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 .
Priority
Priority to US 63/035,950, filed 6/8/2020, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 10/23/2023, 10/15/2024, and 8/26/2025 before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-3, 5-15, and 17-19, filed 2/3/2026, are pending. Claims 1-3, 5-15, and 17-19 are under examination.
Claim Rejections - 35 USC § 112
Claims 12, 13, and 15 were previously 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.
Response to Arguments
Applicant’s arguments, see Applicant’s Reply, page 2, para. 1, filed 2/3/2026, with respect to the rejection of claims 12, 13, and 15 under U.S.C. 112(b) have been fully considered and are persuasive. Therefore, the rejection of claims 12, 13, and 15 has been withdrawn.
Claims 12, 13, 15 and 17-19 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Response to Arguments
Applicant’s arguments, see Applicant’s Reply, page 2, para. 8, filed 2/3/2026, with respect to U.S.C. 112(a) have been fully considered and are persuasive. The rejection of claims 12, 13, 15, and 17-19 has been withdrawn.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 5-8, 12-15, and 17-19 were previously rejected under 35 U.S.C. 103 as being unpatentable over Brik et al. (Brik et al. WO 2019/234751, published 12/12/2019) in view of Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)) and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)). Claim 4 has been canceled, rendering that rejection moot.
Regarding claim 1, Brik et al. discloses cyclic polypeptides with comprising the sequences of LYLDDXiGDWWIC (SEQ ID NO: 4) and WLYLDDXiGDWWICG (SEQ ID NO: 17) (Brik et al., claims 1 and 4). Xi may be any naturally occurring amino acid. Brik et al. does not disclose the case wherein the peptide is WLYLDDCGDWWICG.
However, that position is marked as a variable position by Brik et al. claims 1 and 4. Furthermore, Dondoni discloses usage of a cysteine residue to perform a glycosylation reaction: “In conclusion, we have demonstrated that the photoinduced thiol–ene coupling (TEC) is an efficient ligation method for the site-selective glycosylation of N- and C-protected cysteine derivatives and cysteine containing peptides such as glutathione and a synthetic nonapeptide.” (Dondoni, page 11448, col. 1, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the sequences disclosed by Brik et al. with glycosylation method of Dondoni to create a peptide amenable to glycosylation by substituting the serine in position 7 of SEQ ID NO: 17 of Brik et al. with a cysteine residue. A person of ordinary skill in the art would be motivated to make such as substitution because Gunnoo discloses the following advantages of using cysteine as a modification target:
“ Another characteristic of cysteine is that it has a unique nucleophilicity, in comparison with other reactive side chains. Under physiological conditions, it has a high propensity to form the nucleophilic thiolate ion with a general pKa of 8.2. This, though, is highly dependent on its conformation and its environment in terms of buffer and neighbouring residues, and can be even lower.16, 17 As well as a unique reactivity, cysteine also has an incredibly diverse reactivity profile, as exemplified by the abundance of post-translational modifications (PTMs) it undergoes.18 It is able to interconvert between multiple oxidation states, often negates the need for co-factors in vivo, and is essential in cellular redox regulation. Cysteine is able to partake in exchange, radical and atom-, electron- and hydride-transfer reactions, and also to bind to metals.19 Its evolutionary diversity undoubtedly provides inspiration for the protein chemist developing cysteine-based methodology at the bench.” (Gunnoo, page 530, col. 2., para. 3).
Consequently, a person of ordinary skill in the art attempting to modify SEQ ID NO: 17 of Brik et al. to gain the cysteine-based advantages disclosed by Gunnoo would have a reasonable expectation of success by modifying the peptide at this position. Such a modification would result in SEQ ID NO: 13 of the current application. Consequently, claim 1 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 further recites the case wherein the cysteine residue at position 7 of SEQ ID NO: 13 comprises a chemical modification. As disclosed by Dondoni (Dondoni et al., page 11445, Scheme 1) and Gunnoo (Gunnoo et al., page 531, col. 1, para. 2), cysteine is the target of chemical modification reactions. Consequently, claim 2 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 3, claim 2 is rejected as described above. Claim 3 further recites the case wherein the chemical modification is selected from alkylation, arylation, oxidation. Gunnoo discloses the case wherein the chemical modification is alkylation (Gunnoo et al., page 531, col. 1, para. 2). Consequently, claim 3 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 4, claim 1 is rejected as described above. Claim 4 further recites the case wherein the peptide is at most 16 amino acids. SEQ ID NO: 17 of Brik et al. is 14 amino acids in length. Consequently, claim 4 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 5, claim 1 is rejected as described above. Claim 5 further recites the case wherein the amino acid at position one of the N terminus is a D amino acid. Claim 11 of Brik et al. discloses the case wherein the amino acid at position one is a D amino acid. Consequently, claim 5 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 6, claim 1 is rejected as described above. Claim 6 further recites the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Claim 12 of Brik et al. discloses the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Consequently, claim 6 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 7, claim 1 is rejected as described above. Claim 7 further recites the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Claim 13 of Brik et al. discloses the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Consequently, claim 7 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 8, claim 7 is rejected as described above. Claim 8 further recites the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2SAc. Claim 14 of Brik et al. discloses the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2Sac. Consequently, claim 8 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 12, claim 1 is rejected as described above. Claim 12 further recites the case wherein the cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, or both. Claim 15 of Brik et al. discloses the case wherein said cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, or any combination thereof. Consequently, claim 12 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 13, claim 1 is rejected as described above. Claim 13 further recites the case wherein the binding affinity Kd for ubiquitin is 0.05-100 nM. Claim 17 of Brik et al. discloses “…and optionally wherein said increased affinity is binding affinity KD of 0.05-100 nM.”.
Consequently, claim 13 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 14, claim 1 is rejected as described above. Claim 14 further recites an acceptable carrier. Claim 18 of Brik et al. discloses: ” A composition comprising the cyclic polypeptide of any one of claims 1 to 17 and at least one acceptable carrier or diluent.” Consequently, claim 14 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 15, claim 14 is rejected as described above. Claim further recites the case wherein the pharmaceutical composition is characterized by pro-apoptotic activity. The structure referenced by claim 15 is obvious for the reasons stated above. MPEP 2112.01(II) states: “A chemical composition and its properties are inseparable.” Consequently, claim 15 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 17, claim 14 is rejected as described above. Claim 17 further recites a method for treating a subject afflicted with cancer, comprising administering to said subject a therapeutically effective amount of the pharmaceutical composition of claim 14, thereby treating the subject afflicted with cancer.
Claim 20 of Brik et al. discloses: “ A method for ameliorating or treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a cyclic polypeptide, wherein said polypeptide binds ubiquitin with an affinity KD of 0.05-100 nM, wherein said cyclic polypeptide comprises not more than 16 amino acid residues, and wherein at least 55% of amino acids of said cyclic polypeptide are selected from the group consisting of: W, G, F, D, L, Y and C.” Consequently, claim 17 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 18, claim 17 is rejected as described above. Claim 18 further recites the case wherein treating comprises reducing deubiquitination activity of at least one cell of said subject. Claim 35 of Brik et al. discloses: The method of any one of claims 19 to 34, wherein said cyclic polypeptide reduces deubiquitination activity of a cell by at least 30%.”. Consequently, claim 18 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 19, claim 17 is rejected as described above. Claim 19 further recites the case wherein treating comprises reducing ubiquitinated proteins proteasomal rate in at least one cell of the subject. Claim 36 of Brik et al. discloses: “The method of claim 35, wherein said cyclic polypeptide reduces ubiquitinated proteins proteasomal degradation rate by at least 40%.” Consequently, claim 18 is obvious over Brik et al. in view of Dondoni et al. and Gunnoo et al. and rejected.
Claims 1-3, 5-8, 12-15, and 17-19 were previously rejected under 35 U.S.C. 103 as being unpatentable over Brik et al. 2 (U.S. Patent No. 12,084,523) in view of Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)) and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)). Claim 4 has been canceled, rendering that rejection moot.
Regarding claim 1, Brik et al. 2 discloses cyclic polypeptides with comprising the sequences of LYLDDXiGDWWIC (SEQ ID NO: 4) and WLYLDDSGDWWICG (SEQ ID NO: 17) (Brik et al. 2, claims 1 and 4). Xi may be any naturally occurring amino acid. Brik et al. 2 does not disclose the case wherein the peptide is WLYLDDCGDWWICG.
However, that position is marked as a variable position by Brik et al. 2 claim 1. Furthermore, Dondoni discloses usage of a cysteine residue to perform a glycosylation reaction: “In conclusion, we have demonstrated that the photoinduced thiol–ene coupling (TEC) is an efficient ligation method for the site-selective glycosylation of N- and C-protected cysteine derivatives and cysteine containing peptides such as glutathione and a synthetic nonapeptide.” (Dondoni, page 11448, col. 1, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the sequences disclosed by Brik et al. 2 with glycosylation method of Dondoni to create a peptide amenable to glycosylation by substituting the serine in position 7 of SEQ ID NO: 17 of Brik et al. 2 with a cysteine residue. A person of ordinary skill in the art would be motivated to make such as substitution because Gunnoo discloses the following advantages of using cysteine as a modification target:
“ Another characteristic of cysteine is that it has a unique nucleophilicity, in comparison with other reactive side chains. Under physiological conditions, it has a high propensity to form the nucleophilic thiolate ion with a general pKa of 8.2. This, though, is highly dependent on its conformation and its environment in terms of buffer and neighbouring residues, and can be even lower.16, 17 As well as a unique reactivity, cysteine also has an incredibly diverse reactivity profile, as exemplified by the abundance of post-translational modifications (PTMs) it undergoes.18 It is able to interconvert between multiple oxidation states, often negates the need for co-factors in vivo, and is essential in cellular redox regulation. Cysteine is able to partake in exchange, radical and atom-, electron- and hydride-transfer reactions, and also to bind to metals.19 Its evolutionary diversity undoubtedly provides inspiration for the protein chemist developing cysteine-based methodology at the bench.” (Gunnoo, page 530, col. 2., para. 3).
Brik et al. 2 also has this position marked as a variable position as disclosed in claim 1. Consequently, a person of ordinary skill in the art attempting to modify SEQ ID NO: 17 to gain the cysteine-based advantages disclosed by Gunnoo of Brik et al. 2 would have a reasonable expectation of success by modifying the peptide at this position. Such a modification would result in SEQ ID NO: 13 of the current application. Consequently, claim 1 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 further recites the case wherein the cysteine residue at position 7 of SEQ ID NO: 13 comprises a chemical modification. As disclosed by Dondoni (Dondoni et al., page 11445, Scheme 1) and Gunnoo (Gunnoo et al., page 531, col. 1, para. 2), cysteine is the target of chemical modification reactions. Consequently, claim 2 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 3, claim 2 is rejected as described above. Claim 3 further recites the case wherein the chemical modification is selected from alkylation, arylation, oxidation. Gunnoo discloses the case wherein the chemical modification is alkylation (Gunnoo et al., page 531, col. 1, para. 2). Consequently, claim 3 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 5, claim 1 is rejected as described above. Claim 5 further recites the case wherein the amino acid at position one of the N terminus is a D amino acid. Claim 7 of Brik et al. 2 discloses the case wherein position one is a D amino acid. Consequently, claim 5 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 6, claim 1 is rejected as described above. Claim 6 further recites the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Claim 8 of Brik et al. 2 discloses the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Consequently, claim 6 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 7, claim 1 is rejected as described above. Claim 7 further recites the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Claim 8 of Brik et al. 2 discloses the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Consequently, claim 7 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 8, claim 7 is rejected as described above. Claim 8 further recites the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2SAc. Claim 8 of Brik et al. 2 discloses the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2Sac. Consequently, claim 8 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 12, claim 1 is rejected as described above. Claim 12 further recites the case wherein the cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, or both. Claim 9 of Brik et al. 2 discloses the case wherein said cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, increased affinity to Ub compared to control, or any combination thereof. Consequently, claim 12 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 13, claim 1 is rejected as described above. Claim 13 further recites the case wherein the binding affinity Kd for ubiquitin is 0.05-100 nM. Claim 9 of Brik et al. 2 discloses “…and optionally wherein said increased affinity is binding affinity KD of 0.05-100 nM.”.
Consequently, claim 13 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 14, claim 1 is rejected as described above. Claim 14 further recites an acceptable carrier. Claim 10 of Brik et al. 2 discloses” A composition comprising the cyclic polypeptide of claim 1, and at least one acceptable carrier or diluent.” Consequently, claim 14 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 15, claim 14 is rejected as described above. Claim further recites the case wherein the pharmaceutical composition is characterized by pro-apoptotic activity. The structure referenced by claim 15 is obvious for the reasons stated above. MPEP 2112.01(II) states: “A chemical composition and its properties are inseparable.” Consequently, claim 15 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 17, claim 14 is rejected as described above. Claim 17 further recites a method for treating a subject afflicted with cancer, comprising administering to said subject a therapeutically effective amount of the pharmaceutical composition of claim 14, thereby treating the subject afflicted with cancer.
Claim 11 of Brik et al. 2 discloses: “A method for ameliorating or treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the cyclic polypeptide of claim 1.” Consequently, claim 17 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 18, claim 17 is rejected as described above. Claim 18 further recites the case wherein treating comprises reducing deubiquitination activity of at least one cell of said subject. Claim 12 of Brik et al. 2 discloses: “…(xiv) said cyclic polypeptide reduces deubiquitination activity of a cell by at least 30%;…”. Consequently, claim 18 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 19, claim 17 is rejected as described above. Claim 19 further recites the case wherein treating comprises reducing ubiquitinated proteins proteasomal rate in at least one cell of the subject. Claim 12 of Brik et al. 2 discloses: “…(xv) said cyclic polypeptide reduces ubiquitinated proteins proteasomal degradation rate by at least 40%;…” Consequently, claim 18 is obvious over Brik et al. 2 in view of Dondoni et al. and Gunnoo et al. and rejected.
Claims 1-3, 5-8, 12-15, and 17-19 were previously rejected under 35 U.S.C. 103 as being unpatentable over Brik et al. 3 (U.S. Patent No. 11,639,369) in view of Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)) and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)). Claim 4 has been canceled, rendering that rejection moot.
Regarding claim 1, Brik et al. 3 discloses cyclic polypeptides with comprising the sequences of LYLDDXiGDWWIC (SEQ ID NO: 4) and WLYLDDSGDWWICG (SEQ ID NO: 17) (Brik et al. 3, page 46, col. 2, line 10). Xi may be any naturally occurring amino acid. Brik et al. 3 does not disclose the case wherein the peptide is WLYLDDCGDWWICG.
However, that position is marked as a variable position by Brik et al. 3 (Brik et al. 3, page 46, col. 2, line 10). Furthermore, Dondoni discloses usage of a cysteine residue to perform a glycosylation reaction: “In conclusion, we have demonstrated that the photoinduced thiol–ene coupling (TEC) is an efficient ligation method for the site-selective glycosylation of N- and C-protected cysteine derivatives and cysteine containing peptides such as glutathione and a synthetic nonapeptide.” (Dondoni, page 11448, col. 1, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the sequences disclosed by Brik et al. 3 with glycosylation method of Dondoni to create a peptide amenable to glycosylation by substituting the serine in position 7 of SEQ ID NO: 17 of Brik et al. 3 with a cysteine residue. A person of ordinary skill in the art would be motivated to make such as substitution because Gunnoo discloses the following advantages of using cysteine as a modification target:
“ Another characteristic of cysteine is that it has a unique nucleophilicity, in comparison with other reactive side chains. Under physiological conditions, it has a high propensity to form the nucleophilic thiolate ion with a general pKa of 8.2. This, though, is highly dependent on its conformation and its environment in terms of buffer and neighbouring residues, and can be even lower.16, 17 As well as a unique reactivity, cysteine also has an incredibly diverse reactivity profile, as exemplified by the abundance of post-translational modifications (PTMs) it undergoes.18 It is able to interconvert between multiple oxidation states, often negates the need for co-factors in vivo, and is essential in cellular redox regulation. Cysteine is able to partake in exchange, radical and atom-, electron- and hydride-transfer reactions, and also to bind to metals.19 Its evolutionary diversity undoubtedly provides inspiration for the protein chemist developing cysteine-based methodology at the bench.” (Gunnoo, page 530, col. 2., para. 3).
Brik et al. 3 also has this position marked as a variable position as disclosed in claim 1. Consequently, a person of ordinary skill in the art attempting to modify SEQ ID NO: 17 to gain the cysteine-based advantages disclosed by Gunnoo of Brik et al. 3 would have a reasonable expectation of success by modifying the peptide at this position. Such a modification would result in SEQ ID NO: 13 of the current application. Consequently, claim 1 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 further recites the case wherein the cysteine residue at position 7 of SEQ ID NO: 13 comprises a chemical modification. As disclosed by Dondoni (Dondoni et al., page 11445, Scheme 1) and Gunnoo (Gunnoo et al., page 531, col. 1, para. 2), cysteine is the target of chemical modification reactions. Consequently, claim 2 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 3, claim 2 is rejected as described above. Claim 3 further recites the case wherein the chemical modification is selected from alkylation, arylation, oxidation. Gunnoo discloses the case wherein the chemical modification is alkylation (Gunnoo et al., page 531, col. 1, para. 2). Consequently, claim 3 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 5, claim 1 is rejected as described above. Claim 5 further recites the case wherein the amino acid at position one of the N terminus is a D amino acid. Claim 4 of Brik et al. 3 discloses the case wherein position one is a D amino acid. Consequently, claim 5 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 6, claim 1 is rejected as described above. Claim 6 further recites the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Claim 5 of Brik et al. 3 discloses the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Consequently, claim 6 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 7, claim 1 is rejected as described above. Claim 7 further recites the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Claim 5 of Brik et al. 3 discloses the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Consequently, claim 7 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 8, claim 7 is rejected as described above. Claim 8further recites the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2SAc. Claim 5 of Brik et al. 3 discloses the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2Sac. Consequently, claim 8 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 12, claim 1 is rejected as described above. Claim 12 further recites the case wherein the cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, or both. Claim 6 of Brik et al. 3 discloses the case wherein said cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, increased affinity to Ub compared to control, or any combination thereof. Consequently, claim 12 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 13, claim 1 is rejected as described above. Claim 13 further recites the case wherein the binding affinity Kd for ubiquitin is 0.05-100 nM. Claim 6 of Brik et al. 3 discloses “…and optionally wherein said increased affinity is binding affinity KD of 0.05-100 nM.”.
Consequently, claim 13 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 14, claim 1 is rejected as described above. Claim 14 further recites an acceptable carrier. Claim 7 of Brik et al. 3 discloses” A composition comprising the cyclic polypeptide of claim 1, and at least one acceptable carrier or diluent.” Consequently, claim 14 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 15, claim 14 is rejected as described above. Claim further recites the case wherein the pharmaceutical composition is characterized by pro-apoptotic activity. The structure referenced by claim 15 is obvious for the reasons stated above. MPEP 2112.01(II) states: “A chemical composition and its properties are inseparable.” Consequently, claim 15 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 17, claim 14 is rejected as described above. Claim 17 further recites a method for treating a subject afflicted with cancer, comprising administering to said subject a therapeutically effective amount of the pharmaceutical composition of claim 14, thereby treating the subject afflicted with cancer.
Claim 8 of Brik et al. 3 discloses: “A method for ameliorating or treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the cyclic polypeptide of claim 1.” Consequently, claim 17 is obvious over Brik et al. 3 in view of Dondoni et al. and Gunnoo et al. and rejected.
Response to Arguments
Applicant's arguments filed 2/3/2026 have been fully considered but they are not persuasive.
Applicant asserts that logic used in the combination of Brik et al., Brik et al. 2, Brik et al. 3 with Dondoni et al. and Gunnoo et al. involves impermissible hindsight reasoning (Applicant Reply, page 6, para. 6).
Applicant asserts that Dondoni and Gunnoo are related to glycosylation, not ubiquitin binding (Applicant Reply page 6 para. 7 and page 7 para. 1-2). However, glycosylation of the peptide of Brik, Brik 2, or Brik 3 is a valid motivation for such a modification.
MPEP 2144(IV) states: “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).”
In this case, that different purpose is making the peptide of Brik, Brik 2, or Brik 3 amenable to glycosylation and further work or experiments that may require such a molecule.
Regarding Applicant’s assertion about “obvious to try” rationale (Applicant Reply, page 7, para. 4), the purpose of Dondoni and Gunnoo were to provide rationale for selecting cysteine at that position. No “obvious to try” argument was invoked regarding this substitution.
Regarding Applicant’s assertion that position 7 is not a valid substitution target (Applicant Reply, page 8, para. 1), Brik, Brik 2, and Brik 3 specifically denote position 7 as a variable position. Dondoni and Gunnoo provide the motivation to substitute a cysteine and the position marked variable in the sequences of Brik, Brik 2, and Brik 3. Cysteine is not excluded by Brik, Brik 2, or Brik 3 and therefore a reasonable expectation of success exists because this is denoted as a variable position.
New Rejections-35 USC § 103
Claims 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Brik et al. (Brik et al. WO 2019/234751, published 12/12/2019) in view of Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)) and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)), as applied to claim 1 above, further in view of Vadas et al. (Vadas, et al. Journal of peptide science: an official publication of the European Peptide Society 13.9: 581-587 (2007)).
Regarding claim 9, claim 1 is obvious as described above. Brik, Dondoni, and Gunnoo do not explicitly disclose a dimer.
However, Vadas et al. discloses that: “Multivalency has advantages over monovalency for binding interactions and even for activity. In particular, avidity is higher since the off-rate of a multivalent species is much slower than that of a monomer.” (Vadas, et al., Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to create a homodimer as suggested by Vadas of the peptide disclosed by Brik, Dondoni, and Gunnoo to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the dimer suggested by Vadas in order to achieve the superior avidity effects. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Brik, Dondoni, and Gunnoo binds ubiquitin and would be expected to benefit from the avidity effect described by Vadas.
Consequently, claim 9 is obvious over Brik et al., Dondoni et al., and Gunnoo et al. as applied to claim 1, further in view of Vadas and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the dimer is a homodimer. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a homodimer in order to duplicate the binding effect of the monomer and benefit from avidity as described by Vadas.
Consequently, claim 10 is obvious over Brik et al., Dondoni et al., and Gunnoo et al. as applied to claim 1, further in view of Vadas et al. and rejected.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Brik et al. (Brik et al. WO 2019/234751, published 12/12/2019) in view of Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)), Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)), and Vadas et al. (Vadas, et al. Journal of peptide science: an official publication of the European Peptide Society 13.9: 581-587 (2007)) as applied to claim 9 above, further in view of Annis et al. (Annis, et al. Methods in enzymology 289 198-221. (1997)).
Regarding claim 11, claim 9 is obvious as described above. Claim 11 further recites the case wherein the homodimer is formed through cysteine linkages. Brik, Dondoni, Gunnoo, and Vadas do not explicitly disclose cysteine linkages.
However, Annis discloses that disulfide bonds through cysteine residues can be used to form both parallel and anti-parallel homodimers:
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231
421
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(Annis et al., page 201, Scheme 3)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to create a homodimer as suggested by Vadas of the peptide disclosed by Brik, Dondoni, and Gunnoo using disulfide bonds through cysteine residues as disclosed by Annis to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to form the dimer suggested by Brik, Dondoni, Gunnoo, and Vadas in order to achieve the superior avidity effects. A person of ordinary skill in the art would have a reasonable expectation of success using the scheme of Annis because Annis discloses detailed procedures for forming such disulfide bonds (Annis et al., pages 207-221)
Consequently, claim 11 is obvious over Brik et al., Dondoni et al., Gunnoo et al., and Vadas et al. as applied to claim 9, further in view of Annis et al. and rejected.
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.
Claims 1-3, 5-8, 12-15, and 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 12,084,523, in view of Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)) and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)). Claim 4 has been canceled, rendering that rejection moot.
Regarding claim 1, the ‘523 patent discloses cyclic polypeptides with comprising the sequences of LYLDDXiGDWWIC (SEQ ID NO: 4) and WLYLDDSGDWWICG (SEQ ID NO: 17) (‘523 patent, claims 1 and 4). Xi may be any naturally occurring amino acid. The ‘523 patent does not disclose the case wherein the peptide is WLYLDDCGDWWICG.
However, that position is marked as a variable position by ‘523 claim 1. Furthermore, Dondoni discloses usage of a cysteine residue to perform a glycosylation reaction: “In conclusion, we have demonstrated that the photoinduced thiol–ene coupling (TEC) is an efficient ligation method for the site-selective glycosylation of N- and C-protected cysteine derivatives and cysteine containing peptides such as glutathione and a synthetic nonapeptide.” (Dondoni, page 11448, col. 1, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the sequences disclosed by the ‘523 patent with glycosylation method of Dondoni to create a peptide amenable to glycosylation by substituting the serine in position 7 of SEQ ID NO: 17 of the ‘523 patent with a cysteine residue. A person of ordinary skill in the art would be motivated to make such as substitution because Gunnoo discloses the following advantages of using cysteine as a modification target:
“ Another characteristic of cysteine is that it has a unique nucleophilicity, in comparison with other reactive side chains. Under physiological conditions, it has a high propensity to form the nucleophilic thiolate ion with a general pKa of 8.2. This, though, is highly dependent on its conformation and its environment in terms of buffer and neighbouring residues, and can be even lower.16, 17 As well as a unique reactivity, cysteine also has an incredibly diverse reactivity profile, as exemplified by the abundance of post-translational modifications (PTMs) it undergoes.18 It is able to interconvert between multiple oxidation states, often negates the need for co-factors in vivo, and is essential in cellular redox regulation. Cysteine is able to partake in exchange, radical and atom-, electron- and hydride-transfer reactions, and also to bind to metals.19 Its evolutionary diversity undoubtedly provides inspiration for the protein chemist developing cysteine-based methodology at the bench.” (Gunnoo, page 530, col. 2., para. 3).
The ’523 patent also has this position marked as a variable position as disclosed in claim 1. Consequently, a person of ordinary skill in the art attempting to modify SEQ ID NO: 17 to gain the cysteine-based advantages disclosed by Gunnoo of the ‘523 patent would have a reasonable expectation of success by modifying the peptide at this position. Such a modification would result in SEQ ID NO: 13 of the current application. Consequently, claim 1 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 2, claim 1 is rejected as described above. Claim 2 further recites the case wherein the cysteine residue at position 7 of SEQ ID NO: 13 comprises a chemical modification. As disclosed by Dondoni (Dondoni et al., page 11445, Scheme 1) and Gunnoo (Gunnoo et al., page 531, col. 1, para. 2), cysteine is the target of chemical modification reactions. Consequently, claim 2 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 3, claim 2 is rejected as described above. Claim 3 further recites the case wherein the chemical modification is selected from alkylation, arylation, oxidation. Gunnoo discloses the case wherein the chemical modification is alkylation (Gunnoo et al., page 531, col. 1, para. 2). Consequently, claim 3 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 5, claim 1 is rejected as described above. Claim 5 further recites the case wherein the amino acid at position one of the N terminus is a D amino acid. Claim 7 of the ‘523 patent discloses the case wherein position one is a D amino acid. Consequently, claim 5 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 6, claim 1 is rejected as described above. Claim 6 further recites the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Claim 8 of the ‘523 patent discloses the case wherein the amino acid at position one of the N terminus is conjugated to a cyclizing molecule. Consequently, claim 6 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 7, claim 1 is rejected as described above. Claim 7 further recites the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Claim 8 of the ‘523 patent discloses the case wherein the cyclic peptide is prepared using a cyclizing molecule comprising a halogen. Consequently, claim 7 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 8, claim 7 is rejected as described above. Claim 8 further recites the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2SAc. Claim 8 of the ‘523 patent discloses the case wherein said cyclizing molecule is selected from the group consisting of: chloracetyl chloride, 3-chlorobenzoyl (3-ClBz), 4-chlorobenzoyl (4-ClBz) or Cl2Sac. Consequently, claim 8 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 12, claim 1 is rejected as described above. Claim 12 further recites the case wherein the cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, or both. Claim 9 of the ‘523 patent discloses the case wherein said cyclic polypeptide is characterized as having: cell penetration capability, ubiquitin (Ub) binding capability, increased affinity to Ub compared to control, or any combination thereof. Consequently, claim 12 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 13, claim 1 is rejected as described above. Claim 13 further recites the case wherein the binding affinity Kd for ubiquitin is 0.05-100 nM. Claim 9 of the ‘523 patent discloses “…and optionally wherein said increased affinity is binding affinity KD of 0.05-100 nM.”.
Consequently, claim 13 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 14, claim 1 is rejected as described above. Claim 14 further recites an acceptable carrier. Claim 10 of the ‘523 patent discloses” A composition comprising the cyclic polypeptide of claim 1, and at least one acceptable carrier or diluent.” Consequently, claim 14 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 15, claim 14 is rejected as described above. Claim further recites the case wherein the pharmaceutical composition is characterized by pro-apoptotic activity. The structure referenced by claim 15 is obvious for the reasons stated above. MPEP 2112.01(II) states: “A chemical composition and its properties are inseparable.” Consequently, claim 15 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 17, claim 14 is rejected as described above. Claim 17 further recites a method for treating a subject afflicted with cancer, comprising administering to said subject a therapeutically effective amount of the pharmaceutical composition of claim 14, thereby treating the subject afflicted with cancer.
Claim 11 of the ‘523 patent discloses: “A method for ameliorating or treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the cyclic polypeptide of claim 1.” Consequently, claim 17 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 18, claim 17 is rejected as described above. Claim 18 further recites the case wherein treating comprises reducing deubiquitination activity of at least one cell of said subject. Claim 12 of the ‘523 patent discloses: “…(xiv) said cyclic polypeptide reduces deubiquitination activity of a cell by at least 30%;…”. Consequently, claim 18 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Regarding claim 19, claim 17 is rejected as described above. Claim 19 further recites the case wherein treating comprises reducing ubiquitinated proteins proteasomal rate in at least one cell of the subject. Claim 12 of the ‘523 patent discloses: “…(xv) said cyclic polypeptide reduces ubiquitinated proteins proteasomal degradation rate by at least 40%;…” Consequently, claim 18 is obvious over the ’523 patent in view of Dondoni et al. and Gunnoo et al. and rejected.
Response to Arguments
Applicant's arguments filed 2/3/2026 have been fully considered but they are not persuasive.
Applicant asserts that logic used in the combination of Brik et al., Brik et al. 2, Brik et al. 3 with Dondoni et al. and Gunnoo et al. involves impermissible hindsight reasoning (Applicant Reply, page 6, para. 6) and then applies the same logic to the nonstatutory double patenting rejection (Applicant Reply, page 8, para. 6).
Applicant asserts that Dondoni and Gunnoo are related to glycosylation, not ubiquitin binding (Applicant Reply page 6 para. 7 and page 7 para. 1-2). However, glycosylation of the peptide of Brik, Brik 2, or Brik 3 is a valid motivation for such a modification.
MPEP 2144(IV) states: “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).”
In this case, that different purpose is making the peptide of Brik, Brik 2, or Brik 3 amenable to glycosylation and further work or experiments that may require such a molecule.
Regarding Applicant’s assertion about “obvious to try” rationale (Applicant Reply, page 7, para. 4), the purpose of Dondoni and Gunnoo were to provide rationale for selecting cysteine at that position. No “obvious to try” argument was invoked regarding this substitution.
Regarding Applicant’s assertion that position 7 is not a valid substitution target (Applicant Reply, page 8, para. 1), Brik, Brik 2, and Brik 3 specifically denote position 7 as a variable position. Dondoni and Gunnoo provide the motivation to substitute a cysteine and the position marked variable in the sequences of Brik, Brik 2, and Brik 3. Cysteine is not excluded by Brik, Brik 2, or Brik 3 and therefore a reasonable expectation of success exists because this is denoted as a variable position.
Double Patenting-New Rejections
Claims 9 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 12,084,523, Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)), and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)) as applied to claim 1 above, further in view of Vadas et al. (Vadas, et al. Journal of peptide science: an official publication of the European Peptide Society 13.9: 581-587 (2007)).
Regarding claim 9, claim 1 is obvious as described above. The ‘523 patent, Dondoni, and Gunnoo do not explicitly disclose a dimer.
However, Vadas et al. discloses that: “Multivalency has advantages over monovalency for binding interactions and even for activity. In particular, avidity is higher since the off-rate of a multivalent species is much slower than that of a monomer.” (Vadas, et al., Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to create a homodimer as suggested by Vadas of the peptide disclosed by the ‘523 patent, Dondoni, and Gunnoo to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the dimer suggested by Vadas in order to achieve the superior avidity effects. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of the ‘523 patent, Dondoni, and Gunnoo binds ubiquitin and would be expected to benefit from the avidity effect described by Vadas.
Consequently, claim 9 is obvious over the ‘523 patent, Dondoni et al., and Gunnoo et al. as applied to claim 1, further in view of Vadas and rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 10 further recites the case wherein the dimer is a homodimer. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize a homodimer in order to duplicate the binding effect of the monomer and benefit from avidity as described by Vadas.
Consequently, claim 10 is obvious over the ‘523 patent, Dondoni et al., and Gunnoo et al. as applied to claim 1, further in view of Vadas et al. and rejected.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over claims 1 and 4 of U.S. Patent No. 12,084,523, Dondoni et al. (Dondoni, et al. Chemistry–A European Journal 15.43: 11444-11449 (2009)), and Gunnoo et al. (Gunnoo, et al. ChemBioChem 17.7: 529-553 (2016)) Vadas et al. (Vadas, et al. Journal of peptide science: an official publication of the European Peptide Society 13.9: 581-587 (2007)) as applied to claim 9 above, further in view of Annis et al. (Annis, et al. Methods in enzymology 289 198-221. (1997)).
Regarding claim 11, claim 9 is obvious as described above. Claim 11 further recites the case wherein the homodimer is formed through cysteine linkages. The ‘523 patent, Dondoni, Gunnoo, and Vadas do not explicitly disclose cysteine linkages.
However, Annis discloses that disulfide bonds through cysteine residues can be used to form both parallel and anti-parallel homodimers:
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231
421
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(Annis et al., page 201, Scheme 3)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to create a homodimer as suggested by Vadas of the peptide disclosed by the ‘523 patent, Dondoni, and Gunnoo using disulfide bonds through cysteine residues as disclosed by Annis to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to form the dimer suggested by the ‘523 patent, Dondoni, Gunnoo, and Vadas in order to achieve the superior avidity effects. A person of ordinary skill in the art would have a reasonable expectation of success using the scheme of Annis because Annis discloses detailed procedures for forming such disulfide bonds (Annis et al., pages 207-221)
Consequently, claim 11 is obvious over the ‘523 patent, Dondoni et al., Gunnoo et al., and Vadas et al. as applied to claim 9, further in view of Annis et al. and rejected.
Conclusion
Claims 1-3, 5-15, and 17-19 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
