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 .
Claim Status
Claims 12-15, 17-20, 22-24, 26-28, 31-47 and 52-61 were canceled.
Claims 1-11, 16, 21, 25, 29-30, and 48-51 are pending and under consideration.
Specification
The disclosure is objected to because they depict nucleic acid and/or amino acid sequences (G4S)n, (SG4)n, and G4(SG4)n, which is not identified by sequence identification numbers in [00314] and [00316] at page 53. Applicant must provide appropriate amendments to the specification inserting the required sequence identifiers.
Appropriate action correcting this deficiency is required. If any sequences are not in the current sequence listing, Applicant must submit paper and computer-readable copies of a substitute sequence listing, together with an amendment directing its entry into the specification and a statement that the content of both copies are the same and, where applicable, include no new matter.
Sequences appearing in the specification and/or drawings must be identified by a sequence identifier in accordance with 37 C.F.R. 1.821(d); sequence identifiers for sequences appearing in the drawings may appear in the drawings or in the brief description of the drawings.
Appropriate correction is required.
Claim Objections
Claims 48 and 50 are objected to because of the following informalities: conjunction “and” is needed before the last member of Markush group because proper Markush group requires the format of “selected from the group consisting of A, B, C and D”. See MPEP 2173.05(h) for proper Markush group format. Appropriate correction is required.
Claim 51 is objected to because of the following informalities: “FGF” is repeated in line 3. Appropriate correction is required.
Claim 51 is objected to because of the following informalities: “and THBS” in line 5 should read “THBS”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11, 16, 21, 25, 29-30, and 48-51 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 1 recites “the first antigen is targeted to antigens associated with tumorigenesis”. It is unclear (i) if Applicant intends to recite that the first antigen binds to antigens associated with tumorigenesis; or (ii) if Applicant intends to recite that the first antigen is antigen associated with tumorigenesis. In case of (i), what does Applicant mean by antigen binding to antigen?
Claim 1 recites “tumorigenesis or progression”. It is unclear what Applicant intends to recite by “progression” because claim 1 does not recite any modifying phrase following “progression”. Does Applicant intend to mean “progression of tumor formation” by “progression”? Or does Applicant intend to mean metastasis by “progression”?
Claim 2 recites “the antigen targeting the tumorigenesis or progression”. There is insufficient antecedent basis for this limitation in the claim. While claim 1 recites “antigens associated with tumorigenesis or progression”, claim 1 does not recite “an antigen targeting the tumorigenesis or progression”. If Applicant intends to recite about the first antigen, it is suggested that Applicant amend wherein-clause of claim 2 to “wherein the first antigen is a tumor-associated antigen (TAA) and/or a tumor-specific antigen (TSA)”. Hereinafter, claim 2 will be interpreted as if claim 2 recites that the first antigen is a tumor-associated antigen (TAA) and/or a tumor-specific antigen (TSA).
Claims 4 and 49-50 recite “the second antigen”. There is insufficient antecedent basis for this limitation in the claim. Claim 49-50 depend from claim 5 which in turn depends from claim 3 and claim 1 directly and indirectly. However, none of claims 1, 3, and 5 recites “a second antigen”.
Claim 4 recites “the second antigen-binding protein” in line 2-3. There is insufficient antecedent basis for this limitation in the claim. While claim 1 recites “a second antigen-binding portion”, claim 1 does not recite “a second antigen-binding protein”.
Claim 30 recites “between any one of”. One of ordinary skill in the art would be able to understand the exact location of the third antigen-binding portion when it is recited between A and B. Because claim 30 recites “between any one of”, the location of the third antigen-binding portion is not clear.
Claim 48 recites “CD20 (MS4A1)”, “BIRC5 (survivin)”, “PSMA (FOLH1)”, “ferritin (SF)” and “squamous cell antigen (SCC)” which are exemplary claim languages and it is unclear the content in parenthesis is limiting or merely exemplary. Parenthesis in claims is permitted only for definition of the term.
Dependent claims are also rejected because they depend from claim 1 and do not cure the deficiency.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-11, 16, 21, 25, 29-30, and 48-51 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a “written description” rejection.
“[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). See also MPEP 2163.04.
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. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[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) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the 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 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 antibodies, 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, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Additionally, “An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.” Amgen Inc v. Sanofi 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). “Further, the “newly characterized antigen” test flouts basic legal principles of the written description requirement. Section 112 requires a “written description of the invention.” But this test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law's other requirements are met, one obtains a patent.” Ariad, 598 F.3d at 1345.” Amgen at 1362.
Claim Analysis
Instant claims are drawn to a multispecific antigen-binding protein, comprising: (a) a first antigen-binding portion that specifically recognizes the first antigen, wherein the first antigen is specifically targeted to antigens associated with tumorigenesis or progression; (b) a second antigen-binding portion, wherein the second antigen-binding portion is an innate immune cell agonist; and (c) a third antigen-binding portion that specifically recognizes the third antigen, wherein the third antigen regulates tumor microenvironment by regulating normal and abnormal angiogenesis; wherein the positions of the second antigen-binding portion and the third antigen-binding portion are interchangeable.
Instant specification disclosed a multispecific antigen-binding protein comprising (a) a first antigen-binding portion binding to claudin 18.2; (b) a second antigen-binding portion binding to NKp30; and (c) a third antigen-binding portion binding to VEGF (Example 1, page 97). The third antigen-binding portion targets VEGF in the form of VEGF receptor or scFv. Therefore, instant specification disclosed two species multispecific antigen-binding proteins: one with VEGF receptor (named as CNVR-A to CNVR-F) and the other with VEGF scFv (named CNV-A to CNV-F).
In contrast, instant claims encompass multispecific protein comprising (a) a first antigen-binding portion binding to any tumor-associated antigen; (b) a second antigen-binding portion binding to any receptor on immune cell; and (c) a third antigen-binding portion binding to any antigen wherein the antigen regulates tumor microenvironment. Claims 48-51 recite specific antigen for one of the three antigens, but do not define the other two. Furthermore, claim 48 recites 140 TAAs. Only a single species multispecific protein binding to claudin18.2 cannot be considered as a representative number of species falling within the scope of genus encompassing multispecific proteins binding to 140 different TAA antigens. Likewise, claim 49 recites 10 different second antigens and claim 51 recites 50 different third antigens. Therefore, instant claims 48-51 encompasses at least 140x10x50 = 70,000 different species multispecific proteins binding to 70,000 different antigens. Only a single species binding to claudin18.2, NKP30, and VEGF disclosed by instant specification cannot be considered as a representative number of species falling within the scope of genus encompassing 70,000 different species binding to 70,000 different antigens. While instant specification shows that Applicant is in possession of a single species multispecific protein binding to claudin18.2, NKP30, and VEGF, instant specification does not provide adequate written description for multispecific proteins binding to any possible first, second and third antigens as recited by instant claim 1.
Claims 7 and 8 recite conjunction “or” between VH and VL. Although single domain antibody VHH is known in the art, functional antibody comprising only VH or VL is not known in the art. A skilled artisan in the art would recognize that antibodies require all six CDRs to specifically bind to its antigen except well-known single domain antibody VHH. Therefore, instant specification and prior art do not provide adequate written description for instant claims 7-8 reciting antibody fragment comprising only VH or VL domain.
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-9, 48-49 and 51 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Loew et al (US2017/0368169; 1/30/2024 IDS).
Regarding claim 1 and 51, Loew teaches “Multispecific molecules that include i) a tumor-targeting moiety (corresponds to first antigen-binding portion of instant claim 1); and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager) (corresponds to second antigen-binding portion of instant claim 1); (iii) a cytokine molecule (corresponds to third antigen-binding portion of instant claim 1); and/or (iv) a stromal modifying moiety are disclosed.” (abstract). Loew teaches “Examples of useful cytokines include, but are not limited to, GM-CSF, IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-21, IFN-α, IFN-β, IFN-γ, MIP-1α, MIP-1β, TGF-β, TNF-α, and TNFβ.” [0649]. It is well known in the art that IL-6 binds to IL-6 receptor to regulate tumor microenvironment. Therefore, cytokine IL-6 of Loew corresponds to “third antigen-binding portion” of instant claim 1.
Regarding claim 2, claim 1 of Loew teaches that a first tumor-targeting moiety binds to a cancer antigen.
Regarding claim 3-4, Loew teaches “In other embodiments, the immune cell engager binds to and activates an immune cell, e.g., an effector cell.” [0090]. Loew teaches “In some embodiments, the immune cell engager antibody molecule binds to the NK cell antigen, the B cell antigen, the dendritic cell antigen, and/or the macrophage cell antigen” [0136]. Therefore, NK cell antigen of Loew is NK cell agonist.
Regarding claim 5, it is well known in the art that IL-6 binds to IL-6 receptor and activates downstream pathways which stimulates new blood vessel formation (angiogenesis). Therefore, IL-6 receptor taught by Loew corresponds to third antigen and pro-angiogenic factor recited by instant claim 5.
Regarding claim 6-9, Loew teaches “immune cell engagers include an antibody molecule” [0026]. Loew teaches “an antibody molecule encompasses full-length antibody and antibody fragments” [0403]. Loew teaches “the tumor targeting antibody molecule and/or immune cell engager antibody molecule is a full antibody (e.g., an antibody that includes at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains), or an antigen-binding fragment (e.g., a Fab, F(ab′)2, Fv, a single chain Fv, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody).” [0143]. Loew teaches “variable domain derived from a heavy chain antibody naturally devoid of light chain is known herein as a VHH or nanobody to distinguish it from the conventional VH of four chain immunoglobulins. Such a VHH molecule can be derived from antibodies raised in Camelidae species, for example in camel, llama, dromedary, alpaca and guanaco” [0434].
Regarding claim 48, claim 38 of Loew teaches that the cancer antigen is a hematological antigen chosen from CD19, CD33, CD47, CD123, CD20, CD99, CD30, BCMA, CD38, CD22, SLAMF7, or NY-ESO1.
Regarding claim 49, claim 29 of Loew teaches “the NK cell engager is chosen from an antibody molecule or ligand that binds to: NKp30, NKp40, NKp44, NKp46, NKG2D, DNAM1, DAP10, CD16a, CD16b, CRTAM, CD27, PSGL1, CD96, CD100, NKp80, CD244, SLAMF6, SLAMF7, KIR2DS2, KIR2DS4, KIR3DS1, KIR2DS3, KIR2DS5, KIR2DS1, CD94, NKG2C, NKG2E, or CD160”.
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.
NSDP1
Claims 1-11, 16, 21, 25, 29-30, 48-49 and 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-10, 15, 20, 24, 28-29, and 47-49 of copending Application No. 18/293500 (hereinafter application’500; US2024/0336682; PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 1-2, claim 1 of application’500 claims “A multispecific antigen-binding protein, comprising: (a) a first antigen-binding portion that specifically recognizes the first antigen, wherein the first antigen is a tumor-associated antigen (TAA); (b) a second antigen-binding portion, wherein the second antigen-binding portion is an innate immune cell agonist; and (c) a third antigen-binding portion that specifically recognizes the third antigen, wherein the third antigen regulates the tumor microenvironment; wherein the positions of the second antigen-binding portion and the third antigen-binding portion are interchangeable.”
Regarding claim 3, claim 2 of application’500 claims that the innate immune cell agonist is an NK cell agonist.
Regarding claim 4, claim 3 of application’500 claims that the second antigen-binding protein specifically recognizes the second antigen expressed on the innate immune cells, and the second antigen-binding protein activates the innate immune cells after binding to the second antigen.
Regarding claim 5 and 51, claim 49 of application’500 claims that the third antigen is TGF-β, IL-6 or VEGF. VEGF is a pro-angiogenic factor.
Regarding claim 6, claim 5 of application’500 claims that the first antigen-binding portion and/or the second antigen-binding portion and/or the third antigen-binding portion is a full-length antibody comprising two heavy chains and two light chains.
Regarding claim 7, claim 6 of application’500 claims that the first antigen-binding portion and/or the second antigen- binding portion and/or the third antigen-binding portion is an antibody fragment comprising a heavy chain variable domain (VH) and/or a light chain variable domain (VL).
Regarding claim 8, claim 7 of application’500 claims that the first antigen-binding portion and/or the second antigen-binding portion and/or the third antigen-binding portion is one of Fab, scFab, F(ab')2, Fv, dsFv, scFv, VH or VL structural domain.
Regarding claim 9, claim 8 of application’500 claims that the first antigen-binding portion and/or the second antigen- binding portion and/or the third antigen-binding portion is a single-domain antibody (VHH).
Regarding claim 10, claim 9 of application’500 claims that the first antigen-binding portion and/or the second antigen- binding portion and/or the third antigen-binding portion is a receptor for an antigen.
Regarding claim 11, claim 10 of application’500 claims that the second antigen-binding portion is fused to the N-terminus and/or C-terminus of one of the heavy chains of the first antigen-binding portion.
Regarding claim 16, claim 15 of application’500 claims that the second antigen-binding portion is fused to the N- terminus and/or C-terminus of one of the light chains of the first antigen-binding portion.
Regarding claim 21, claim 20 of application’500 claims that the second antigen-binding portion is fused to the N- terminus and/or C-terminus of both heavy chains of the first antigen-binding portion.
Regarding claim 25, claim 24 of application’500 claims that the second antigen-binding portion is fused to the N- terminus and/or C-terminus of both light chains of the first antigen-binding portion.
Regarding claim 29, claim 28 of application’500 claims that the third antigen-binding portion replaces one or more binding units of: Fab region or Fv region or VH, CH1 domain, CH2 domain, or CH3 domain of the first antigen-binding portion, and/or the second antigen-binding portion.
Regarding claim 30, claim 29 of application’500 claims that the third antigen-binding portion is located between any one of: VH, CH1 domain, CH2 domain, and CH3 domain of the first antigen-binding portion and/or the second antigen-binding portion.
Regarding claim 48, claim 47 of application’500 claims same set of TAA as instant claim 48.
Regarding claim 49, claim 48 of application’500 claims that the second antigen is selected from the group consisting of: NKP30, NKP46, CD16, NKP44, CD244, CD226, NKG2E, NKG2D, NKG2C, and KIR.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
NSDP2
Claims 1-11, 16, 21, 25, 29-30, 48-49 and 51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 46-48 of copending Application No. 18/569320 (hereinafter application’320; US2024/0218065; PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 1-3, 5, 10 and 51, claim 1 of application’320 claims “A multispecific antigen-binding protein, comprising: (a) a first antigen-binding portion that specifically recognizes the first antigen, wherein the first antigen is a tumor associated antigen (TAA); (b) a second antigen-binding portion, wherein the second antigen-binding portion is an NK cell activator; and (c) a third functional portion, wherein the third functional portion comprises a cytokine and/or a cytokine receptor.” Claim 48 of application’320 claims same cytokine IL-6 and IL-8 as instant claim 51. Therefore, Cytokine receptor of application’320 bind to same cytokine IL-6 and IL-8 as recited by instant claim 51 and corresponds to “third antigen-binding portion” of instant claim 1. It is well known in the art that IL-6 and IL-8 are pro-angiogenic factors as recited by instant claim 5.
Regarding claim 4, claim 2 of application’320 claims that the second antigen-binding portion specifically recognizes a second antigen expressed on NK cells, and the second antigen-binding portion activates the NK cells upon binding to the second antigen.
Regarding claim 6, claim 3 of application’320 claims that the first antigen-binding portion and/or the second antigen-binding portion is a full-length antibody comprising two heavy chains and two light chains.
Regarding claim 7, claim 4 of application’320 claims that the first antigen-binding portion and/or the second antigen-binding portion is an antibody fragment comprising a heavy chain variable domain (VH) and/or a light chain variable domain (VL).
Regarding claim 8, claim 5 of application’320 claims that the first antigen-binding portion and/or the second antigen-binding portion is one of Fab, scFab, F(ab')2, Fv, dsFv, scFv, VH or VL structural domain.
Regarding claim 9, claim 6 of application’320 claims that the first antigen-binding portion and/or the second antigen-binding portion is a single-domain antibody (VHH).
Regarding claims 11, 16, 21, and 25, these different orientation of components of the fusion protein are obvious to one of ordinary skill in the art. Making protein construct in the different orientation of components was routine experimentation to one of ordinary skill in the art at the time the claimed invention was filed.
Regarding claim 29, claim 8 of application’320 claims that the third functional portion replaces one or more of: the CH1 structural domains, the CH2 structural domains, the CH3 structural domains of the heavy chain of the first antigen-binding portion, and/or the second antigen-binding portion.
Regarding claim 30, claim 7 of application’320 claims that the third functional portion is located between the CH1 structural domain and the CH2 structural domain, or the third functional portion is located between the CH2 structural domain and the CH3 structural domain, or the third functional portion is located between the VH structural domain and the CH1 structural domain, of the first antigen-binding portion and/or the second antigen-binding portion.
Regarding claim 48, claim 46 of application’320 claims same TAA as recited by instant claim 48.
Regarding claim 49, claim 47 of application’320 claims that the second antigen is selected from the group consisting of: NKP30, NKP46, CD16, NKP44, CD244, CD226, NKG2E, NKG2D, NKG2C, KIR.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHEOM-GIL CHEONG whose telephone number is (571)272-6251. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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