DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 5/27/26, are acknowledged.
Claims 2-9, 14, 18, 24-25 have been amended.
Claims 2-9, 14, 16-28 are pending and are under examination.
In view of Applicant’s claim amendments, only the following rejection remains. However, Applicant’s arguments relevant to the new grounds of rejection will be addressed below.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 14, 16-17 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1, from which the claims depend, requires a trimeric polypeptide with three monomers, while claims 14, 16-17 encompass a single monomer. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Applicant’s arguments filed 5/27/26 have been fully considered, but they are not persuasive.
Applicant argues that Claim 14 depends from claim 2, which requires three monomer polypeptides, and therefore incorporates all limitations of claim 2.
Claim 14 recites “at least one” monomer, and as noted by Applicant, claim 2, from which it depends, requires three monomers. Therefore, claim 14 does not require all the limitations of the claim from which it depends.
The following are new grounds of rejection necessitated by Applicant’s claim amendments.
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 2-9, 14, 16-28 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 recites that each monomer comprises 4 elements, labelled as a)-d). It is unclear what “the VL” in part b) refers to. There is no antecedent basis for “the VL”, other than the fact that an scFV, which is a separate element recited in part a), inherently would comprise a VH and a VL. Is “the VL” recited in part b) meant to be a part of the scFV in part a), or is it a separate element? In other words, does the claim require four separate elements, a)-d), wherein a) is an anti-4-BB scFV having a VH with defined CDRs and a generic VL, and part b) is another distinct VL domain, or does the claim actually require three elements, an scFV having a VH and VL region with defined CDRs, along with elements c) and d) of the claim. For the purposes of examination, the claim is being interpreted as each monomer comprises: a) an anti-4-1BB specific agonistic single-chain antibody fragment (scFv) comprising a VH and a VL with defined CDRs , b) a homotrimerization domain, and c) a polypeptide region which is capable of binding to a tumor associated antigen.
Clam 2 is also unclear since it recites an scFV wherein “the VH region which comprises a CDR1 region”. The use of “the VH region” lacks antecedent basis. While an scFV inherently has a VH and a VL, it is not clear if the intent of the claim is to define a VH of the scFV, since the use of the VH region “which” comprises a CDR1 would appear to refer to another, previously recited VH (and there is no prior recitation of a VH). In other words, it is not clear if the claim is intending to refer to a different VH “which comprises” CDRs, or whether the claim is meant to refer an scFV VH region comprising CDR1 of defined SEQ ID Nos. The same is true for the VL “which comprises”. Amendment to recite an anti-4-1BB specific agonistic scFV comprising a VH which comprises a CDR1 as defined in SEQ ID NO;1 or SEQ ID NO: 42, for example, would be remedial.
Claim 2 lacks antecedent basis for the term “the ability” in lines 9 and 15.
Claim 2 is also indefinite in that it recites a generic homotrimerization domain of, for example, collagen XVIII or those showing at least 90% with the sequence thereof. The reference to a particular percent identity in the absence of a SEQ ID NO: is unclear and indefinite. What is the identity to be compared to?.
Claim 4 is unclear since it depends from cancelled claim 1. For the purposes of examination, it is being interpreted as if it depends from claim 2.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 2-9, 14, 16-28 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. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of anti-4-1BB scFV comprising CDR functional equivalent variants showing at least 90% sequence identity with CDR SEQ ID Nos: recited in claim 2, or functional equivalent variants at least 90% identical to a collagen homotrimerization domain,
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP 2163.
The present claims are directed to a trimeric polypeptide comprising a homotrimerization domain selected from the group consisting of the collagen XVIII homotrimerization domain, the collagen XV homotrimerization domain and “a functionally equivalent variant thereof showing at least 90% identity.” The generic recitation of a collagen XVIII homotrimerization domain already would encompass a large genus of sequences, and the claims encompass 90% sequence identity to this large genus of different sequences. This would encompass polypeptides with numerous amino acid substitutions, deletions, or additions, that function in homotrimerization. Thus, the claims encompass a large genus of structurally different homotrimerization domains with distinct amino acid sequences. The state of the art is such that protein chemistry is one of the most unpredictable areas of biotechnology. Whisstock et al (Quarterly Review of Biophysics, 2003, 36, pp307-340) teach that the prediction of protein function from sequence and structure is a difficult problem, because homologous proteins often have different functions. Even single amino acid changes in a proteins amino acid sequence can have dramatic effects on protein function. For example, Wang et al., 2001, show that a single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipids growth factor receptors (e.g., abstract). These references demonstrate that even a single amino acid substitution or what appears to be an inconsequential chemical modification will often dramatically affect the biological activity and characteristic of a protein. It is noted that the claimed limitation also is new matter and therefore lacks written description for that reason as well. On page 18 the specification discloses 90% identity to SEQ ID NO: 15-18. However, the present claims are much broader and encompass at least 90% identity to a genus of other collagen XVIII or XV homotrimerization domains, which is not disclosed.
Claim 2 also encompass certain CDRs, or “functional equivalents thereof showing at least 90% identity” This would encompass a genus of different CDRs with numerous amino acid substitutions, deletions, or additions. Furthermore, the claim recites that the anti-4-1BB scFV comprises “a” functionally equivalent variant with identity to SEQ ID NO: 1 or 42, SEQ ID NO: 2 or 43 “and/”or” SEQ ID NO: 3 or SEQ ID NO: 44. The use of the “and/or” means that one could select a single element from the recited variants. In other words the claims would encompass anti-4-1BB scFV having a functionally equivalent variant CDR with 90% identity to SEQ ID NO: 3. The state of the art is such that the 6 CDRs of an antibody are critically involved in antigen binding, that even single amino acid changes can alter antigen specificity of binding, and that CDR mutations are unpredictable in terms of affinity, specificity, and solubility, and are also context dependent (see Hall, 1992, and Rabia, 2018). The specification discloses a VH CDR1 of SEQ ID NO: 1 or 42, a VH CDR2 of SEQ ID NO: 2 or 43, a VH CDR3 of SEQ ID NO: 3 or 44, a VL CDR1 of SEQ ID NO: 4 or 45, a VL CDR2 of SEQ ID NO: 5 or 46, and a VL CDR3 of SEQ ID NO: 6. This is not sufficiently representative of the genus of CDRs encompassed by the present claims. For example, the present claims encompass CDR variants with mutations, but none are disclosed.
The instant application has not provided a sufficient description showing possession of the necessary 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 genus of peptides. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Applicant’s arguments filed 5/27/26 have been fully considered, but they are not persuasive.
Applicant argues that the claims have been amended to recite at least 90% sequence identity and the ability to maintain antigen binding, and that the application on pages 15-19 discloses how to identify functionally equivalent variants of CDRs and homodimerization domains. The specification on pages 15-19 merely discloses making homodimerization variants and testing them using conventional methods in the art to asses if the functional is altered or not. This does not provide any information as to the actual structure of any working variant. No guidance is provided regarding CDR variants. The specification does not disclose any species at least 90% identical, and one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Regarding the homotrimerization domains, Applicant argues that the disclosure on page 18 provides support.
However, as noted above, page 18 discloses variants having at least 90% identity to SEQ ID NO: 15-18, and does not provide written description support for the invention as broadly claimed where the variants is at least 90% identical to any collagen XVIII or XV homotrimerization domain.
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.
Claim 2-3, 5-8, 14, 16-28 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO2019234187, in view of US 2018/0327504 and Chester, 2016.
WO2019234187 teaches a trimeric polypeptide complex comprising three monomer polypeptides wherein each monomer polypeptide comprises: a) an anti-4-1BB specific agonistic single-chain antibody fragment (scFv) b) a homotrimerization domain selected from the group consisting of the collagen XVIII homotrimerization domain (TIEXVIII), and c) a polypeptide region which is capable of specifically binding to EGRF tumor associated antigen, wherein said polypeptide region is a VHH (see pages 1-4 and 66-68, in particular). WO2019234187 teaches that the EGFR VHH is positioned C-terminal to the homotrimerization domain (See drawings). WO2019234187 teaches a polynucleotide encoding said polypeptide and a vector and host cell comprising said polynucleotide (See pages 36-40, in particular). WO2019234187 teaches a pharmaceutical composition comprising said trimeric polypeptide, and a method of treating cancer comprising administering to as subject in need thereof said trimeric polypeptide, including breast cancer, colorectal cancer, small-cell lung cancer, or EGFR+ cancers (see pages 43-47, in particular). WO2019234187 teaches using humanized antibodies and antibody fragments and that doing so reduces immunogenicity in human individuals and improves safety (See pages 24-27, in particular).
The reference differs from the claimed invention in that it does not explicitly teach a 4-1BB scFV with CDRs of claim 2, or combination with a checkpoint blocker.
The ‘504 publication teaches a 4-1BB specific humanized antibody agonist SAP3.28 with mFR2 being substituted back to murine that is potent and useful in therapeutic applications for treating cancer ((See page 1, Fig. 9). The ‘504 publication teaches that said SAP3.28 has VH CDR1-3 of SEQ ID NO: 13-15, which comprise a sequence identical to SEQ ID Nos: 42, 2, and 44, respectively, of the instant claims. The ‘504 publication teaches that the SAP3.28 has VL CDR1-4 of SEQ ID NO: 16-18, which comprise a sequence identical to SEQ ID Nos: 45, 46, and 6, of the instant claims, respectively (see Table 2, page 14, in particular). The ‘504 publication teaches that the antibodies can be in the form of an scFV and are useful in bispecific format or as a conjugate with another antibody (see page 4, in particular). The ‘504 publication teaches that the 4-1BB stimulating antibodies can be used in combination treatment with a PD-1 or PD-L1 checkpoint inhibitor antibodies (see pages 10-11, in particular).
Chester teaches that 4-1BB agonists and checkpoint blockade may represent an optimal combination that has the potential to activate anti-tumor immune effectors by complementary mechanisms, simultaneously removing the brakes and stepping on the accelerator. Chester teaches atezolizumab and pembrolizumab are promising checkpoint inhibitor antibodies.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of the ‘504 publication by using the humanized VH an VL of SAP3.28 as the VH and VL in the 4-1BB scFV in the trimer polypeptide complex of WO2019234187. One of ordinary skill in the art at the time the invention was made would have been motivated to do so, and have a reasonable expectation of success, because the ‘504 publication teaches that the human SAP3.28 antibody is a potent 4-1BB agonist that has therapeutic application in treating cancer.
Furthermore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine the trimeric polypeptide complex, with a checkpoint inhibitor, such as atezolizumab or pembrolizumab, as taught by the ‘504 publication and Chester. The ordinary artisan would have been motivated to so with a reasonable expectation of success since the ‘504 publication teaches that combining 4-1BB agonist antibodies with checkpoint inhibitors can treat cancer and Chester teaches the advantages of doing so include the potential to activate anti-tumor immune effectors by complementary mechanism, simultaneously removing the brakes and stepping on the accelerator.
Applicant’s arguments and the declaration of Inventor Compte Grau have been fully considered, but they are not persuasive.
Applicant argues that Example 6 of the specification compares the properties of the claimed anti-4-1BB scFV having defined CDRs from claim 2 and a 1D8 4-1BB derived scFV as disclosed in WO2019234187, and demonstrates improved properties.
The results are not commensurate in scope with the instant claims which encompass an enormous genus of structures. For example, a single CDR 90% identical, a genus of homotrimerization domains, any tumor binding polypeptide.
Applicant argues that converting an IgG into a functional scFV was not trivial and because of these uncertainties, one of ordinary skill in the art would not have considered the CDRs of the ‘504 publication as a suitable source of CDRs.
“Certainty” is not the requisite standard for determining obviousness. Obviousness does not require absolute predictability, only a reasonable expectation of success. The references provide a reasonable expectation of success. For example, WO2019234187 provides extensive guidance and teaches that agonistic 4-1BB antibodies can be used, wherein the VH and VL can be formatted into an scFV format. The ‘504 publication also teaches using the disclosed VH/VL in an scFV format.
Applicant argues that the declaration of Inventor Compte Grau demonstrates that an scFV from SAP3.29 shows better binding than a Fab fragment, which is unexpected.
Unexpected results requires a comparison of the claimed invention with the closest prior art. It is unclear how a comparison to a Fab is a comparison with the closes prior art, which teaches a 4-1BB scFV specifically. Furthermore, the claimed invention is to a trimeric polypeptide, and the use of an scFV is not a comparison of the claimed invention to the closest prior art. Furthermore, this would not be commensurate in scope with the instant claims for the same reasons set forth above.
Claim 4 is rejected under 35 U.S.C. 103(a) as being unpatentable over WO2019234187 and US 2018/0327504, as applied to claim 2, and further in view of Huston, 1993 and Alvarez-Cienfuegos, 2016.
The combined teachings of WO2019234187 and the ‘504 publication are discussed above.
They do not explicit teach a 4-1BB scFV encoded by SEQ ID NO: 19.
Huston teaches that scFv can be designed by linking a VH and VL via Gly4-Ser linker, and that either orientation can be used , i.e. VH-linker-VL (VH domain N-terminal to the VL domain) or VL-linker-VH (see abstract, in particular). Huston teach the linkers can be Gly4Ser repeats of 15 amino acids in length, i.e. three repeats of said Gly4Ser linker (see Table 1, in particular). See also Alvarez-Cienfuegos, which teaches scFV orientated with VH domain N-terminal to VL domain, wherein they can be trimerized with a TIE homotrimerization domain (See Fig. 1, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, to orient the scFV of the trimeric polypeptide of WO2019234187 and the ‘504 publication, using a VH-linker-VL orientation, as taught by Huston and Alvarez-Cienfuegos. Selecting from the two possible scFV orientations would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). It would also be obvious to construct the scFV using the VH and VL domains of said humanized SAP3.28 with a 15 amino acid Gly4Ser linker, since this is a known linker that can be used in scFv construction by linking a given VH and VL (see Huston and Alvarez-Cienfuegos). SEQ ID NO: 19 of the present claims encodes an scFv with the VH and VL of said humanized SAP3.28 linked via a 15 amino acid Gly4Ser linker (see the instant specification page 51, said SEQ ID NO: 19 encodes a VH domain and VL domain from humanized clone SAP3.28 with preserved murine FR3). Therefore, the cited references would render obvious an scFV encoded by SEQ ID NO: 19 by arranging the elements in the order specified above.
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.
Claim 2-8, 14, 16-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12,454,577, in view of Huston, 1993, Alvarez-Cienfuegos, 2016, 2018/0327504 and Chester, 2016.
The ‘577 patent claims a trimeric polypeptide complex comprising three monomer polypeptides comprising a homotrimerization domain of collagen XVIII and an agonist scFV of a TNFR family costimulatory receptor, and further comprising a polypeptide which binds to a tumor associated antigen at the N or C terminus of the homotrimerization domain. The ‘577 patent claims that the tumor associated antigen is EGFR and the binding agent is an anti-EGFR nanobody (i.e. a VHH). The ‘577 patent claims that the TNFR family costimulatory receptor is 4-1BB and that the agonist is an scFV. The ‘577 patent claims a polynucleotide encoding said trimeric polypeptide, vectors and host cells comprising, and methods of treating cancer, such as colorectal cancer, comprising administering said polypeptide.
Although the claimed CDRS SEQ IDs are not specifically claimed in the ‘577 patent, using a SAP3.28 scFV would be obvious based on the teachings of the ‘504 publication for the same reasons set forth above. The other claim limitations regarding VH/VL orientation, combining with a checkpoint inhibitor would be obvious in view of Huston, Alvarez-Cienfuegos, the ‘504 publication, and Chester, for the same reasons set forth above.
Applicant’s arguments filed 5/27/26 have been fully considered, but they are not persuasive.
Applicant argues that the claims are not obvious for the same reasons set forth above.
The claims stand rejected for the same reasons set forth above.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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