.
As to claims 24-27, Park et al. (Column 5, lines 58+) teach a composition or pharmaceutical composition comprising the antibody or its antigen binding fragment and a pharmaceutically acceptable excipient. In one embodiment, the pharmaceutical composition is a pharmaceutical composition for treating and/or preventing a disease, for example, cancer.
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to form a bispecific antibody by combining the teachings of both Fang et al. and Park et al. because Fang et al. specifically teaches that the anti-PD-L1 antibody can be used to prepare bispecific antibodies wherein the second antigen-binding fragment has specificity to B7H3. Also, separately, Park et al. taught the efficacy of combining anti-B7-H3 antibodies and anti-PD-1 antibodies in a mouse tumor model (Figure 11). Thus, one would have been clearly motivated to make the claimed bispecific antibodies for the purposes of gaining a greater therapeutic effect versus targeting the antigens separately. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
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, 3-6, 9-10, 15, 24-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, and 8-19 of U.S. Patent No. 11220546 AND over claims 1-12 of U.S Patent No. 11891445. Although the claims at issue are not identical, they are not patentably distinct from each other.
As set forth in the 103 rejection above, each patent (separately) claims an anti-PDL1 antibody comprising the same CDRs and the same VH, and VL regions as claimed and an anti-B7H3 antibody comprising the same CDRs and the same VH, and VL regions as claimed. Each patent claims pharmaceutical compositions and methods of treating cancer with their antibodies. Further, Claims 8 and 9 of US Patent 11220546 claim bispecific antibodies to B7H3. It would have been obvious to combine the two claim sets in order to form a more potent bispecific antibody for greater therapeutic purposes as both targeted antigens were well-known at time of filing and both PD-L1 and B7H3 are well recognized as immune checkpoint molecules.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 15, 17-18, 22-23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US20180346573A1 (Fang et al., published December 6, 2018).
As to claim 15, Fang et al. teach [0019] teach that anti-PD-L1 antibodies can be used to prepare bispecific antibodies. In one embodiment, an isolated bispecific antibody is provided, comprising a fragment of the present disclosure and a second antigen-binding fragment having specificity to a molecule on an immune cell. In some embodiments, the molecule is B7H3. The antibodies [0052], antigen-binding polypeptides, variants, or derivatives thereof encompass , human and humanized formats which would inherently bind human PD-L1 and human B7H3 proteins.
As to claim 16, 18, the reference teaches [0107] that different formats of bispecific antibodies are also provided. In some embodiments, each of the anti-PD-L1 fragment and the second fragment each is independently selected from a Fab fragment, a single-chain variable fragment (scFv), or a single-domain antibody. In some embodiments, the bispecific antibody further includes a Fc fragment. Thus, in some of these configurations, both antigen binding regions would be located at the N-terminal side of the Fc fragment.
Regarding claims 22-23, the reference teaches [0006] one embodiment of the present disclosure provides an anti-PD-L1 antibody or fragment thereof, which antibody or fragment thereof can specifically bind to an immunoglobulin C (Ig C) domain of a human Programmed death-ligand 1 (PD-L1) protein. In some embodiments, the Ig C domain consists of amino acid residues 133-225. In some embodiments, the antibody or fragment thereof can bind to at least one of amino acid residues Y134, K162, or N183 of the PD-L1 protein.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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, Julie Wu can be reached at 571-272-5205. 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.
/GARY B NICKOL/Primary Examiner, Art Unit 1643