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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/9/2026 has been entered.
Priority
Priority to US application 62/963,260, filed 1/20/2020, is acknowledged.
Information Disclosure Statement
No information disclosure statement has been filed at this time.
Claim Status
Claims 1, 3-6, 9, 11-16, 18, and 20-27 from the 3/9/2026 submission are pending in this application. Claims 2, 7, 8, 10, 17, and 19 are canceled. Claims 1, 3-6, 9, 11-16, 18, and 26-27 are under examination. Claims 20-25 are currently withdrawn.
Claim Interpretation
Regarding claim 1 and 11, these claims have been amended to recite the transitional phrase “consisting essentially of”.
MPEP 2111.03(III) states: “For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355.” and “ If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of "consisting essentially of," applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of the claimed invention. In re De Lajarte, 337 F.2d 870, 143 USPQ 256 (CCPA 1964)”
Consequently, these claims are interpreted to encompass any number of additional amino acids. It is unpredictable which amino acids would materially affect basic and novel characteristics of the invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Maintained Rejections
Claims 1, 3-6, 9, 11-16, and 18 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 claims contain 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.
Regarding claim 1, claim 1 recites “a conjugated peptide with affinity for or targeted to Akt consisting essentially of a peptide according to SEQ ID NO: 1 conjugated to an antioxidant moiety, wherein the conjugated peptide inhibits protein oxidation of the targeted Akt protein.” As discussed above in claim interpretation, this claim encompasses a peptide of any sequence and any length which covers unlimited sequence space. Even if taken as a 20-mer peptide, this would be 20^15 sequences.
In this case, 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 inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), a "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Claim 1 contains no limitations on the peptide that effectively reduce the claimed sequence space that is conjugated to an antioxidant moiety. Consequently, the claim is extremely broad.
MPEP § 2163 (II.A.3.a.ii.) states that “for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
In the instant case, Applicant reduces three peptides to practice. At the time the invention was made, the level of skill for preparing and screening polypeptides with desired functional properties was high. However, even if a synthesis and selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify polypeptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally.
Applicant discloses SEQ ID NOs: 1, 2, and 3. SEQ ID NO: 1 is five residues and SEQ ID NOs: 2 and 3 are both 13 residues. SEQ ID NO: 1 contains serine residues while SEQ ID NOs: 2 and 3 do not.
Claim 1 now recites that the peptide consists essentially of SEQ ID NO: 1. There is still no defined limit on how many sequences this claim encompasses. The provided specification only reduces one peptide to practice that comprises SEQ ID NO: 1. Consequently, the mathematics for the number of claimed sequences described above still applies.
The provided examples only represent a limited structural diversity. Since only a limited number of species of peptides are taught within the claimed genus above, the instant claim above fails the written description requirement. A representative number of species has not been taught to describe this genus. Regarding the peptides, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 1. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 1 is rejected.
Regarding claim 3, claim 1 is rejected as described above. Claim 3 only provides a functional limitation, not a structural limitation. MPEP 2112.01(II) recites: “"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”. Some members of the sequence space disclosed by claim 1 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 3 is rejected.
Regarding claim 4, claim 1 is rejected as described above. Claim 4 defines the antioxidant moiety, but does not reduce the size of the genus of the claimed peptide. Consequently, claim 4 is rejected.
Regarding claim 5, claim 1 is rejected as described above. Claim 5 only provides a functional limitation, not a structural limitation. MPEP 2112.01(II) recites: “"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”. Some members of the sequence space disclosed by claim 1 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 5 is rejected.
Regarding claim 6, claim 5 is rejected as described above. Claim 6 recites further functional limitations but not structural limitations. Some members of the sequence space disclosed by claim 5 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 6 is rejected.
Regarding claim 9, claim 1 is rejected as described above. Claim 9 only provides a functional limitation, not a structural limitation. MPEP 2112.01(II) recites: “"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”. Some members of the sequence space disclosed by claim 1 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 9 is rejected.
Regarding claim 11, claim 11 possesses the same scope of sequence space as claim 1. No additional representative species exist for this claim. Therefore, one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 11. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 11 is rejected.
Regarding claim 12, claim 11 is rejected as described above. Claim 12 only provides a functional limitation, not a structural limitation. MPEP 2112.01(II) recites: “"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”. Some members of the sequence space disclosed by claim 12 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus.
Regarding claim 13, claim 11 is rejected as described above. Claim 13 does not reduce the size of the genus of the claimed peptide. Consequently, claim 13 is rejected.
Regarding claim 14, claim 11 is rejected as described above. Claim 14 only provides a functional limitation, not a structural limitation. MPEP 2112.01(II) recites: “"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”. Some members of the sequence space disclosed by claim 11 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 14 is rejected.
Regarding claim 15, claim 14 is rejected as described above. Claim 15 recites further functional limitations but not structural limitations. Some members of the sequence space disclosed by claim 14 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 15 is rejected.
Regarding claim 16, claim 14 is rejected as described above. Claim 16 recites further functional limitations but not structural limitations. Some members of the sequence space disclosed by claim 14 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 16 is rejected.
Regarding claim 18, claim 11 is rejected as described above. Claim 18 only provides a functional limitation, not a structural limitation. MPEP 2112.01(II) recites: “"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.”. Some members of the sequence space disclosed by claim 11 will possess this property, but absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally. Therefore, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Claim 18 is rejected.
Written description support is present for conjugated peptides consisting of SEQ ID NO: 1, 2, or 3 conjugated to nitroxide (3-Carboxy-2,2,5,5-tetramethyl-3-pyrroline-1-yloxy).
New Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 26 is 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 claims contain 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.
Regarding claim 26, claim 26 recites “a conjugated peptide with affinity for or targeted to Akt comprising a peptide conjugated to a nitroxide moiety, wherein the peptide is 5 amino acids in length and comprises the amino acid sequence XaaRXaaRXaa (SEQ ID NO: 4), wherein Xaa is a natural amino acid or a non-natural amino acid, wherein the nitroxide moiety is conjugated to a free N-terminal amine of the peptide, wherein the conjugated peptide inhibits protein oxidation of the targeted Akt protein.”
The peptide length is limited to five amino acids, but this still encompasses 20^3= 8,000 peptides.
In this case, 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 inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (MPEP § 2163 (II.A.3.a.ii.))
According to MPEP § 2163 (II.A.3.a.ii.), a "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Claim 1 encompasses 8,000 peptides and is therefore moderately broad.
MPEP § 2163 (II.A.3.a.ii.) states that “for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus.
In the instant case, Applicant reduces three peptides to practice. At the time the invention was made, the level of skill for preparing and screening polypeptides with desired functional properties was high. However, even if a synthesis and selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify polypeptides with the recited properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by the provided species, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what polypeptide with a particular set of properties would look like structurally.
Applicant discloses SEQ ID NOs: 1, 2, and 3. SEQ ID NO: 1 is five residues and SEQ ID NOs: 2 and 3 are both 13 residues. SEQ ID NO: 1 contains serine residues while SEQ ID NOs: 2 and 3 do not.
The provided examples only represent a limited structural diversity. Since only a limited number of species of peptides are taught within the claimed genus above, the instant claim above fails the written description requirement. A representative number of species has not been taught to describe this genus. Regarding the peptides, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
Given this unpredictability of protein design, the skilled artisan would not have been in possession of the substantial repertoire of peptide species encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genus of every peptide molecule recited by claim 26. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Therefore, claim 26 is rejected.
Regarding claim 27, claim 27 recites a definitive structure and is not subject to this rejection.
Maintained Rejection
Claims 1, 2-6, and 9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for conjugated peptides consisting of SEQ ID NO: 1, 2, or 3 conjugated to nitroxide (3-Carboxy-2,2,5,5-tetramethyl-3-pyrroline-1-yloxy), does not reasonably provide enablement for a peptide of any length or sequence. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
MPEP 2164.01(a) states: “In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is ‘reasonable’ or is ‘undue.’”
These factors include, but are not limited to:
The breadth of the claims;
The claims are extremely broad. Claim 1 encompasses peptides of a vast number of lengths and sequences.
The nature of the invention;
The invention is a conjugated peptide wherein the peptide directs the conjugate to the target Akt and the conjugated antioxidant moiety in inhibits Akt 1 nitration.
The state of the prior art;Rafikov 1 (Rafikov, et al. Journal of Biological Chemistry 288.9: 6212-6226 (2013)) discusses a peptide binding to Akt: “Briefly, the biotinylated peptide substrate
for Akt was incubated with 1 μg of purified Akt1 for 30 min at 30 °C.” (Rafikov 1, page 6213, col. 2, para. 3). Rafikov 1 also discloses the strategy of inhibiting Akt 1 nitration: “Thus, preventing Akt1 nitration may serve as a potential strategy to alleviate deleterious effects of Akt1 activation in various pathologies.” (Rafikov 1, page 6224, col. 1, para. 2) and describes the target: “Furthermore, ADMA
enhanced Akt1 nitration and increased its activity. Mass spectrometry identified a single nitration site in Akt1 located at the tyrosine residue (Tyr350) located within the client-binding domain.” (Rafikov 1, Abstract). Rafikov 2 (Rafikov, et al. Circulation Research 117.suppl_1: A90-A90 (2015)) provides further validation for this concept: “Finally, we have created an anti-oxidant conjugated “shielding” peptide that, by shielding the Akt nitration site, is capable to prevent Akt activation. Indeed, pre-treatment with shielding peptide (100μg/ml, 30min) completely abolished SIN-1 induced nitration of Akt in EC. We conclude that Akt nitration may contribute to proliferative/apoptosis resistant EC phenotype through pathological activation of Akt signaling and Akt mediated mitochondrial eNOS translocation.” (Rafikov 2, Abstract). Comb (US 20020168684, published 11/14/2002) discloses an antibody that can selectively bind to nitrotyrosine motifs: “ The nitrotyrosine polyclonal antibody is highly Specific for nitrated tyrosine, in a manner substantially independent of surrounding amino acid sequence.” (Comb, page 17 para [0174]). Comb goes on to claim such antibodies: “22. The antibody of claim 21, wherein said motif is
selected from the group consisting of a single phosphothreonine, a single phosphoserine, a single phosphotyrosine, a single acetyl-lysine, and a single nitrotyrosine.” and “24. The antibody of claim 23, wherein said kinase Sub
strate motif is selected from the group consisting of a MAPK consensus Substrate motif, a CDK consensus Substrate motif, a PKA consensus substrate motif, an Akt consensus substrate motif, a PKC consensus Substrate motifs, and an ATM
consensus substrate motifs, and wherein said protein binding motif is Selected from the group consisting of a 14-3-3 consensus binding motif, and a PDK1/bulky-ring consensus docking motif.” (Comb, page 59, claims 22 and 24).
Li (Li, Expert Opinion on Therapeutic Patents 17.9: 1077-1130 (2007)) discloses an optimal peptide binding motif to be:
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82
252
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(Li, page 1116, Fig. 8)
The level of one of ordinary skill;
One of ordinary skill in the art is high; typically a master’s level education or higher.
The level of predictability in the art;
The predictability for peptides is low in general due to factors such as effects from point mutations and aggregation as described by Bolognesi et al., Sawai et al, and Wang et al above.
The amount of direction provided by the inventor;
The production and administration of the disclosed peptides are well-known in the art. However, no guidance is provided for sequences significantly larger than 5 or 13 residues.
The existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.Applicant reduces three peptides to practice but claims an enormous sequence space in the independent claims. This would require a tremendous amount of experimentation to find the active peptides from this sequence space.
Regarding claim 1, this claim recites a conjugated peptide of extremely large if not open-ended size. As described above in the Wands analysis, such a large genus would require undue experimentation to make and test. As the peptide length grows is size, additional factors such as aggregation described by Wang become increasingly problematic. This is in addition considerations such as the peptide folding back on itself and blocking the critical residues’ function. Because of the “consisting essentially of” phrase discussed above, this source of rejection is still present in amended claim 1.
Consequently, claim 1 is rejected.
Regarding claims 3-6 and 9, all of these claims recite the open-ended conjugated peptide of claim 1. Consequently, such a large genus would require undue experimentation to make and test. These claims also do not enable the prevention of protein oxidation. Claims 3-6 and 9 are rejected.
Claims 11-16 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for compositions comprising conjugated peptides consisting of SEQ ID NO: 1, 2, or 3 conjugated to nitroxide (3-Carboxy-2,2,5,5-tetramethyl-3-pyrroline-1-yloxy), does not reasonably provide enablement for a composition consisting essentially of a peptide without effective size constraints. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Regarding claim 11, this claim recites a composition with the same scope as claim 1. As described above in the Wands analysis, such a large genus would require undue experimentation to make and test. As the peptide length grows is size, additional factors such as aggregation described by Wang become increasingly problematic. This is in addition considerations such as the peptide folding back on itself and blocking the critical residues’ function. Consequently, claim 11 is rejected.
Regarding claims 12, claim 11 is rejected as described above. Claim 12 introduces some residue identity, but still recites a conjugated peptide of open-ended size. As described above, this requires undue experimentation to make and test. Consequently, claim 12 is rejected.
Regarding claims 13-16 and 18, all of these claims recite the open-ended conjugated peptide of claim 11. Consequently, such a large genus would require undue experimentation to make and test. Claims 13-16 and 18 are rejected.
New Rejection
Claim 26 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for conjugated peptides consisting of SEQ ID NO: 1, 2, or 3 conjugated to nitroxide (3-Carboxy-2,2,5,5-tetramethyl-3-pyrroline-1-yloxy), does not reasonably provide enablement for the 8000 peptides recited by claim 26. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
MPEP 2164.01(a) states: “In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is ‘reasonable’ or is ‘undue.’”
These factors include, but are not limited to:
The breadth of the claims;
The claims are moderately broad. Claim 26 encompasses 8000 peptides as currently claimed.
The nature of the invention;
The invention is a conjugated peptide wherein the peptide directs the conjugate to the target Akt and the conjugated antioxidant moiety in inhibits Akt 1 nitration.
The state of the prior art;Rafikov 1 (Rafikov, et al. Journal of Biological Chemistry 288.9: 6212-6226 (2013)) discusses a peptide binding to Akt: “Briefly, the biotinylated peptide substrate
for Akt was incubated with 1 μg of purified Akt1 for 30 min at 30 °C.” (Rafikov 1, page 6213, col. 2, para. 3). Rafikov 1 also discloses the strategy of inhibiting Akt 1 nitration: “Thus, preventing Akt1 nitration may serve as a potential strategy to alleviate deleterious effects of Akt1 activation in various pathologies.” (Rafikov 1, page 6224, col. 1, para. 2) and describes the target: “Furthermore, ADMA
enhanced Akt1 nitration and increased its activity. Mass spectrometry identified a single nitration site in Akt1 located at the tyrosine residue (Tyr350) located within the client-binding domain.” (Rafikov 1, Abstract). Rafikov 2 (Rafikov, et al. Circulation Research 117.suppl_1: A90-A90 (2015)) provides further validation for this concept: “Finally, we have created an anti-oxidant conjugated “shielding” peptide that, by shielding the Akt nitration site, is capable to prevent Akt activation. Indeed, pre-treatment with shielding peptide (100μg/ml, 30min) completely abolished SIN-1 induced nitration of Akt in EC. We conclude that Akt nitration may contribute to proliferative/apoptosis resistant EC phenotype through pathological activation of Akt signaling and Akt mediated mitochondrial eNOS translocation.” (Rafikov 2, Abstract). Comb (US 20020168684, published 11/14/2002) discloses an antibody that can selectively bind to nitrotyrosine motifs: “ The nitrotyrosine polyclonal antibody is highly Specific for nitrated tyrosine, in a manner substantially independent of surrounding amino acid sequence.” (Comb, page 17 para [0174]). Comb goes on to claim such antibodies: “22. The antibody of claim 21, wherein said motif is
selected from the group consisting of a single phosphothreonine, a single phosphoserine, a single phosphotyrosine, a single acetyl-lysine, and a single nitrotyrosine.” and “24. The antibody of claim 23, wherein said kinase Sub
strate motif is selected from the group consisting of a MAPK consensus Substrate motif, a CDK consensus Substrate motif, a PKA consensus substrate motif, an Akt consensus substrate motif, a PKC consensus Substrate motifs, and an ATM
consensus substrate motifs, and wherein said protein binding motif is Selected from the group consisting of a 14-3-3 consensus binding motif, and a PDK1/bulky-ring consensus docking motif.” (Comb, page 59, claims 22 and 24).
Li (Li, Expert Opinion on Therapeutic Patents 17.9: 1077-1130 (2007)) discloses an optimal peptide binding motif to be:
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(Li, page 1116, Fig. 8)
The level of one of ordinary skill;
One of ordinary skill in the art is high; typically a master’s level education or higher.
The level of predictability in the art;
The predictability for peptides is low in general due to factors such as effects from point mutations and aggregation as described by Bolognesi et al., Sawai et al, and Wang et al above.
The amount of direction provided by the inventor;
The production and administration of the disclosed peptides are well-known in the art.
The existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.Applicant reduces three peptides to practice but claims an enormous sequence space in the independent claims. This would require a large amount of experimentation to find the active peptides from this sequence space.
Regarding claim 26, this claim recites a conjugated peptide with a sequence space of 8000 members. 8000 peptides would require an undue amount of experimentation to synthesize and test for the desired activity. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Consequently, claim 26 is rejected.
Regarding claim 27, this claim recites a definite structure that is fully enabled by the specification.
Response to Arguments
Applicant's arguments filed 3/9/2026 have been fully considered but they are not persuasive.
Applicant asserts: “Claims 1, 3-6, 9, 11-16, and 18 stand rejected under 35 U.S.C. § 112 (a) as allegedly lacking written description. Claims 1, 2-6 and 9 stand rejected under 35 U.S.C. § 112 (a) as allegedly being non-enabled. Additionally, Claims 11-16 and 18 stand rejected under 35 U.S.C. § 112 (a) as allegedly being non-enabled. However, claims 1 and 11 have been amended to specifically recite a "...conjugated peptide...consisting essentially of a peptide according to SEQ ID NO: 1 conjugated to a nitroxide moiety..." Additionally, new Claim 26 now recites a "...conjugated peptide... comprising a peptide conjugated to a nitroxide moiety...the peptide is 5 amino acids in length and comprises the amino acid sequence XaaRXaaRXaa (SEQ ID NO: 4)..."These amendments clarify the identity and length of the peptide, expressly limit the antioxidant moiety to a nitroxide moiety, and further specify the manner in which the nitroxide moiety is attached to the peptide. Taken together, the amendments ensure that the scope of the claims is now fully aligned with the supporting disclosure in the specification. Accordingly, the written description and enablement requirements of § 112(a) are satisfied, and withdrawal of these rejections is respectfully requested..” (Applicant Reply, page 5, para. 4).
Examiner agrees that the removal of “prevent” and “preventing” remedies part of the previous enabled rejection, and this aspect of the enablement rejection has been withdrawn, as shown above.
The term “consisting essentially of”, under broadest reasonable interpretation, still allows for a conjugated peptide has an open-ended number of additional elements that may be added, including additional amino acids.
Regarding new claim 26, new claim 26 is not an open-ended peptide. However, as described above, this still encompasses 8000 amino acids, many of which will likely not function as claimed and are not in the possession of Applicant.
Consequently, rejections are maintained as described above and new rejections directed toward claim 26 are made as described above.
Allowable Subject Matter
Claim 27 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 27 remedies the deficiencies of claim 26 described above by providing a specific and closed peptide sequence. The peptide of SEQ ID NO: 1 is novel and nonobvious rendering the conjugated peptide as a whole novel and nonobvious.
The closest prior art is Li (Li, Expert Opinion on Therapeutic Patents 17.9: 1077-1130 (2007)), which discloses an optimal peptide binding motif to be:
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(Li, page 1116, Fig. 8).
However, the sequence SRIRS does not fit the template disclosed by Li and Li nor any other prior art teaches or suggests a reasonable way to arrive at the sequence of the present application.
Conclusion
No claim is allowed.
Claims 1, 3-6, 9, 11-16, 18, and 26 are rejected.
Claim 27 is objected to.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654