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 .
1. Claims 1-10, 16, 17, 23, 24,38, 42, 54, 67, 73, 84, 95, 106, 113, 122, 129, 138, and 140 are pending and being examined.
It is noted that the terms CD137 and 4-1BB refer to the same protein.
Claim Objections
2. Claim 6 is objected to for minor informalities. Claim 6 contains an apostrophe after the sequence “ARTERIALS”. The apostrophe should be deleted. 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.
3. Claims 2, 4, 10, 24, 38, 42, and 73 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 2 is directed to a multispecific antigen-binding protein product, however, the claim recites an active method step of “optionally wherein pure agonist activity is determined by an NF-κB pathway activation assay in the absence of a cross-linking agent.” The optional limitation renders the claimed scope of the invention unclear as to whether a product or a method is being claimed.
Regarding claims 4, 10, and 24, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by “such as” and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd.App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
In the present instance, claim 4 recites the broad recitation of ISV specifically binding to 4-1BB and interacting with CRD2 and/or CRD3 domain of 4-1BB, and the claim also recites “preferably the at least one ISV specifically binding to 4-1BB interacts with the CRD2 and CRD3 domains of 4-1BB”, which is the narrower statement of the range/limitation.
In the present instance, claim 10 recites the broad recitation of the at least one ISV specifically binding to 4-1BB comprises or consists of SEQ ID NO:2 or 3, and the claim also recites “preferably wherein the at least one ISV specifically binding to 4-1BB comprises or consists of an amino acid sequence of SEQ ID NO:3”, which is the narrower statement of the range/limitation.
In the present instance, claim 24 recites the broad recitation of a) a first polypeptide comprising i.-iv. features in any order, and the claim also recites “preferably from N-terminus to C-terminus” arrangement of i.-iv. features, which is the narrower statement of the range/limitation.
Additionally, claim 24 recites the broad recitation of ii. a second ISV specifically binding to 4-1BB that encompasses second ISV identical to first ISV, and the claim also recites “preferably wherein the second ISV is different from the first ISV” which is the narrower statement of the range/limitation.
Claim 38 recites the Fab fragment binding to PD-1 comprises “a light chain variable region with SEQ ID NO:7 and a heavy chain variable region with SEQ ID NO:8.” It is unclear how SEQ ID NO:7 and 8 are associated “with” the light chain variable region and heavy chain variable region comprised by the Fab fragment. The metes and bounds of the claimed fab fragment cannot be determined. Examiner suggests amending claim 38 to recite “comprises the light chain variable region SEQ ID NO:7 and the heavy chain variable region SEQ ID NO:8”.
Claim 42 depends from claim 1 and recites a conditionally-active multispecific antigen-binding protein comprising: “(ii) at least one masking moiety reducing or inhibiting the binding of the multispecific antigen-binding protein to at least one of its target antigens.” There is insufficient antecedent basis for this limitation in the claim because claim 1 does not recite target antigens.
Claim 73 depends from claim 67 and recites a conditionally-active single variable domain (ISV) comprising: “(ii) at least one masking moiety reducing or inhibiting the binding of ISV to its target antigen.” There is insufficient antecedent basis for this limitation in the claim because claim 67 does not recite a target antigen.
Claim Interpretation
4. Claim 9 recites the ISV comprises or consists of: (i) an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 3, 58, 59, 60, and 61. This claim limitation is reasonably and broadly interpreted to encompass any amino acid sequences as few as two consecution amino acids long (“an amino acid sequence”) found in (“selected from”) any of SEQ ID NOs:2, 3, 58, 59, 60, and 61. Claim 9 part (i) is not limited to the amino acid sequence selected from the group consisting of SEQ ID NOs:2, 3, 58, 59, 60, and 61.
Claim 10 recites the ISV comprises or consists of “an amino acid sequence of SEQ ID NO:2 or 3” and “an amino acid sequence of SEQ ID NO:3”. This claim limitation is reasonably and broadly interpreted to encompass any amino acid sequence as few as two consecution amino acids long (“an amino acid sequence”) found in (“of”) SEQ ID NO:2 or 3. Claim 10 is not limited to the amino acid sequence of SEQ ID NO:2 or 3.
Claim 67 recites the ISV comprises or consists of: “(i) an amino acid sequence selected from the group consisting of SEQ ID NOs:1 and 4”. This claim limitation is reasonably and broadly interpreted to encompass any amino acid sequences as few as two consecution amino acids long (“an amino acid sequence”) found in (“selected from”) any of SEQ ID NOs:1 and 4.
Claim 106 recites an antibody comprising: “(i) three light chain CDR sequences found in SEQ ID NO:7 or 5, and (ii) three heavy chain CDR sequences found in SEQ ID NO:8 or 6.” This claim limitation reasonably broadly encompasses any sequence fragments as few as two consecutive amino acids long found in SEQ ID NOs:5-8.
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.
5. Claims 1-10, 16, 17, 23, 24,38, 42, 54, 67, 73, 84, 95, 106, 113, 122, 129, 138, and 140 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.
The are drawn to an immunoglobulin single variable domain (ISV) or multispecific antigen-binding protein comprising an ISV, wherein the ISV functions to:
specifically bind to 4-1BB;
have pure agonist activity;
compete with 4-1BBL for 4-1BB binding;
interact with the cysteine-rich domain 2 (CRD2) and/or cysteine-rich domain 3 (CRD3) domain of 4-1BB; preferably the at least one ISV specifically binding to 4-1BB interacts with the CRD2 and CRD3 domains of 4-1BB; and
interact with one or several amino acid residues of 4-1BB selected from the group consisting of residues K69, G70, V71, F72, R73, F92, L95, S100, M101, C102, E103, Q104, K114, K115 and G116 of SEQ ID NO: 13.
Thus, the claims identify the ISV by function only, as listed above. No ISV structure is recited that is critical to performing the claimed functions.
Claims 6-8 recite a partial sequence structure of the ISV specifically binding to 4-1BB, defining one sequence of CDR1, CDR2, or CDR3, encompassing a vast genus of CDR variants having any alternative CDRs in addition to the single CDR defined, where at least two CDR sequences critical to the 4-1BB-binding function are unknown and undefined.
Claim 9 part (i) recites a partial sequence structure of the ISV specifically binding to 4-1BB, wherein the ISV (VHH) comprises or consists of “an amino acid sequence selected from” any of SEQ ID NOs: 2, 3, and 58-61, encompassing a vast genus of sequence variants sharing as small as two consecutive amino acids with SEQ ID NOs: 2, 3, and 58-61.
Claim 9 part (ii) recites a partial sequence structure of the ISV specifically binding to 4-1BB, wherein the ISV (VHH) can have up to 30% sequence discrepancy from SEQ ID NOs: 2, 3, and 58-61, encompassing a vast genus of sequence variants having any sequence mutations and variations within the CDR regions critical to the claimed 4-1BB-binding function.
Claim 67 recites an ISV specifically binding to 4-1BB and (ii) an amino acid sequence sharing at least 70% sequence identity over the non-CDR regions of SEQ ID NOs:1 or 4, which encompasses a vast genus of ISV having no required sequence identity to the CDRs of SEQ ID NOs:1 and 4 that are critical to performing the 4-1BB-binding function. The sequence of the CDRs in this genus that are critical to performing the 4-1BB-binding function are undefined and unknown.
Claim 95 is drawn to a conditionally-active ISV that functions to specifically bind to “a target antigen”. Claim 95 does not recite any recognizable structure of the ISV required to bind a target antigen.
Claim 106 recites an antibody comprising: “(i) three light chain CDR sequences found in SEQ ID NO:7 or 5, and (ii) three heavy chain CDR sequences found in SEQ ID NO:8 or 6.” This claim limitation reasonably encompasses any CDR sequence fragments as few as two consecutive amino acids long found in SEQ ID NOs:5-8. The specification only contemplates light chain variable region SEQ ID NOs:5 and 7, and heavy chain variable region SEQ ID NOs:6 and 8 functioning together as an antibody binding to PD-1. Claim 106 encompasses a vast genus of antibody sequence variants comprising as few as two consecutive amino acids from CDRs found SEQ ID NOs:5-8.
Thus, the claims identify the ISV or antibodies by function only, or by function and partial sequence structure.
With regard to immunoglobulin single variable domain (ISV), the instant specification discloses:
[0247] In contrast, immunoglobulin single variable domains are capable of specifically binding to an epitope of the antigen without pairing with an additional immunoglobulin variable domain. The binding site of an immunoglobulin single variable domain is formed by a single VH, a single VHH or single VL domain. Hence, the antigen binding site of an immunoglobulin single variable domain is formed by no more than three CDRs. As such, the single variable domain may be a light chain variable domain sequence (e.g., a VL-sequence) or a suitable fragment thereof, or a heavy chain variable domain sequence (e.g., a VH-sequence or VHH sequence) or a suitable fragment thereof, as long as it is capable of forming a single antigen-binding unit (i.e., a functional antigen-binding unit that essentially consists of the single variable domain, such that the single antigen-binding domain does not need to interact with another variable domain to form a functional antigen-binding unit).
[0248] An immunoglobulin single variable domain (ISV) can for example be a heavy chain ISV, such as a VH, VHH, including a camelized VH or humanized VHH. In one embodiment, it is a VHH, including a camelized VH or humanized VHH. Heavy chain ISVs can be derived from a conventional four-chain antibody or from a heavy chain antibody. For example, the immunoglobulin single variable domain may be a (single) domain antibody (or an amino acid sequence that is suitable for use as a single domain antibody), a “dAb” or dAb (or an amino acid sequence that is suitable for use as a dAb) or a Nanobody® ISV (as defined herein and including, but not limited to, a VHH); other single variable domains, or any suitable fragment of any one thereof. In particular, the immunoglobulin single variable domain may be a Nanobody® ISV (such as a VHH, including a humanized VHH or camelized VH) or a suitable fragment thereof.
Thus, “ISV” broadly encompasses antibodies comprising only the light chain variable domain (VL) three CDRs, or only the heavy chain variable domain (VH or VHH) three CDRs, or “any suitable fragment of any one thereof”.
The instant specification discloses the sequences of anti-4-1BB ISV (VHH) and identifies the three CDR sequences (CDRs1-3) of each ISV critical to the 4-1BB binding function:
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The specification discloses the sequences of two anti-PD-1 antibodies comprising light and heavy chain variable regions and identifies the six CDR sequences critical to the PD-1 binding function:
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Thus, the instant specification describes eight anti-4-1BB VHH (ISV) comprising three defined CDR1-3 sequences critical to the claimed 4-1BB-binding function. The instant specification describes two anti-PD-1 antibodies comprising 6 CDR sequence critical to PD-1-bidning function as contemplated. The specification fails to disclose the structural sequence required of any sequence variants of these VHH and antibodies that would function as claimed and contemplated.
To provide adequate written description and evidence of possession of the claimed ISV and antibody genus, the instant specification can structurally describe representative ISV and antibodies that function to bind 4-1BB or PD-1 and as claimed and contemplated, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
With regard to anti-41BB ISV, the only factor present in the claims is a recitation of the ISV function as listed above, or partial ISV sequence structure. With regard to PD-1 antibodies, the only factor present in the claims is a recitation of function or a partial sequence structure. Other than for the few species of anti-4-1BB ISV and anti-PD-1 antibodies disclosed, the instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus, because the instant specification fails to disclose a sufficiently representative number of exemplary ISV and antibody sequences that function as claimed and contemplated by the specification. A definition by function does not suffice to define the genus because it is only an indication of what the antibody and ISV do, rather than what they are. The specification fails to provide any structural features coupled to the claimed functional characteristics. Other than for the few species of anti-4-1BB ISV and anti-PD-1 antibodies disclosed, the instant specification fails to describe a representative number of antibody sequences for the vast genus of ISV and antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
The claims broadly encompass any anti-4-1BB ISV and sequence variants that functions as claimed and listed above. The claims broadly encompass any anti-PD-1 antibody and sequence variants. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the variable domains or CDRs that can be altered and still maintain 4-1BB or PD-1 binding function, and function as claimed and contemplated by the specification. The instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses only eight anti-4-1BB VHH (ISV) comprising three defined CDR sequences critical to the 4-1BB- binding function and functions claimed, and discloses only two anti-PD-1 antibodies comprising six defined CDRs critical to PD-1 binding contemplated and claimed. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of ISV and antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of the few exemplary ISV and antibody sequences to the structure of any and all anti-4-1BB ISV and anti-PD-1 antibodies, as broadly claimed and required to practice the claimed invention. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for ISV or antibodies that bind 4-1BB or PD-1 and function as claimed, 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 agents or antibodies yet to be discovered that may function as claimed. The 4-1BB and PD-1 antigens provide no information about the structure of an ISV or antibody that binds to them.
Given the lack of representative examples to support the full scope of the claimed ISV and antibodies, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs that provide the claimed and contemplated functions, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of ISV and antibodies that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: With regard to ISV and ISV binding 4-1BB, amend the claims to recite and require, at minimum, the three CDR1-3 sequences critical to the 4-1BB binding and claimed functions. With regard to the anti-PD-1 antibodies, amend the claims to recite and require, at minimum, the six CDR sequences from the heavy and light chain variable domains.
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.
6. Claim 54 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhai et al (Journal of Immunother. Cancer, 2021; 9:e002131).
Zhai teaches and successfully exemplifies producing a single domain VHH agonist antibody against 4-1BB (Methods; Discussion).
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.
7. Claim(s) 1-3, 9, 10, 16, 17, 23, 42, 54, 67, 73, 84, 95, 113, 122, 129-140 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/149282 Luo et al, published August 2019; in view of Zhai et al (Journal of Immunother. Cancer, 2021; 9:e002131).
Luo teaches and successfully demonstrates making “activatable” (conditionally active) anti-CD137 (4-1BB) antibodies, wherein the antibodies are linked to a masking moiety (MM) that inhibits binding to CD137 until the MM is cleaved in the tumor microenvironment, and wherein the MM is attached to the antibody heavy chain variable region (Figure 2; [12], [15]; section III; [105]; [161]; [164]; [166]; [187]; [203-209]; claims 44, 59);
wherein the antibodies are agonists (activate NF-κB pathway and induce T-cell proliferation), and compete for binding to CD137 with CD137L ([209]; [215]);
wherein the antibodies encompass multispecific or bispecific antibodies ([66]; [233]);
wherein the antibodies are a dAb (domain antibody) which can consist of the VH domain or VL domain, or are NANOBODIES® (VHH), and wherein the antibody can comprise a Fab fragment ([71]; [122]; [161-164]; [218]; [220-221]; [224]; [233]; claims 31, 59)
Luo teaches production of domain antibodies and NANOBODIES® are well known in the art ([233]).
In Example 5, Luo teaches the VH sequence of the anti-CD137 antibody is SEQ ID NO:49 which comprises “an amino acid selected from SEQ ID NO:2”, “comprises an amino acid sequence of” instant SEQ ID NO:2, and comprises “an amino acid sequence selected from” SEQ ID NO:1 (see sequence alignments below demonstrating overlapping shared sequences as relevant to instant claims 9, 10, and 67).
Luo teaches polynucleotides encoding the antibodies ([6-7]; [11]; [24]; section III; [122-123]; [161]; [173]; claims 30, 33), vectors comprising the nucleic acids ([13]; [24]; section III; [123-126]; [173]; claims 34, 35); host cell comprising the polynucleotide ([13]; [24]; [125-133]; [173-179]; claims 36, 37, 61, 62); and methods of making the antibodies by expressing the polynucleotide encoding the antibodies in a cell ([13]; [24]; [123-133]; [173-179]; [233]; claims 38-40).
Luo teaches methods of treating cancer a subject comprising administering a pharmaceutical composition comprising the CD137 activatable antibody ([25]; [213]; section VIII; [240-244]; claims 94-97).
Luo teaches pharmaceutical composition comprising a pharmaceutically acceptable carrier and the CD137 antibodies, or masked (activatable) CD137 antibodies ([234]).
Luo suggests combining anti-cancer therapies with the activatable CD137 antibody for the treatment of cancer including anti-PD-L1 antibody ([25]; [246]; [248]; claim 97); and suggests making activatable anti-PD-L1 antibodies ([105]; [161]).
Luo teaches and suggests making and using single domain anti-CD137 (4-1BB) antibodies and multispecific antibodies for their masked (activatable) antibody, but does not exemplify making a single domain (VHH) CD137 antibody or multispecific antibody comprising the CD137 single domain and another single domain binding to an antigen expressed on T cells or tumor cells.
Zhai teaches and successfully exemplifies producing single-domain VHH agonist antibodies against 4-1BB as well as 4-1BB x PD-L1 bispecific VHH antibodies comprising a single-domain VHH agonist antibody against 4-1BB and a VHH against PD-L1, wherein PD-L1 is a tumor-associated antigen and T cell antigen (Figure 4; p. 7). Zhai demonstrates successfully treating cancer in subjects by administering the bispecific antibody, wherein treatment with the bispecific antibody was superior to that of administering a combination of separate 4-1BB and PD-L1 antibodies (p. 8; Figure 6).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to make and use a single domain VHH 4-1BB antibody and that is multispecific for the masked antibody of Luo. One would have been motivated to, and have a reasonable expectation of success to because: (1) Luo suggests making and using single domain and multispecific 4-1BB antibodies in their activatable antibody construction and for the purpose of treating cancer, Luo suggests attaching the masking moiety to a VH domain, and Luo teaches the construction of single VH domain antibodies is well known in the art; (2) Luo suggests combining anti-PD-L1 antibody therapy with their 4-1BB antibody for the treatment of cancer; (3) Zhai exemplifies successful production of a single domain 4-1BB antibody and 4-1BB x PD-L1 bispecific antibody comprising the single domain 4-1BB antibody; and (4) Zhai demonstrates that cancer treatment was superior for the 4-1BB x PD-L1 bispecific antibody comprising the single domain 4-1BB antibody as compared administering a combination of separate 4-1BB and PD-L1 single domain antibodies.
Instant SEQ ID NO:2 aligned with Luo anti-CD137 VH SEQ ID NO:49:
Qy= instant SEQ ID NO:2
Db = Luo SEQ ID NO:49
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Instant SEQ ID NO:1 aligned with Luo anti-CD137 VH SEQ ID NO:49:
Qy= instant SEQ ID NO:1
Db = Luo SEQ ID NO:49
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8. Claim(s) 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/149282 Luo et al, published August 2019; and Zhai et al (Journal of Immunother. Cancer, 2021; 9:e002131); as applied to claims 1-3, 9, 10, 16, 17, 23, 42, 54, 67, 73, 84, 95, 113, 122, 129-140 above, and further in view of WO 2021/262869, Luo et al (“Luo 2”), filed June 23, 2021, claiming priority to June 23, 2020.
The applied reference WO 2021/262869, Luo 2, has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Luo and Zhai (the combined references) teach a multispecific antibody comprising an agonistic anti-4-1BB VHH domain, as set forth above.
The combined references do not teach the anti-4-1BB antibody binds to 4-1BB at one or several amino acid residues of 4-1BB selected from the group consisting of K69, G70, V71, F72, R73, F92, L95, S100, C102, E103, Q014, K114, K115, and G116 of instant SEQ ID NO:13 which encompasses cysteine-rich domain 3 (CRD3) at amino acids 87-118.
Luo 2 teaches an anti-4-1BB antibody having agonist activity for the treatment of cancer, wherein the antibody binds to one or more amino acid residues selected from the group consisting of amino acid residues 51, 53, 62-73, 83, 89, 92, 95-104 and 112-116 of SEQ ID NO: 1, wherein SEQ ID NO:1 of Luo is 100% identical to instant SEQ ID NO:13 ([8-11]; [20]; [89-90]; [178-182]). Luo teaches the anti-4-1BB antibody includes multispecific antibodies and VH domain antibodies (dAbs) ([45]; [201-202]). Luo teaches their anti-CD137 antibody blocks CD137L from binding CD137 ([190]). Luo also suggests combining their anti-CD137 antibody with anti-PD-L1 antibody therapy for cancer treatment ([122-125]).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to make an anti-4-1BB VHH that binds to one or more amino acid residues selected from the group consisting of amino acid residues K69, G70, V71, F72, R73, F92, L95, S100, C102, E103, Q014, K114, K115, and G116 of instant SEQ ID NO: 13 in the activatable multispecific antibody of the combined references. One would have been motivated to, and have a reasonable expectation of success to because: (1) all of the combined references and Luo 2 teach making and using anti-4-1BB agonist antibody for the same purpose of treating cancer; and (2) Luo 2 teaches an antibody having this function should bind to one or more amino acid residues selected from the group consisting of amino acid residues 51, 53, 62-73, 83, 89, 92, 95-104 and 112-116 of instant SEQ ID NO: 13.
9. Conclusion: No claim is allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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