DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
The Response to the Election of Species Requirement mailed on November 14, 2025 has been entered. Applicant elects without traverse an antigen-binding polypeptide complex comprising a first polypeptide having the structure of “VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc” and a second polypeptide having the structure of “VL2-L9-VL4-L10-VH4-L11-VH3-L12-Fc” in the reply filed March 10, 2026. Applicant further elects the corresponding CDR amino acid sequences as reproduced below (see Remarks at page 9):
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Applicant submits that claims 76-87 read on the elected species.
The claims filed March 10, 2026 are acknowledged. Claims 1-75 are canceled. Claims 76-87 are newly added. Claims 76-87 are pending and under examination herein.
Information Disclosure Statements
The Information Disclosure Statements filed on October 3, 2023, September 25, 2024, September 18, 2025, and March 10, 2026 have been considered.
It is noted for Applicant that an updated version of the Information Disclosure Statement (IDS) form can be found at https://www.uspto.gov/patents/apply/forms. The version of the Information Disclosure Statements submitted in September 2024, September 2025, and March 2026 is approved for use through May 31, 2024.
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 76-78, 82, and 84-87 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991).
MPEP § 2163 states that 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, or it may be satisfied by the 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. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
The claimed invention. The nature and scope of the claimed invention at issue is the antigen-binding polypeptide complex of claim 76, which comprises variable regions of VL1, VL2, VL3, VH1, VH2, and VH3, which generically bind to any “tumor-associated antigen” (TAA). With the exception of claims 79-81 and 83 (which are not included in this rejection), claim 76 and its dependent claims do not require that corresponding pairs of VH/VL domains (e.g., VH1/VL1, VH2/VL2, VH3/VL3) bind to the same antigen so long as they bind to a TAA. Claim 78 further allows that binding of the VL1, VL2, VL3, VH1, VH2, and VH3 domains is “mixed and matched” among the tumor-associated antigens of c-Met, CD28, and TROP2. By way of example, the VL1 domain may specifically bind to c-Met while the VH1 domain binds to CD28, and/or the VL2 domain may specifically bind to TROP2 while the VH2 domain specifically binds to c-Met. The rejected claims fail to satisfy the written description requirement because neither Applicant's disclosure nor the prior art support the notion that random combinations of VH/VL domains against mismatched antigens would be expected to yield a protein having a functional antigen-binding site that performs the required function of specifically binding to either one or both of said antigens.
State of the prior art. It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro (Frontiers in Immunology (2018) 8: 1751), “The IgG Molecule” (page 3) and Figure 1. Sela-Culang (Frontiers in Immunology (2013) 4: 302) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3). Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Ni (The Protein Journal (2024) 43: 683-696) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction).
Exemplary multispecific antibodies that bind to CD3 and cMet, CD28, and/or TROP2 are known in the art. Consider, for example, Chiu (U.S. Patent No. 11,149,094; cited in IDS); Bonvini (U.S. Patent No. 10,633,440; cited in IDS); Yang (US 2017/0320967 A1; cited in IDS); Chang (U.S. Patent No. 9,382,329; cited in IDS); and Lowman (US 2015/0079088 A1; cited in IDS).
Scope of species disclosed in original specification. The disclosure illustrates exemplary non-masked tetraspecific constructs comprising VH/VL pairs having specificity for CD3, CD28, TROP2, and c-Met, including:
MX445, MX446, MX447, and MX448 (e.g., Figures 7 and 11-16; Examples 9-14);
MX612 and MX613 (e.g., Figures 9-10, 12-16; Examples 7-8 and 10-14); and
MX974, MX975, and MX976 (e.g., Figures 18-19; Examples 15-16).
It is not apparent from the working examples and figures the exact order of the VH and VL domains in the first and second polypeptide chains of each of these exemplary constructs (i.e., whether the first and second polypeptides have the structures elected by Applicant in the Response to the Election of Species Requirement or an alternative configuration). However, it is evident that these constructs comprise specific pairs of VH and VL domains that complex with one another to specifically bind to one distinct antigen (i.e., one of CD3, CD28, TROP2, or c-Met), which are not “mixed and matched”.
MPEP § 2163 states that 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. While the disclosure does enumerate several exemplary embodiments wherein the VH1, VH2, VH3, VL1, VL2, and VL3 correspond to one of CD28, TROP2, or c-Met, these constructs are all tetraspecific and the corresponding VH and VL within each pair (e.g., VH1/VL1, VH2/VL2, VH3/VL3) specifically bind to the same respective antigen.
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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. Based on the disclosure, Applicant is not in possession of antigen binding polypeptide complexes in which members of each respective VH/VL pairing bind to separate antigens, nor does Applicant provide a showing that such pairings would yield a functional protein that specifically binds to either antigen as claimed.
Conclusion. For all of the reasons presented above, one of skill in the art would not know which of the countless other antigen-binding polypeptide complexes encompassed by the highly general structural requirements of the claims would also possess the required functional activity. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess the full genus of antigen-binding polypeptide complexes as broadly claimed at the time the application was filed.
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.
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.
(1)
Claims 76-78, 84-85, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Alt (FEBS Letters (1999) 454: 90-94) in view of Y. Liu (WO 2021/035096 A1; published February 25, 2021).
Alt teaches that bispecific IgG molecules have been implemented successfully for antibody-mediated immunotherapy of tumors (e.g., Introduction). Although Fc-mediated effector functions and long serum half-life are essential for many therapeutic applications, Alt notes antibodies lacking constant regions “lack the associated effector functions and are rapidly cleared from serum due to their small size” (Introduction). Pertinent to claim 76, Alt describes bispecific, tetravalent IgG-like antibody molecules combining single-chain diabodies (scDb) with an IgG1 Fc or CH3 region (scDb-Fc or scDb-CH3, respectively), which are illustrated in Figure 1. The variable domains in the polypeptide chains of the sdDb-Fc/CH3 constructs comprise a (G4S) linker between the first and second variable domains and between the third and fourth variable domains in each polypeptide chain, while a 15-amino acid linker joins the second and third variable domains of each construct (e.g., Figure 1). Alt teaches that the fusion of the scDb to Fc produces dimeric fusion proteins “exhibiting four functional antigen binding sites with increased functional activity” (Abstract), as demonstrated by the scDb-Fc constructs showing higher antigen binding and enzyme recruitment activities (e.g., Figures 3 and 5-6; Results, pages 92-93).
However, Alt does not expressly teach scDb-Fc constructs wherein the structural order of the first and second polypeptide chains is VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc and VL3-L9-VL4-L10-VH4-L11-VH3-L12-Fc, respectively. Alt also does not teach that VH1, VH2, VH3, VL1, VL2, and VL3 each bind to a tumor-associated antigen and that VH4 and VL4 bind to CD3.
Y. Liu discloses polypeptides comprising a multivalent (e.g., tetravalent) antigen-binding unit directed to cellular targets and methods of use thereof in treating cancer, wherein said antigen-binding units may comprise an antigen-binding domain that exhibits specific binding to CD3 and an antigen-binding domain that exhibits specific binding to a tumor-associated antigen, e.g., CD28, or TROP2, or HGFR (also called c-Met), among others (e.g., Abstract; ¶ 0005-0013, 00209-00220). Y. Liu discloses that bivalent antigen-binding units of the invention may comprise two scFvs each comprising one VH and one VL region (e.g., a diabody), having four domains arranged in the format of VL1-Lx-VL2-Ly-VH2-Lz-VH1, where Lx, Ly, and Lz are peptide linkers that may be the same or different (e.g., ¶ 00150-00152), relevant to claims 76-78 and 84. Y. Liu also provides for pharmaceutical compositions comprising the antigen-binding units of the invention and methods of administering said antigen-binding units in a cancer treatment method (e.g., ¶ 00324-00326; claim 1), relevant to claims 85 and 87.
In view of the above, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to generate a tetravalent scDb-Fc construct (such as that illustrated by Alt) wherein the antigen-binding domains bind to CD3 and one or more of CD28, c-Met, or TROP2 and wherein the antigen-binding domains are arranged in a VL-VL-VH-VH configuration (based on the further teachings of Y. Liu). The skilled artisan would have been motivated to do so because Alt teaches that scDb-Fc constructs demonstrate increased functional affinity for antigen(s) while also having longer half-life and Fc-mediated effector functions due to the presence of the Fc domain. Y. Liu teaches that constructs with specificity against CD3 and tumor-associated antigens have clear utility in the treatment of cancer. There would have been a reasonable expectation of success because the skilled artisan would have recognized that there are a finite number of ways in which the binding domains of the polypeptide chains within the scDb-Fc constructs may be arranged, and it was within the skill of one of ordinary skill in the art at the time of filing to try alternative configurations to optimize its functionality.
(2)
Claims 76, 78-79, and 86 are rejected under 35 U.S.C. 103 as being unpatentable over Alt (FEBS Letters (1999) 454: 90-94; supra) in view of Y. Liu (WO 2021/035096 A1; supra) as applied to claims 76-78, 84-85, and 87 above, and further in view of Bianchi (WO 2022/190016 A1; earliest priority date: March 9, 2021; cited in IDS), Inamura (Oncotarget (2017) 8(17): 28725-28735), Salgia (Seminars in Oncology (2009) 36(2, Suppl. 1): S52-S58), and C. Liu (Journal of Translational Medicine (2019) 17: Article 344).
The teachings of Alt with respect to scDb-Fcs are recited above.
However, Alt does not expressly teach a tetraspecific scDb-Fc construct that comprises an antigen-binding domain specific for each of CD3, CD28, c-Met, and TROP2, nor does Alt teach a kit comprising such a protein.
The teachings of Y. Liu are recited in the 35 U.S.C. § 103 rejection above.
Bianchi discloses recombinant multispecific T-cell engager proteins with specificity for different targets and use thereof in treating cancer (e.g., Abstract; page 1). In embodiments of the invention, Bianchi teaches a recombinant protein (e.g., an antibody) in which the first binding agent is specific for CD3 and the second, third, and fourth binding agents bind to distinct tumor-associated antigens (e.g., claims 3-4 and 11-15), relevant to claims 78-79. Relevant to claim 86, Bianchi further provides kits comprising a recombinant protein of the invention1 (e.g., pages 87-88).
Inamura teaches that TROP2 (TACSTD2) is highly expressed in many cancers and is a promising target for lung cancer (e.g., Abstract; Introduction). Inamura observed that high TROP2 expression is observed in 64% of adenocarcinomas, 75% of squamous cell carcinomas, and 18% of high-grade neuroendocrine tumors (HGNETs) via immunohistochemistry (e.g., Results, page 28726; Table 1). Inamura teaches that HGNETs includes SCLC and large cell neuroendocrine carcinoma (LCNEC), the latter of which is a biologically heterogeneous group containing SCLC-phenotype/NSCLC-phenotype cancers (e.g., Discussion, pages 28730-28731). Inamura reports that higher TROP2 expression was associated with higher patient mortality in HGNETs (e.g., Discussion, page 28730).
Salgia teaches that overexpression of c-Met (HGFR) is also observed in many cancers, including non-small cell lung cancer (NSCLC) and certain cells of SCLC (e.g., Abstract; Introduction).
C. Liu evaluated the prognostic value of peripheral CD8+CD28+ T cells in advanced NSCLC (e.g., Abstract). C. Liu teaches that activation of T cells via CD28 exerts immune responses against tumors, but that CD28 expression in CD8+ T cells may be downregulated in cancer patients due to chronic stimulation from tumor antigens (e.g., Introduction). C. Liu reports that increased levels of CD8+CD28+ T cells predicted better overall survival (OS) and progression-free survival (PFS) (e.g., Abstract; Results).
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the tetravalent scDb-Fc construct illustrated by Alt, arranged in a VL-VL-VH-VH configuration as suggested by Y. Liu, such that the construct is tetraspecific for each of CD3, CD28, TROP2, and c-Met based on the further teachings of Bianchi, Inamura, Salgia, and C. Liu. The skilled artisan would have been motivated to do so because such a construct would have clear utility in treating a cancer (e.g., lung cancer) in which aberrant expression of TROP2, c-Met, and CD28 is observed. In the present case, a construct that co-targets CD3, CD28, TROP2, and c-Met would have utility in directing activated CD3+/CD28+ T cells to TROP2+/c-MET+ tumor cells and facilitating T cell-mediated cytotoxicity against the tumor cells. There would have been a reasonable expectation of success because Inamura, Salgia, and C. Liu provide that TROP2, c-Met, and CD28 are each implicated in at least lung cancer, and Bianchi provides a proof-of-concept for developing multispecific T-cell engagers that bind to CD3 and three distinct tumor-associated antigens.
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.
(1)
Claims 76-78, 82, and 84-87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 128-150 of co-pending Application No. 17/936,041 (reference application) over Y. Liu (WO 2021/035096 A1; supra), Bianchi (WO 2022/190016 A1; supra), Inamura (Oncotarget (2017) 8(17): 28725-28735; supra), Salgia (Seminars in Oncology (2009) 36(2, Suppl. 1): S52-S58; supra), and C. Liu (Journal of Translational Medicine (2019) 17: Article 344; supra).
Relevant to claims 76-77, co-pending claims 128 and 130 recite an antigen-binding polypeptide comprising a first polypeptide and a second polypeptide, wherein the first polypeptide has a structure represented by “VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc” and the second polypeptide has a structure represented by “VL3-L5-VL4-L6-VH4-L7-VH3-L8-Fc”, wherein VL1-VL4 are immunoglobulin light chain variable regions and VH1-VH4 are immunoglobulin heavy chain variable regions, L1-L8 are amino acid linkers, and Fc comprises an immunoglobulin CH2, CH3, (optionally) an immunoglobulin hinge. Co-pending claim 133 recites that each of the variable domains bind to different antigens. Relevant to claim 82, co-pending claim 134 recites that the linkers L1-L8 each comprise “any one of SEQ ID NOs:1-19 and 681-688”, wherein SEQ ID NO: 1 shares 100% sequence identity with instant SEQ ID NO: 1, SEQ ID NO: 6 shares 100% sequence identity with instant SEQ ID NO: 7, and SEQ ID NO: 12 shares 100% sequence identity with instant SEQ ID NO: 14.
Co-pending claims 140-142 recite an antibody or antigen-binding fragment thereof comprising the antigen-binding polypeptide complex of co-pending claim 128, relevant to claim 84. Co-pending claim 147 recites a pharmaceutical composition comprising said antigen-binding polypeptide complex, pertinent to claim 85. Co-pending claim 149 recites a method of treating a cancer that comprises administering said complex, pertinent to claim 87.
The co-pending reference application does not expressly claim that the first through third variable domains of the antigen-binding polypeptide complex each bind to a tumor-associated antigen, specifically TROP2, c-Met, and CD28, and that the fourth variable domain binds to CD3. However, these deficiencies are remedied by Y. Liu, Bianchi, Inamura, Salgia, and C. Liu as taught in the 35 U.S.C. § 103 rejections above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the antigen-binding polypeptide of the co-pending reference application such that the antigen-binding domains specifically bind to CD3, CD28, TROP2, and c-Met. The skilled artisan would have been motivated to do so because Y. Liu teaches that scDb constructs having a similar structure and specificity against CD3 and one or more tumor-associated antigens, have clear utility in the treatment of cancer. There would have been a reasonable expectation of success because TROP2, c-Met, and CD28 are all commonly implicated in at least one cancer (lung cancer) as provided by Inamura, Salgia, and C. Liu, and because Bianchi provides a proof-of-concept for the generation of a tetraspecific T-cell engager proteins.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 80-81 and 83 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
1 Regarding the “instructions for use” recited in the instant claim, nonfunctional printed matter does not distinguish a claimed product from an otherwise identical prior art product. See MPEP § 2112.01 (III). Furthermore, “instructions for use” are included in kits, and one of ordinary skill in the art would at once envisage that instructions are needed, so one would be motivated to include such “instructions” to ease the use of the composition
Prosecution Insights