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 .
Status of the Claims
Claims 75 – 101 are currently pending, with claims 75 – 82, 87 – 93 and 98 – 101 withdrawn from consideration as being directed to nonelected subject matter. Claims 83 – 86 and 94 - 97 are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Election/Restrictions
Applicant’s elections without traverse of Group I and species of SEQ ID NOs: 135 and 144 in the reply filed 04/24/2026 to the Requirement for Restriction/Election of 02/24/2026 is acknowledged.
On p. 1, last paragraph, of the reply, Applicant states that claims 83 – 86 and 97 read on both the elected group and the elected species. Claims 83 – 86 and 97 are examined on the merits.
In view of Applicant’s elections in the reply, the following restriction is applied:
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 75 – 82 and 98, drawn to a fusion protein comprising (1) a first domain comprising an antibody that binds Programmed Death Ligand 1 (PD-L1), or an antigen-binding fragment thereof, (2) a transferrin linker, and (3) a second domain comprising a fragment of transforming growth factor p receptor type 2 (TGFbRII) that binds transforming growth factor b (TGFb), or a variant thereof; an antibody or antigen-binding fragment thereof that binds PD-L1; a polynucleotide; a vector; an isolated cell; and a pharmaceutical composition classified in C07K 2319/00.
II. Claims 83 – 86, 94 – 96 and 97, drawn to an antibody or antigen-binding fragment thereof that binds PD-L1 and a pharmaceutical composition classified in C07K 16/28.
III. Claims 87 – 93, drawn to a fusion protein comprising a first domain comprising the antibody or antigen- binding fragment of claim 83 and a second domain comprising a fragment of TGFbRII that binds TGFb, or a variant thereof classified in C07K 2319/00.
IV. Claims 99 – 101, drawn to a method of treating tumor or cancer in a subject in need thereof, classified in A61P 35/00.
The inventions are independent or distinct, each from the other because:
Inventions I - III are directed to related products. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed have different structures and thus different mechanisms of function. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants.
Inventions I - III and IV are related as products and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, the fusion protein or antibody can be used in treating tumor or cancer, can be used in antibody production, or can be used in an assay to detect cancer.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
(d) the prior art applicable to one invention would not likely be applicable to another invention;
(e) the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
In particular the inventions have acquired a separate status in the art in view of their different classification and the inventions require a different field of search.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Election of Species
This application contains claims directed to the following patentably distinct species of a fusion protein or antibody.
Applicant is required to elect and specifically define a single fusion protein, fusion-protein variant, antibody, or antigen-binding fragment, and its sequence(s), with each position on the amino acid sequence(s) of the single fusion protein, fusion-protein variant, antibody, or antigen-binding fragment defined, including any modifications such as mutations. Any SEQ ID NOs related to the elected single fusion protein, fusion-protein variant, antibody, or antigen-binding fragment must be specified.
The species are independent or distinct because the species have mutually exclusive characteristics for each identified species. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, no claim is generic.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply: the species or groupings of patentably indistinct species require a different field of search (e.g., searching different classes /subclasses) or electronic resources, or employing different search strategies or search queries.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
During a telephone conversation with Xiaoxiang Liu on 06/03/2026 a provisional election was made without traverse to prosecute the invention of Group II, claims 83 – 86, 94 - 97. Affirmation of this election must be made by applicant in replying to this Office action. Claims 75 – 82, 87 – 93 and 98 – 101 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/26/2023 is in compliance with the provisions of 37 CFR 1.97 and has been considered.
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 83 – 86 and 94 – 97 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
The following quotation from section 2163 of the Manual of Patent Examination Procedure (MPEP) is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 83 – 86 and 94 – 97 are rejected as lacking adequate descriptive support for a possession of a generic antibody or antigen-binding fragment thereof that binds PD-L1. Independent claim 83 recites “a heavy chain variable region (VH) . . . or a variant thereof having up to about 5 amino acid substitutions, additions, and/or deletions in the VH CDRs; and/or (b) a light chain variable region (VL) . . . or a variant thereof having up to about 5 amino acid substitutions, additions, and/or deletions in the VL CDRs”. Thus, 1) multiple alternatives for the VH CDRs are claimed; 2) because the claim recites “and/or”, both VH and VL of the antibody are not required; and 3) multiple alternatives for the VL CDRs are claimed. This results in a large variety of heavy, light chain variable domains, and antibodies or antigen-binding fragments thereof, all of which are not supported by the present specification. In addition, because the 5 amino acid substitutions, additions, and/or deletions are directed to the CDRs, the resulting VH, VL and antibody may possibly not be able to bind PD-L1.
Furthermore, because VL is listed after the coordinating conjunctions “and/or”, the “or” allows the VL to be an alternative and thus not required in the structure of the antibody or antigen-binding fragment thereof. However, the present application does not provide an antibody or antigen-binding fragment thereof that binds PD-L1 that is enabled without a VH or a VL. Thus, the claims lack written description of an antibody or antigen-binding fragment thereof that binds PD-L1 and is enabled as claimed.
The specification presents 13 variants of the VH and 13 variants of the VL for the anti-PD-L1 antibodies (Table 1 and Table 2, pages 38 – 39), and thus, the number of variants is not commensurate in scope with the present claims. The structure of all the possible variants are not disclosed.
Moreover, in Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the
Supreme Court, held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). See MPEP 2164.01.
Presently, the claimed antibody composition used is only defined by functional properties: its ability to bind PD-L1. Because multiple positions on the heavy and light chain CDRs can vary significantly, the structure of the antibody or antigen-binding fragment thereof that binds PD-L1 is not specific. For example, the antibody or antigen-binding fragment thereof that binds PD-L1 can bind any epitope of PD-L1. In view of the fact patterns detailed in Amgen v. Sanofi, applicants are not in possession of such an antibody which can bind to any epitope presented by the claimed antibody or antigen-binding fragment thereof that binds PD-L1 .
Providing SEQ ID NOs for the antibody or antigen-binding fragment thereof that binds PD-L1 with all of the CDRs 1-3 of the VH chain AND all of the CDRs 1-3 of the VL chain that represent specific sequences with each position of the sequence defined with a specific amino acid for claims 83 – 86 and 97 can provide sufficient structure(s) of the claimed antibodies or antibody fragments.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
Claim 86 is 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 other limitations of the claim, does not reasonably provide enablement for a human antibody or antigen-binding fragment thereof. 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.
In particular, claim 86 recites a human antibody. a human antibody is an antibody, including the CDRs, that is of human origin. While one can envision a chimeric or humanized antibody given the antibodies disclosed in the present application, one cannot envision the structure of a human antibody, at least because it would be expected to have different CDRs. The specification does not provide any suggestion that the CDRs of claim 83, from which 86 depends, exist in human antibodies that target PD-L1. Rather, the specification discloses CDRs that are of mouse origin (Example 1, paragraph 00410, p. 154).
Claim Rejections - 35 USC § 102
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 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.
Claims 83 – 86 and 94 – 97 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by TSURUSHITA (WO 2020/102233-A1, published 05/22/2020; see PTO-892: Notice of References Cited).
According to the present specification, Applicant’s elected species of Clone B of an anti-PD-L1 antibody consists of a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 27, and SEQ ID NO: 28, respectively (Table 1, p. 38 of the specification) and a VL CDR1, a VL CDR2, a VL CDR3 having the amino acid sequences of SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, respectively (Table 2, p. 38 of the specification).
TSURUSHITA is directed to bispecific antibodies having one arm binding to a cancer associated antigen on a cancer cell, such as CD33, EGFR or PD-L1, and a second arm binding to a costimulatory molecule, such as 0X40, CD40, GITR, ICOS or 4-1BB. Bridging by the bispecific antibody between cancer cells expressing the cancer associated antigen and immune cells expressing the costimulatory molecule results in clustering of the costimulatory molecules and selective activation of the immune cells at a location proximate to the cancer cells. TSURUSHITA teaches that the immune cells can exert an immunotherapeutic effect against the cancer cells with reduced toxicity to healthy tissue. See TSURUSHITA at the abstract.
Regarding claim 83, “an amino acid sequence selected from the group consisting of SEQ ID NOs: . . . 26 . . ." or “an amino acid sequence selected from the group consisting of SEQ ID NOs: . . . 27. . ." or “an amino acid sequence selected from the group consisting of SEQ ID NOs: . . . 28. . .", etc. each reads on a sequence that may be a fragment or portion of the CDR sequence represented by the SEQ ID NOs of the claim. In other words, because the phrase “an amino acid sequence” includes of “an” (an indefinite article) instead of “the” (a definite article; i.e. “the amino acid sequence”) in the beginning of the phrase, the phrase is not definite for the sequence of the SEQ ID NO and can read on fragments of that sequence. Additionally, claim 83 specifically recites a variant thereof having up to about 5 amino acid substitutions, additions, and/or deletions in the VH or VL CDRs.
TSURUSHITA’s SEQ ID NO: 61 teaches VH CDR1 and VH CDR2 with 100% identity. Although TSURUSHITA’s SEQ ID NO: 61 teaches a VH CDR3 that differs by one amino acid (see Appendix), because the claimed CDRs read on fragments, TSURUSHITA’s SEQ ID NO: 61 reads on the elected species of VH CDRs having SEQ ID NOs: 26 – 28 of claims 83 – 84. See ¶¶ 0010, 0013 and Appendix.
Similarly, TSURUSHITA’s SEQ ID NO: 65 teaches VL CDR2 and VL CDR3 with 100% identity. Although TSURUSHITA’s SEQ ID NO: 65 teaches a VL CDR1 that differs by one amino acid (see Appendix), because the claimed CDRs read fragments, TSURUSHITA’s SEQ ID NO: 65 reads on the elected species of VL CDRs having SEQ ID NOs: 29 – 31 of claims 83 – 84. See ¶¶ 0010, 0065 and Appendix.
Regarding claim 85, TSURUSHITA teaches an anti-PD-L1 VH and VL having the sequences of SEQ ID NOs: 135 and 144, respectively. TSURUSHITA’s SEQ ID NO: 61 teaches present SEQ ID NO: 135 with 93.6% identity. TSURUSHITA’s SEQ ID NO: 65 teaches present SEQ ID NO: 144 with 94.7% identity. See Appendix.
Regarding claim 86, Clone B binds PD-L1 from cells with different glycosylation status. See Fig. 1 of the instant specification. Thus, given that the anti-PD-L1 antibody of TSURUSHITA has the same structure as claimed, it would have the same function as claimed, i.e. binding to glycosylated PD-L1.
Regarding claims 94 – 96, TSURUSHITA teaches a polynucleotide, a vector, and an isolated cell comprising the polynucleotide. See ¶¶ 0079- 0088.
Regarding claim 97, TSURUSHITA teaches the invention further provides a pharmaceutical composition comprising any of the bispecific or monoclonal antibodies and a pharmaceutically acceptable carrier. See ¶ 0014.
It would have been prima facie obvious to the person of ordinary skill in the art, at the effective filing date of the claimed invention, to arrive at the claimed invention from the disclosures of TSURUSHITA. The artisan would have been motivated to make and use an antibody or antigen-binding fragment thereof that binds PD-L1 because TSURUSHITA teaches that the antibodies activate immune cells which can exert an immunotherapeutic effect against the cancer cells with reduced toxicity to healthy tissue. Thus, the artisan would have a reasonable expectation of success from the teachings of TSURUSHITA.
Conclusion
Claims 83 – 86 and 94 – 97 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
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, Gregory Emch can be reached at 571-272-8149. 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.
/ESTELLA M. GUSTILO/ Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment with SEQ ID NOs: 26 – 28
BHU89178
ID BHU89178 standard; protein; 138 AA.
XX
AC BHU89178;
XX
DT 09-JUL-2020 (first entry)
XX
DE Anti-PD-L1 humanizied antibody heavy chain variable region, SEQ:61.
XX
KW CD274; PD-L1 protein; Programmed cell death ligand 1;
KW antibody engineering; antibody therapy; antimicrobial-gen.; cancer;
KW cytostatic; heavy chain variable region; humanizied antibody;
KW infectious disease; prophylactic to disease; therapeutic.
XX
OS Mus sp.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..19
FT /label= Signal_peptide
FT Protein 21..138
FT /label= Mature_protein
FT /note= "Specifically claimed in claim 5"
XX
CC PN WO2020102233-A1.
XX
CC PD 22-MAY-2020.
XX
CC PF 12-NOV-2019; 2019WO-US060982.
XX
PR 13-NOV-2018; 2018US-0760328P.
PR 25-APR-2019; 2019US-0838579P.
XX
CC PA (JNBI-) JN BIOSCIENCES LLC.
XX
CC PI Tsurushita N, Tso JY;
XX
DR WPI; 2020-439384/045.
XX
CC PT New bispecific antibody comprising first binding site specifically
CC PT binding to programmed cell death-ligand 1 and second binding specifically
CC PT binding to glucocorticoid-Induced TNF receptor-related, useful for e.g.
CC PT treat cancer.
XX
CC PS Example 7; SEQ ID NO 61; 127pp; English.
XX
CC The present invention relates to a novel bispecific antibody having one
CC arm binding to a cancer associated antigen on a cancer cell, such as CD33
CC (Siglec-3), EGFR or PD-L1 (CD274), and a second arm binding to a
CC costimulatory molecule, such as GITR (TNFRSF18/CD357), 0X40
CC (TNFRSF4/CD134), CD40 (TNFRSF5), ICOS (CD278) or 4-1BB (CD137 and
CC TNFRSF9). Bridging by the bispecific antibody between cancer cells
CC expressing the cancer associated antigen and immune cells expressing the
CC costimulatory molecule results in clustering of the costimulatory
CC molecules and selective activation of the immune cells at a location
CC proximate to the cancer cells. Thus, the immune cells can exert an
CC immunotherapeutic effect against the cancer cells with reduced toxicity
CC to healthy tissue. The invention further discloses: (1) a monoclonal
CC antibody specifically binding to PD-L1 comprising a mature heavy chain
CC variable (VH) region comprising complementarity determining regions
CC (CDRs) CDRH1, CDR2H2 and CDRH3 of SEQ ID NOs:62-64 (see BHU89179-
CC BHU89181), SEQ ID NOs:75-77 (see BHU89192-BHU89194), or SEQ ID NOs:85-87
CC (see BHU89202-BHU89204) respectively and a mature light chain variable VL
CC region comprising complementarity determining region (CDRs) CDRL1, CDRL2
CC and CDRL3 of SEQ ID NOs:66-68 (see BHU89183-BHU89185), or SEQ ID NOs:79-
CC 81 (see BHU89196-BHU89198) or SEQ ID NOs:89-91 (see BHU89206-BHU89208)
CC respectively; (2) a pharmaceutical composition comprising the bispecific
CC antibody or the monoclonal antibody and a pharmaceutically acceptable
CC carrier; (3) a method for treating or effecting prophylaxis of cancer,
CC which involves administering an effective regime of the bispecific
CC antibody or the monoclonal antibody to a subject having or at risk of
CC cancer; and (4) a method for treating infection, which involves
CC administering an effective regime of the bispecific antibody or the
CC monoclonal antibody to a subject having or at risk of infection. The
CC novel bispecific antibody of the invention is useful for treating or
CC preventing cancer and infection. Note: A fragment of the present sequence
CC corresponding to residues 20-138 (see BHU89263) is specifically claimed
CC in Claim 5.
XX
SQ Sequence 138 AA;
Query Match 83.0%; Score 154.4; Length 138;
Best Local Similarity 39.7%;
Matches 31; Conservative 0; Mismatches 1; Indels 46; Gaps 2;
Qy 1 SSYIS--------------WIYAGTGGTSYNQKFTG------------------------ 22
||||| |||||||||||||||||
Db 50 SSYISWVRQAPGQGLEWIAWIYAGTGGTSYNQKFTGRATITVDESTSTAYMELSSLRSED 109
Qy 23 --------HEGKYWYFDV 32
||| ||||||
Db 110 TAVYYCARHEGVYWYFDV 127
Alignment with SEQ ID NO: 29 – 31
BHU89182
ID BHU89182 standard; protein; 127 AA.
XX
AC BHU89182;
XX
DT 09-JUL-2020 (first entry)
XX
DE Anti-PD-L1 humanizied antibody light chain variable region, SEQ:65.
XX
KW CD274; PD-L1 protein; Programmed cell death ligand 1;
KW antibody engineering; antibody therapy; antimicrobial-gen.; cancer;
KW cytostatic; humanizied antibody; infectious disease;
KW light chain variable region; prophylactic to disease; therapeutic.
XX
OS Mus sp.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..22
FT /label= Signal_peptide
FT Protein 23..127
FT /label= Mature_protein
FT /note= "Specifically claimed in claim 5"
XX
CC PN WO2020102233-A1.
XX
CC PD 22-MAY-2020.
XX
CC PF 12-NOV-2019; 2019WO-US060982.
XX
PR 13-NOV-2018; 2018US-0760328P.
PR 25-APR-2019; 2019US-0838579P.
XX
CC PA (JNBI-) JN BIOSCIENCES LLC.
XX
CC PI Tsurushita N, Tso JY;
XX
DR WPI; 2020-439384/045.
XX
CC PT New bispecific antibody comprising first binding site specifically
CC PT binding to programmed cell death-ligand 1 and second binding specifically
CC PT binding to glucocorticoid-Induced TNF receptor-related, useful for e.g.
CC PT treat cancer.
XX
CC PS Example 7; SEQ ID NO 65; 127pp; English.
XX
CC The present invention relates to a novel bispecific antibody having one
CC arm binding to a cancer associated antigen on a cancer cell, such as CD33
CC (Siglec-3), EGFR or PD-L1 (CD274), and a second arm binding to a
CC costimulatory molecule, such as GITR (TNFRSF18/CD357), 0X40
CC (TNFRSF4/CD134), CD40 (TNFRSF5), ICOS (CD278) or 4-1BB (CD137 and
CC TNFRSF9). Bridging by the bispecific antibody between cancer cells
CC expressing the cancer associated antigen and immune cells expressing the
CC costimulatory molecule results in clustering of the costimulatory
CC molecules and selective activation of the immune cells at a location
CC proximate to the cancer cells. Thus, the immune cells can exert an
CC immunotherapeutic effect against the cancer cells with reduced toxicity
CC to healthy tissue. The invention further discloses: (1) a monoclonal
CC antibody specifically binding to PD-L1 comprising a mature heavy chain
CC variable (VH) region comprising complementarity determining regions
CC (CDRs) CDRH1, CDR2H2 and CDRH3 of SEQ ID NOs:62-64 (see BHU89179-
CC BHU89181), SEQ ID NOs:75-77 (see BHU89192-BHU89194), or SEQ ID NOs:85-87
CC (see BHU89202-BHU89204) respectively and a mature light chain variable VL
CC region comprising complementarity determining region (CDRs) CDRL1, CDRL2
CC and CDRL3 of SEQ ID NOs:66-68 (see BHU89183-BHU89185), or SEQ ID NOs:79-
CC 81 (see BHU89196-BHU89198) or SEQ ID NOs:89-91 (see BHU89206-BHU89208)
CC respectively; (2) a pharmaceutical composition comprising the bispecific
CC antibody or the monoclonal antibody and a pharmaceutically acceptable
CC carrier; (3) a method for treating or effecting prophylaxis of cancer,
CC which involves administering an effective regime of the bispecific
CC antibody or the monoclonal antibody to a subject having or at risk of
CC cancer; and (4) a method for treating infection, which involves
CC administering an effective regime of the bispecific antibody or the
CC monoclonal antibody to a subject having or at risk of infection. The
CC novel bispecific antibody of the invention is useful for treating or
CC preventing cancer and infection. Note: A fragment of the present sequence
CC corresponding to residues 23-127 (see BHU89265) is specifically claimed
CC in Claim 5.
XX
SQ Sequence 127 AA;
Query Match 79.6%; Score 108.3; Length 127;
Best Local Similarity 34.2%;
Matches 25; Conservative 1; Mismatches 0; Indels 47; Gaps 2;
Qy 1 SASSSVSYVH---------------DTSNLAS---------------------------- 17
||||||||:| |||||||
Db 45 SASSSVSYMHWYQQKPGQAPRPWIYDTSNLASGFPARFSGSGSGTDFTLTISSLEPEDFA 104
Qy 18 ----HQRSSYPWT 26
|||||||||
Db 105 VYYCHQRSSYPWT 117
Alignment with SEQ ID NO: 135
BHU89178
ID BHU89178 standard; protein; 138 AA.
XX
AC BHU89178;
XX
DT 09-JUL-2020 (first entry)
XX
DE Anti-PD-L1 humanizied antibody heavy chain variable region, SEQ:61.
XX
KW CD274; PD-L1 protein; Programmed cell death ligand 1;
KW antibody engineering; antibody therapy; antimicrobial-gen.; cancer;
KW cytostatic; heavy chain variable region; humanizied antibody;
KW infectious disease; prophylactic to disease; therapeutic.
XX
OS Mus sp.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..19
FT /label= Signal_peptide
FT Protein 21..138
FT /label= Mature_protein
FT /note= "Specifically claimed in claim 5"
XX
CC PN WO2020102233-A1.
XX
CC PD 22-MAY-2020.
XX
CC PF 12-NOV-2019; 2019WO-US060982.
XX
PR 13-NOV-2018; 2018US-0760328P.
PR 25-APR-2019; 2019US-0838579P.
XX
CC PA (JNBI-) JN BIOSCIENCES LLC.
XX
CC PI Tsurushita N, Tso JY;
XX
DR WPI; 2020-439384/045.
XX
CC PT New bispecific antibody comprising first binding site specifically
CC PT binding to programmed cell death-ligand 1 and second binding specifically
CC PT binding to glucocorticoid-Induced TNF receptor-related, useful for e.g.
CC PT treat cancer.
XX
CC PS Example 7; SEQ ID NO 61; 127pp; English.
XX
CC The present invention relates to a novel bispecific antibody having one
CC arm binding to a cancer associated antigen on a cancer cell, such as CD33
CC (Siglec-3), EGFR or PD-L1 (CD274), and a second arm binding to a
CC costimulatory molecule, such as GITR (TNFRSF18/CD357), 0X40
CC (TNFRSF4/CD134), CD40 (TNFRSF5), ICOS (CD278) or 4-1BB (CD137 and
CC TNFRSF9). Bridging by the bispecific antibody between cancer cells
CC expressing the cancer associated antigen and immune cells expressing the
CC costimulatory molecule results in clustering of the costimulatory
CC molecules and selective activation of the immune cells at a location
CC proximate to the cancer cells. Thus, the immune cells can exert an
CC immunotherapeutic effect against the cancer cells with reduced toxicity
CC to healthy tissue. The invention further discloses: (1) a monoclonal
CC antibody specifically binding to PD-L1 comprising a mature heavy chain
CC variable (VH) region comprising complementarity determining regions
CC (CDRs) CDRH1, CDR2H2 and CDRH3 of SEQ ID NOs:62-64 (see BHU89179-
CC BHU89181), SEQ ID NOs:75-77 (see BHU89192-BHU89194), or SEQ ID NOs:85-87
CC (see BHU89202-BHU89204) respectively and a mature light chain variable VL
CC region comprising complementarity determining region (CDRs) CDRL1, CDRL2
CC and CDRL3 of SEQ ID NOs:66-68 (see BHU89183-BHU89185), or SEQ ID NOs:79-
CC 81 (see BHU89196-BHU89198) or SEQ ID NOs:89-91 (see BHU89206-BHU89208)
CC respectively; (2) a pharmaceutical composition comprising the bispecific
CC antibody or the monoclonal antibody and a pharmaceutically acceptable
CC carrier; (3) a method for treating or effecting prophylaxis of cancer,
CC which involves administering an effective regime of the bispecific
CC antibody or the monoclonal antibody to a subject having or at risk of
CC cancer; and (4) a method for treating infection, which involves
CC administering an effective regime of the bispecific antibody or the
CC monoclonal antibody to a subject having or at risk of infection. The
CC novel bispecific antibody of the invention is useful for treating or
CC preventing cancer and infection. Note: A fragment of the present sequence
CC corresponding to residues 20-138 (see BHU89263) is specifically claimed
CC in Claim 5.
XX
SQ Sequence 138 AA;
Query Match 93.6%; Score 596; Length 138;
Best Local Similarity 94.1%;
Matches 112; Conservative 1; Mismatches 6; Indels 0; Gaps 0;
Qy 1 QGQLVQSGAEVKKPGSSVKVSCKTSGFTFSSSYISWVRQAPGQGLEWMGWIYAGTGGTSY 60
| ||||||||||||||||||||| |||||||||||||||||||||||: |||||||||||
Db 20 QVQLVQSGAEVKKPGSSVKVSCKASGFTFSSSYISWVRQAPGQGLEWIAWIYAGTGGTSY 79
Qy 61 NQKFTGRVTITVDTSTSTAYMELSSLRSEDTAVYYCARHEGKYWYFDVWGQGTTVTVSS 119
||||||| ||||| ||||||||||||||||||||||||||| |||||||||||||||||
Db 80 NQKFTGRATITVDESTSTAYMELSSLRSEDTAVYYCARHEGVYWYFDVWGQGTTVTVSS 138
Alignment with SEQ ID NO: 144
BHU89182
ID BHU89182 standard; protein; 127 AA.
XX
AC BHU89182;
XX
DT 09-JUL-2020 (first entry)
XX
DE Anti-PD-L1 humanizied antibody light chain variable region, SEQ:65.
XX
KW CD274; PD-L1 protein; Programmed cell death ligand 1;
KW antibody engineering; antibody therapy; antimicrobial-gen.; cancer;
KW cytostatic; humanizied antibody; infectious disease;
KW light chain variable region; prophylactic to disease; therapeutic.
XX
OS Mus sp.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..22
FT /label= Signal_peptide
FT Protein 23..127
FT /label= Mature_protein
FT /note= "Specifically claimed in claim 5"
XX
CC PN WO2020102233-A1.
XX
CC PD 22-MAY-2020.
XX
CC PF 12-NOV-2019; 2019WO-US060982.
XX
PR 13-NOV-2018; 2018US-0760328P.
PR 25-APR-2019; 2019US-0838579P.
XX
CC PA (JNBI-) JN BIOSCIENCES LLC.
XX
CC PI Tsurushita N, Tso JY;
XX
DR WPI; 2020-439384/045.
XX
CC PT New bispecific antibody comprising first binding site specifically
CC PT binding to programmed cell death-ligand 1 and second binding specifically
CC PT binding to glucocorticoid-Induced TNF receptor-related, useful for e.g.
CC PT treat cancer.
XX
CC PS Example 7; SEQ ID NO 65; 127pp; English.
XX
CC The present invention relates to a novel bispecific antibody having one
CC arm binding to a cancer associated antigen on a cancer cell, such as CD33
CC (Siglec-3), EGFR or PD-L1 (CD274), and a second arm binding to a
CC costimulatory molecule, such as GITR (TNFRSF18/CD357), 0X40
CC (TNFRSF4/CD134), CD40 (TNFRSF5), ICOS (CD278) or 4-1BB (CD137 and
CC TNFRSF9). Bridging by the bispecific antibody between cancer cells
CC expressing the cancer associated antigen and immune cells expressing the
CC costimulatory molecule results in clustering of the costimulatory
CC molecules and selective activation of the immune cells at a location
CC proximate to the cancer cells. Thus, the immune cells can exert an
CC immunotherapeutic effect against the cancer cells with reduced toxicity
CC to healthy tissue. The invention further discloses: (1) a monoclonal
CC antibody specifically binding to PD-L1 comprising a mature heavy chain
CC variable (VH) region comprising complementarity determining regions
CC (CDRs) CDRH1, CDR2H2 and CDRH3 of SEQ ID NOs:62-64 (see BHU89179-
CC BHU89181), SEQ ID NOs:75-77 (see BHU89192-BHU89194), or SEQ ID NOs:85-87
CC (see BHU89202-BHU89204) respectively and a mature light chain variable VL
CC region comprising complementarity determining region (CDRs) CDRL1, CDRL2
CC and CDRL3 of SEQ ID NOs:66-68 (see BHU89183-BHU89185), or SEQ ID NOs:79-
CC 81 (see BHU89196-BHU89198) or SEQ ID NOs:89-91 (see BHU89206-BHU89208)
CC respectively; (2) a pharmaceutical composition comprising the bispecific
CC antibody or the monoclonal antibody and a pharmaceutically acceptable
CC carrier; (3) a method for treating or effecting prophylaxis of cancer,
CC which involves administering an effective regime of the bispecific
CC antibody or the monoclonal antibody to a subject having or at risk of
CC cancer; and (4) a method for treating infection, which involves
CC administering an effective regime of the bispecific antibody or the
CC monoclonal antibody to a subject having or at risk of infection. The
CC novel bispecific antibody of the invention is useful for treating or
CC preventing cancer and infection. Note: A fragment of the present sequence
CC corresponding to residues 23-127 (see BHU89265) is specifically claimed
CC in Claim 5.
XX
SQ Sequence 127 AA;
Query Match 94.7%; Score 533; Length 127;
Best Local Similarity 92.5%;
Matches 98; Conservative 6; Mismatches 2; Indels 0; Gaps 0;
Qy 1 EIVMTQSPATLSVSPGERATLSCSASSSVSYVHWYQQKPGQAPRPWIYDTSNLASGFPAR 60
|||:||||||||:||||||||||||||||||:||||||||||||||||||||||||||||
Db 22 EIVLTQSPATLSLSPGERATLSCSASSSVSYMHWYQQKPGQAPRPWIYDTSNLASGFPAR 81
Qy 61 FSGSGSGTEYTLTISSLQSEDAAVYYCHQRSSYPWTFGGGTKVEIK 106
||||||||::|||||||: || ||||||||||||||||||||||||
Db 82 FSGSGSGTDFTLTISSLEPEDFAVYYCHQRSSYPWTFGGGTKVEIK 127
Prosecution Insights