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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/13/2026 has been entered.
Priority
This application was filed on 09/21/2021 and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/US2020/024056 filed 03/20/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 77, 79-87, 89-102, and 112-120 are pending. Claims 77, 82, 84, 86, and 90 are amended. Claims 1-76, 78, 88-89, 103-111 are canceled. Claims 77, 79-87, 89-102, and 112-120 are being examined on the merits in this office action.
Claim Rejections - 35 USC § 112 - Withdrawn
The rejection of claims 89 and 90 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the claim amendments.
The rejection of claims 103, and 106-111 under 35 U.S.C. 102(a)(1) as being anticipated by Sidhu et al. (WO2014071234A1 – hereinafter “Sidhu”) is withdrawn in view of the canceled claims.
The rejection of claims 77, 79-87, 89-111 are rejected under 35 U.S.C. 103 as being unpatentable over Sidhu et al. (WO2014071234A1 – hereinafter “Sidhu”) in view of Johansson et al. (FEBS Letters 374 (1995) 257 261) is withdrawn in view of the claim amendments.
Claim Objections - New
Claim 79 is objected to for the following minor informality: claim 79 contains the acronym “SPR”, and an acronym in the first instance of claims should be expanded upon/spelled out with the acronym indicated in parentheses, i.e., surface plasmon resonance (SPR). The abbreviations can be used thereafter. Appropriate correction is required.
Claim Rejections - 35 USC § 103 - New
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 77, 79-87, 90-102, 112-114, and 117-120 are rejected under 35 U.S.C. 103 as being unpatentable over Sidhu et al. (WO2014071234A1 – hereinafter “Sidhu”) in view of Uppalapati et al. (US20150376604A1 – hereinafter “Uppalapati”).
Sidhu teaches a multimer GB1 peptidic compounds, comprising two or more GB 1 peptidic compounds, wherein the at least two GB1 peptidic compounds are covalently linked to each other via a linker (claims 12-14). Sidhu teaches peptidic compounds including D-peptidic compounds that specifically bind to a target molecule, that the compound may include protein domains of up to 50 residues, that the compound can be multimers that include two or more GB1 peptidic domain compounds connected via a branching moiety, that these compounds have specific binding to target molecules, that compounds can be linked via a linker (Abstract; claims 12-15). Sidhu teaches that the compound is bi-specific and that the compound has a specific binding to a target as well as a second target (Abstract; Page 27, line 1-13). Sidhu teaches that the compound has specific binding properties for two target molecules, that the compound may include two potential binding surfaces for the same target molecule, that the compound may include a first potential binding surface for a first target molecule and a second binding surface that recruits a second target molecule (Page 38, 2nd paragraph, lines 1-12). Sidhu teaches compounds may exhibit an affinity for a target protein of 1 uM or less, such as 300nM or less, 100nM or less, 30nM or less, 10nM or less, 5 nM or less, 2 nM or less, 1 nM or less, 600pM or less, 300pM or less, or even less (Page 38, 3rd paragraph, lines 1-9). Sidhu teaches that the compounds have high thermal stability with a melting temperature of 50°C or more, such as 60°C or more, 70°C or more, 80°C or more, or even 90°C or more (Page 39, line 1-3). Sidhu teaches that the compounds have low immunogenicity, e.g., are nonimmunogenic (Page 39, 3rd paragraph, line 1-2).
Sidhu does not teach that the D-domain is independently GA domain or Z domain.
Uppalapati teaches a compound that include a first potential binding surface or domain for a first target molecule and a second potential binding surface for a second target molecule [0117-0121], and that the domains include GA and Z domains (claims 1, 10, 15; [0019, 0062, 0088, 0153]). Uppalapati teaches the use of the compounds for tumor imaging [0174].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the D-protein compound of Sidhu and use GA and Z domains as taught by Uppalapati since the reference teaches a similar compound with a first and second domain for use in tumor imaging [0174]. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in modifying the teachings of Sidhu with Uppalapati since the reference teaches a similar compound with a first and second domain for binding a target protein and teaches domains such as GA and Z domains.
Regarding the limitation “wherein the compound is bivalent and has a target protein binding affinity that is at least 10- fold stronger than the target protein binding affinity of a monovalent first D-domain”, MPEP 2111.04 states: claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In the instant case, the limitation expresses the intended result of the compound of claim 77 and such a result would naturally flow. Additionally, Sidhu teaches that the compound has a binding affinity of 5 nM or less, which is consistent with the binding affinity disclosed in the instant claims and would thus read on the limitation. The disclosures render obvious claim 77.
Regarding claim 79, Sidhu teaches compounds may exhibit an affinity for a target protein of 1 uM or less, such as 300nM or less, 100nM or less, 30nM or less, 10nM or less, 5 nM or less, 2 nM or less, 1 nM or less, 600pM or less, 300pM or less, or even less (Page 38, 3rd paragraph, lines 1-9).
Regarding claim 80, Sidhu teaches that the compound binds to a target protein such as VEGF protein and that the compound is VEGF antagonist (Page 61, line 1-2; Page 74, last paragraph, line 1-4).
Regarding claims 81-82, Sidhu teaches that the compound may be dimeric or tetrameric (Page 14, 2nd paragraph, line 8-10). Sidhu teaches that the compound may comprises a first, second and third segment (Page 50, 3rd paragraph, line 3-5). Examiner notes that the disclosures read on dimeric and a third D-domain.
Regarding claims 83-84, Sidhu teaches that the compound has a binding affinity for target, non-specific binding, or bi-specific binding properties (Page 8, last paragraph, line 1-5).
Regarding claims 85-86, Sidhu teaches that the compound comprises variable scaffold domain Page 5, 1st paragraph, line 1-4), which reads on heterologous. Sidhu further teaches that scaffold domains may have the same structural motif (Page 23, 2nd paragraph, line 1-3), which reads on homologous.
Regarding claim 87, Sidhu teaches that the compound may have 54 or more residues, such as 55 or more, 56 or more, 57 or more, 58 or more, 59 or more or 60 residues or more (Page 26, line 1-2).
Regarding claim 90, Sidhu teaches that compound further comprises a linker between the at least one N-terminal peptidic extension and C-terminal peptidic extension and the GB 1 motif (Page 18, 3rd paragraph, line 1-2) and that the structural motif of GB l is characterized by a motif that includes an arrangement of four β-strands and one α-helix (Page 23, 3rd paragraph, line 1-4; page 27, last paragraph – page 28, 1st paragraph). Examiner notes that the Sidhu discloses an interhelix linker.
Regarding claims 91-92, Sidhu teaches that the compounds are optimized for binding affinity and specificity (page 38, 3rd paragraph). Sidhu teaches that the compound comprises a variable domain variable domain that is defined by a discontinuous sequence of residues may include contiguous variant amino acids at positions that are arranged close in space relative to each other in the structure of the compound, that the variable domain may form a potential binding interface of the subject compound (Page 37, 3rd paragraph, line 1-8), that the compound includes 3 or more different non-core mutations, such as, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more , 10 or more, 11 or more, or 12 or more different non-core mutations in a region outside of the β1-β2 region (Page 29, 4th paragraph, line 1-3).
Regarding claims 93-94, Sidhu teaches the use of a peptidic linker (Page 17, last paragraph, line 5; page 19, line 2-3), and further teaches non-peptidic linkers (Page 3, line 5; page 18, line 7).
Regarding claims 95-98, Sidhu teaches the compound comprises a linker between the at least one N-terminal peptidic extension and C-terminal peptidic extension and the GB 1 motif and includes amino acid residues (Page 18, 3rd paragraph, line 1-2; 4t and 5th paragraphs). Sidhu teaches L is an optional linking group wherein Lis attached to X at any convenient location (e.g., the N terminal, C-terminal or the sidechain of a surface residue not involved in binding to the target) (Page 18, line 1-5).
Regarding claims 99, Sidhu teaches that the linker may include one or more substituent groups, for example an alkyl, aryl or alkenyl group, oligo(ethylene glycol), ethers, thioethers, disulfide, amides, carbonates, carbamates, tertiary amines, alkyls, which may be straight or branched, e.g., methyl, ethyl, n-propyl, 1-methylethyl (iso-propyl), n-butyl, n-pentyl, 1, 1-dimethylethyl ( t-butyl), and the like (Page 6, 2nd paragraph, line 10-14).
Regarding claims 100, Sidhu teaches that the compounds have high thermal stability with a melting temperature of 50°C or more, such as 60°C or more, 70°C or more, 80°C or more, or even 90°C or more (Page 39, line 1-3).
Regarding claims 101, Sidhu teaches that the compound half-life can be measured in vitro or in vivo, in human blood or serum, that the compound has a half-life of 1 hour or longer, such as 2 hours or longer, 6 hours or longer, 12 hours or longer (Page 39, 2nd paragraph, line 12-16).
Regarding claim 102, Sidhu teaches that the compounds have low immunogenicity, e.g., are nonimmunogenic (Page 39, 3rd paragraph, line 1-2).
Regarding claim 113-114, Uppalapati teaches a compound that include a first potential binding surface or domain for a first target molecule and a second potential binding surface for a second target molecule, and that the domains can be for the same target molecule [0117-0121], and that the domains include GA and Z domains (claims 1, 10, 15; [0019, 0062, 0088, 0153]). It would have been obvious to modify the D-protein compound of Sidhu and use GA and Z domains and further same domains be the same as taught by Uppalapati since the reference teaches a similar compound with a first and second domain for use in tumor imaging [0174].
Regarding claim 117, Sidhu teaches that the compounds are optimized for binding affinity and specificity (page 38, 3rd paragraph). Sidhu teaches that the compounds specifically binds to a VEGF protein, such as VEGF-A, VEGF-B, VEGF-C, VEGF-D or VEGF-E, where the VEGF protein may be a synthetic D- protein or a L-protein (Page 40, 3rd paragraph).
Regarding claim 118, Sidhu teaches pharmaceutical composition comprising the compound and pharmaceutically acceptable excipients or carriers (Page 71, 2nd and 3rd paragraph).
Regarding claim 119, Sidhu teaches a method of in vivo diagnosis or imaging of a disease or condition associated with angiogenesis comprising administering to a subject the compound, wherein the disease includes cancer (claim 17; Page 52, 2nd and 3rd paragraph).
Regarding claim 120, Sidhu teaches wherein the imaging comprises PET imaging and the administering comprises administering the compound to the vascular system of the subject (claim 18).
Claim(s) 115-116 are rejected under 35 U.S.C. 103 as being unpatentable over Sidhu et al. (WO2014071234A1 – hereinafter “Sidhu”) in view of Uppalapati et al. (US20150376604A1 – hereinafter “Uppalapati”) as applied to claim 77 above, and further in view of Molnar et al. (Proc. Natl. Acad. Sci. U.S.A. 105 (30) 10483-10488).
The teachings of Sidhu and Uppalapati are disclosed and incorporated herein by reference.
Sidhu does not teach that the domains comprising specificity for binding PD-1 as recited in claims 115-116.
Molnar teaches domains that comprises a motif that is responsible for ligand binding such as PD-1 (Page 10483, left col., 1st and 2nd paragraph, line 1-20; Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of Sidhu and include a motif with a specificity to PD-1 as taught by Molnar for enhanced affinity and binding to PD-1. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in modifying Sidhu to include a motif that is specific to binding the target of interest such as PD-1, since Sidhu already teaches addition of such motif that is specific to a target protein and it would have been obvious to add a motif that is specific to PD-1 as taught by Molnar. The disclosures render obvious claims 115-116.
Response to Arguments
Applicant’s arguments, see Applicant Arguments, filed 04/13/2026, with respect to the rejection(s) of claim(s) 77, 79-87, 90-111 under 35 USC § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Uppalapati et al. and Molnar et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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