Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant’s election with traverse of Group 1, claims 118-124, 136 and 137 in the reply filed on March 10, 2026 is acknowledged.
Applicant’s election species: 1) Fab as the second binding site; 2) claim 124 option (a) as the specific configuration; is also acknowledged. It is noted that in view of amendments of claim 123, the election requests for the first epitope and the second epitope are not applicable.
Applicants traversed the restriction on the ground that Liu et al. does not teach a second component comprising a Fc, a second antigen binding site comprising a Fab or a second VHH that specifically binds to a second epitope, and one or more additional VHH(s) as defined by the amended claim 118. The traversal is not found to be persuasive because prior art still teaches the amended claim 118. For example, Zhang (Zhang et al., US 2020/0369770 A1, Publication Date: 11/26/2020) teaches various multispecific antibody comprising VHH domains and Fc domain (see Figs. 1-8). The antibody of Fig. 5 would read on the antigen binding protein of instant claim 118 (see 102 and 103 rejections below).
Therefore, the technical feature linking the inventions of Groups I-IV does not constitute a special technical feature as defined by PCT Rule 13.2 as it does not define a contribution over the prior art.
Regarding Applicant' s arguments about search and examination burden, the instant application is a National Stage application filed under 35 U.S.C. §371 and the restriction of the various groups is determined with respect to unity of invention as covered in Chapter 1800 of the MPEP. See MPEP 801. Burden of search is not the criteria for proper restriction under 37 C.F.R. 1.475, PCT article 17(3) (a), and 37 C.F.R 1.476 (c). Thus, Applicant' s arguments are not found persuasive. Nevertheless, the inventions have acquired a separate status in the art in view of their different classification, the inventions require a different field of search, and the inventions may raise different non-prior art issues such as under 35 U.S.C. 112, first paragraph. Thus, the requirement is still deemed proper and is therefore made FINAL.
Claims 119-122 and 125-132 were canceled.
Claims 118, 123 and 124 are amended.
Claims 118, 123, 124 and 133-143 are pending.
Claims 133-135 and 138-143 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 118, 123, 124, 136 and 137 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 application of International Patent Application No. PCT/CN2021/142655 filed December 29, 2021, which claims the benefit of priority to International Patent Application No. PCT/CN2020/141675 filed December 30, 2020.
Certified copies of foreign priority applications have been received as required by 37 CFR 1.55. The priority date has been established as December 30, 2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 06/28/2023, 01/31/2025 and 01/21/2026 have been considered and entered by examiner.
Claim Objections
Claim 124 is objected to because of the following informalities: a conjunction “or” should be inserted between option (c) and option (d). Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 123 are 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 123 recites the limitation "the VHH(s)" in line 1 which renders the claim indefinite. Claim 123 depends on claim 118 which recites: “a first VHH”, “a second VHH” and “one or more additional VHHs”. It is unclear which VHH the “the VHH(s)” refers to.
Claim 123 recites “one or more of a cancer associated antigen, a cancer specific antigen and an immune checkpoint molecule including the following antigens: VEGF, Ang-2,…OX40, GITR, and CD40”. It is unclear whether “a cancer associated antigen, a cancer specific antigen and an immune checkpoint molecule” is limited within the proteins listed in the claim. Amending claim 123 as “one or more of a cancer associated antigen, a cancer specific antigen and an immune checkpoint molecule selected from the group consisting: VEGF, Ang-2,…OX40, GITR, and CD40” would overcome the rejection.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 124 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 124 (b) recites a specific configuration of the antigen binding protein of claim 118 as follow: (1) VHH1-CH1-Fc; (2) VHH-CL. However, claim 18 defines the antigen binding protein as follow: (1)VHH; (2) Fc-Fab-VHH or Fc-VHH-VHH(s). Thus, claim 124(b) fails to include all the limitations of claim 118.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
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 118, 123, 124, 136 and 137 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. This is a WRITTEN DESCRIPTION rejection.
The claims encompass a broad genus of antigen binding proteins comprising unlimited VHH(s). Given Broadest Reasonable Interpretation (BRI), the claims would encompass a broad genus of VHHs to all possible antigens. The specification discloses only a few VHHs to only a few antigens (e.g. VEGF, Ang-2, MSLN …, see Examples of the instant publication US 2024/0076411 A1). The specification does not disclose other VHHs, to any other antigens which are encompassed by the claims. Therefore, the specification does not provide sufficient representative examples or adequate description for the entire genus of VHHs as broadly claimed. The specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed".
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
In the instant case, the claim encompasses a broad genus of VHHs which can be any sequences to any antigens. By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope. Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract). Although nanobodies lacking light chains are small antibody fragments derived from heavy-chain-only antibodies and only have three CDR loops. These three CDRs that make up the binding surface which can be considered synonymous with the paratope of conventional antibodies (see page 237, the bridging paragraph of cols. 1-2 of Salamouni et al., FEBS Open Bio. 15 (2025), 236-253). In addition, mutations disrupting CDR-H3 and the framework residues results in significant loss of affinity and stability (see page 241, col. 1) of Salamouni. Thus, the specific VHH antibodies disclosed by the specification would not tell structure of other VHH antibody to the same or different antigens.
In addition, the instant specification has not provided a sufficient description about the correlation between the recited functions and the structure of the VHH antibody. Based on the Specification and prior art, one of ordinary skilled in the art would not be able to “visualize or recognize” the encompassed VHHs. Logically, the specification lacks written description for the claimed antigen-binding proteins.
Although Applicants may argue that it is possible to screen for each VHH and to make the antigen binding protein, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. "As we held in Lilly, "[a]n adequate written description of a DNA ... 'requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention." 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171 ). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions." Knowledge of screening methods provides no information about the structure of any future VHH antibodies yet to be discovered that may function as claimed.
Taken together, the instant specification has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between functions and the structure of the antigen binding protein by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of antigen binding proteins broadly encompassed by the claims.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 118, 123, 124 and 137 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Zhang (Zhang et al., US 2020/0369770 A1, Publication Date: 11/26/2020).
Zhang teaches that single domain antibodies (sdAbs, same as VHH as evidenced by instant claim 118) can bind antigens with similar affinity and specificity as mAbs and can be used as building blocks to create IgG-like antibodies ([0007]).
Zhang teaches multispecific antigen binding proteins comprising sdAb domain (Figs. 1-8, and claims 1, 5, and 6).
Fig. 5 and paragraph [0028] of Zhang teaches depicts a schematic structure of an exemplary trispecific antigen binding protein (TABP) comprising a monospecific full-length antibody having two identical heavy chains and two identical light chains, a first sdAb and a second sdAb, wherein the C-terminus of the first sdAb is fused to the N-terminus of the heavy chain via a first optional peptide linker and the N-terminus of the second sdAb is fused to the C-terminus of the light chain via a second optional peptide linker. The full-length antibody has two antigen binding sites that specifically bind the first epitope. The first sdAb specifically binds the second epitope. The second sdAb specially binds to the third epitope. For example, the TABP can consist of four polypeptide chains with structures from the N-terminus to the C-terminus as follows:
(1) VL-CL-VHH2;
(2) VHH1-VH-CH1-CH2-CH3 (this reads on the first polypeptide of claim 124(a));
(3) VHH1-VH-CH1-CH2-CH3 (this reads on the second polypeptide of claim 124(a)); and
(4) VL-CL-VHH2 (this read on the third polypeptide of claim 124(a)).
As shown by Fig. 5, the VH and VL (a Fab, the elected species) can bind to an epitope and VL and CH1 domain are associated with each other to form an IgG structure. Thus, the trispecific antibody of Fig. 5 reads on the configuration of claim 124 (a) (the elected species).
Zhang teaches the first, second and/or third epitope can be PD-1, OX40, GITR ([0013]), Ang-2, or VEGF ([0016]). Also see claims 17-23.
Regarding claim 123, Zhang teaches TPTL15 of format Fig. 5: the first polypeptide comprises from the N-terminus to the C terminus: the anti-TIGIT VHH, a peptide linker, and a heavy chain of the anti-PD-1 antibody; and the second polypeptide comprises from the N-terminus to the C terminus: a light chain of the anti-PD-1 antibody, a peptide linker, and the anti-LAG-3 VHH ([0356]). Thus, the VHHs of TPTL15 specifically bind to LAG-3 and TIGIT; the Fab of TPTL15 specifically bind to PD-1.
Regarding claim 137, Zhang teaches pharmaceutical composition comprising the multispecific antigen binding protein and a pharmaceutically acceptable carrier ([0220] and claim 54).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 136 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Zhang et al., US 2020/0369770 A1, Publication Date: 11/26/2020) as applied to claims 118, 123, 124 and 137 above, and further in view of Shim (Shim, Biomolecules, 2020, 10, 360, Publication Date: 02/26/2020).
Zhang teaches the antigen binding protein of claim 118 as set forth above. Zhang further teaches the antibody can be conjugated with one or more cytotoxic agents in order to generate an immunoconjugate ([0310]). However, Zhang dose not explicitly teach that the antigen binding protein covalently bound to a therapeutic agent.
Shim teaches that in order to overcome the limitations of therapeutic antibodies and enhance their efficacy, various engineering and modification approaches have been devised and applied to the conventional immunoglobulin molecular format, e.g. antibody–drug conjugate (ADC) formats (the bottom paragraph of page 1).
Shim teaches that antibody–drug conjugates (ADCs) are another class of highly potent antibody-based therapeutics. ADCs consist of three integral components: (1) an antibody targeting cancer cell-specific antigen, (2) a cytotoxic payload, and (3) a chemical linker that connects the drug and the antibody (covalently bound through the linker).
Shim teaches various cytotoxic drugs and linkers which can be used for ADCs (§ 3.2. Cytotoxic Drugs; and § 3.3. Linkers).
Shim teaches various formats in which a drug can be covalently bound to the Fc region of an antibody (Fig. 3).
Shim teaches the methods of making ADC (§ 3.4. Conjugation of Linker-Payload to Antibody).
Shim teaches specific antibody-drug conjugates (page 21, para. 2).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of Zhang and Shim and to modify the antigen-binding protein of Zhang by making an antibody-drug conjugate (drug covalently bound to Fc region of antibody) as taught by Shim. Given the teachings of Zhang and Shim, one of ordinary skilled in the art would have had expected that the ADC would had a better therapeutic activity than the antigen-binding protein alone. Because the method of making ADC are well known in the art, as evidenced by Shim, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to make a better therapeutic agent.
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 118, 123, 124, 136 and 137 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 7-11, 13-17, 20-23, 26 and 27 of copending Application No. 17/792,386 (hereinafter Appl. 386) in view of Zhang (Zhang et al., US 2020/0369770 A1, Publication Date: 11/26/2020) and Shim (Shim, Biomolecules, 2020, 10, 360, Publication Date: 02/26/2020).
This is a provisional nonstatutory double patenting rejection.
Claim 1 of Appl. 386 teaches a bispecific antibody or antigen-binding portion thereof, comprising a PD- L1 antigen-binding moiety associated with a VEGF antigen-binding moiety, wherein: the PD-L1 antigen-binding moiety comprises: a complementarity determining region (CDR) 1 comprising SEQ ID NO: 1, a CDR2 comprising SEQ ID NO: 2, and a CDR3 comprising SEQ ID NO: 3; and the VEGF antigen-binding moiety comprises: a heavy chain complementarity determining region (HCDR) 1 comprising SEQ ID NO: 4, a HCDR2 comprising SEQ ID NO: 5, a HCDR3 comprising SEQ ID NO: 6, a light chain complementarity determining region (LCDR) 1 comprising SEQ ID NO: 7, a LCDR2 comprising SEQ ID NO: 8, and a LCDR3 comprising SEQ ID NO: 9, wherein the PD-L1 antigen-binding moiety is operably linked to the N terminal of the light chain of the VEGF antigen-binding moiety.
Claim 3 of Appl. 386 teaches The bispecific antibody or antigen-binding portion thereof of claim 1,wherein the VEGF antigen-binding moiety comprises: a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 11 or an amino acid sequence at least 85%, 90%, or 95% identical to SEQ ID NO: 11; and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence at least 85%, 90%, or 95% identical to SEQ ID NO: 12.
Claim 5 of Appl. 386 teaches that the bispecific antibody or antigen-binding portion thereof of claim 1, wherein the PD-L1 antigen-binding moiety is from a VHH antibody derived from a camelid animal, comprising an alpaca or a llama.
Claim 9 of Appl. 386 teaches the bispecific antibody or antigen-binding portion thereof of claim 1, comprising a heavy chain and a light chain, wherein: the heavy chain comprises domains operably linked as VH-CH1-hinge-Fc, wherein the VH-CH1 is from the VEGF antigen binding moiety; and the light chain comprises domains operably linked as VHH-VL-CL, wherein the VHH is from the PD-L1 antigen binding moiety and the VL-CL is from the VEGF antigen binding moiety.
Claim 10 of Appl. 386 teaches the bispecific antibody or antigen-binding portion thereof of claim 9, wherein the Fc region is a human IgG Fc region, preferably including a human IgG1 Fc region.
Claim 16 of Appl. 386 teaches a pharmaceutical composition comprising the bispecific antibody or the antigen-binding portion thereof of claim 1 and a pharmaceutically acceptable carrier.
Taken together, the claims of Appl. 386 teach a bispecific antibody comprising a VHH specifically binding to PD-L1, a Fab specifically binding to VEGF, and a Fc. However, the claims of Appl. 386 don’t teach the configurations and ADC as instantly claimed. Zhang and Shim’s teachings are described above. In particular, Zhang teaches various formats of VHH and Fc containing antibody fusion protein. Shim teaches advantages of ADC and methods of making ADC.
Regarding claims 118, 123 and 124, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to relate the teachings of combine the teachings of the claims of Appl. 386 and Zhang and to try with different configurations (e.g. configurations shown in Figs 1-8 of Zhang) taught by Zhang to connect the PD-L1 binding moiety and VEGF binding moiety. The motivation would have been to expand the options, to modify valences of each binding moiety and to target multiple antigens for better therapeutic properties. Given the methods of making multispecific antibodies are well known in the art (as evidenced by Zhang), one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention.
Regarding claim 136, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 386, Zhang and Shim and to modify the antigen-binding protein by making an antibody-drug conjugate (drug covalently bound to Fc region of antibody) as taught by Shim. Given the teachings of Zhang and Shim, one of ordinary skilled in the art would have had expected that the ADC would had a better therapeutic activity than the antigen-binding protein alone. Because the method of making ADC are well known in the art, as evidenced by Shim, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to make a better therapeutic agent.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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