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 .
DETAILED ACTION
Response to Election/Restriction filed on June 17, 2026 is acknowledged. Claims 1-7, 9, 12-13, 15-20, 22, 23, 25-26 are pending in the instant application.
Election/Restrictions
Applicant initially elected without traverse Group I, drawn to an isolated ApoC-II mimetic and without traverse SEQ ID NO:34 as the peptide, R8 and R5 as the linkage ((hydrocarbon staple) and N-terminal acetylation (claims 5-6) in the reply filed June 17, 2026.
The restriction is deemed proper and is made FINAL in this office action. Claims 7, 17-20, 22-23, 25-26 are withdrawn from consideration as being drawn to non-elected invention/species.
Claims 1-6, 9, 12-13 and 15-16 are examined on the merits of this office action.
Claim Objection
Claim 9 is objected to for the following minor informality: the “:” should be removed after peptide in the first line.
Claim Rejections - 35 USC § 112, First Paragraph
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 1-6, 9, 12-13 and 15-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that 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, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the Claims
Claim 1 broadly recites an isolated ApoC-II mimetic peptide comprising only a limited number of structural characteristics including a peptide of 19–35 amino acids; one or two helical domains; one or more covalent linkages joining at least two non-contiguous amino acids; and at least one amphipathic helical domain. Claim 1 contains no amino acid sequence limitations, no sequence identity limitations, no residue conservation requirements, no defined location of the helical domains or covalent linkage(s), and no structural features that distinguish the claimed peptides from other peptides possessing the recited structural characteristics. Accordingly, claim 1 encompasses a vast genus of peptides. Further, the recitation of an “ApoC-II mimetic peptide” is not merely a structural designation. As described in paragraph [0067], the specification characterizes ApoC-II mimetic peptides by their biological activities, including increasing lipoprotein lipase (LPL) activity, decreasing ApoC-III binding to VLDL, reducing serum triglycerides, reducing serum cholesterol, or combinations thereof. Claim 13 further claims wherein the peptide activates lipoprotein lipase and/or wherein the peptide displaces ApoC-III from vLDL. Thus, the claim encompasses peptides that perform the functional properties associated with ApoC-II mimicry without reciting structural features that define that functional class.
Actual Reduction to Practice
The specification demonstrates actual reduction to practice only for specific peptide embodiments. The disclosure provides representative peptide sequences identified as SEQ ID NOS: 1–43 and experimental data evaluating selected peptides for LPL activation, ApoC-III displacement, triglyceride reduction, cholesterol reduction, proteolytic stability, and related properties. These examples establish possession of those specific peptide species and closely related embodiments, but do not demonstrate possession of the entire genus encompassed by claim 1.
Sufficient Relevant Identifying Characteristics
The specification does not provide sufficient identifying structural characteristics that would permit one of ordinary skill in the art to recognize the full genus of claimed ApoC-II mimetic peptides. Instead, the disclosure primarily identifies specific peptide sequences and selected modifications. Although the specification describes exemplary hydrocarbon staples, stitches, lactam bridges, disulfide bonds, and certain modified residues, it does not disclose common structural features that distinguish all peptides within the claimed genus from peptides outside the genus. The claim therefore relies primarily upon the designation “ApoC-II mimetic” rather than objective structural characteristics defining the full scope of the claimed peptides.
Physical and Chemical Properties
The specification describes physical and chemical characteristics only for selected peptide embodiments, including particular stapled, stitched, lactam-bridged, acetylated, fatty-acid modified, and FcRn-linked peptides. However, the disclosure does not identify physical or chemical properties common to the entire breadth of peptides encompassed by claim 1 that would permit one of ordinary skill in the art to recognize all members of the claimed genus.
Functional Characteristics Coupled with a Known or Disclosed Correlation Between Structure and Function
Although paragraph [0067] attributes biological functions to ApoC-II mimetic peptides, including increased LPL activity, decreased ApoC-III binding, reduced triglycerides, and reduced cholesterol, the specification does not disclose a sufficient correlation between the limited structural features recited in claim 1 and these functional characteristics across the full breadth of the claimed genus. The disclosure demonstrates functional activity only for specific peptide sequences and variants tested in the Examples. The specification does not identify structural rules or conserved sequence features that would allow one of ordinary skill in the art to conclude that substantially all peptides encompassed by claim 1 would possess the functional characteristics associated with ApoC-II mimicry. Consequently, the functional designation “ApoC-II mimetic” is not adequately supported across the full scope of claim 1.
Method of Making
Although the specification describes methods for preparing the disclosed peptide embodiments, including chemical synthesis and incorporation of particular hydrocarbon staples, stitches, lactam bridges, and other modifications, the ability to make peptides does not demonstrate possession of the entire claimed genus. The written description requirement is satisfied by demonstrating possession of the claimed invention, not merely by describing methods capable of producing peptide variants.
Conclusion
Accordingly, the specification does not reasonably convey to one of ordinary skill in the art that Applicant had possession of the full scope of the genus recited in claim 1 at the time of filing. The disclosure establishes possession of specific disclosed peptide species and certain closely related variants, but does not provide sufficient representative species, common structural features, or a demonstrated correlation between the limited structural limitations recited in claim 1 and the functional characteristics required by the designation “ApoC-II mimetic peptide.” Therefore, claims 1-6, 9, 12-13, 15-16 fail to comply with the written description requirement of **35 U.S.C. § 112(a).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “one or more covalent linkages”, thereby introducing one or more linkage elements. However, claim 2 subsequently refers to “the covalent linkage” in the singular. It is unclear whether claim 2 is intended to refer to one of the recited covalent linkages, each of the recited covalent linkages, or all of the recited covalent linkages. Accordingly, the metes and bounds of claim 2 are not reasonably certain. A suggested amendment to overcome this rejection would be to refer to the “one or more covalent linkages” or “wherein each of the one or more covalent linkages”.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-6, 12-13, 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Remaley (US20200140522 A1) in view of Remaley* (WO2012149563 A1) *Both references cited in Applicant’s IDS.
Remaley teaches ApoC-II mimetic peptides useful for treating hypertriglyceridemia and related lipid disorders by increasing lipoprotein lipase activity and lower serum triglycerides ( see abstract). Remaley teaches ApoC-II mimetic peptides comprising amphipathic alpha helical domains, including peptides having lengths overlapping with the presently claimed 19-35 amino acids, as well as numerous variants including substitutions, deletions, truncations, D amino acid substitutions, modified amino acids, fatty acid conjugation, N-terminal acylation and acetylation (see paragraph 0254, 0186), C terminal amidation and pharmaceutical formulations (paragraph 0032) thereof (for example SEQ ID Nos:34-55, including SEQ ID NO:49 and modified derivatives of SEQ ID Nos:50-52). SEQ ID Nos:49-50 are 21mer ApoC-II mimetic peptide comprising a helical domain. Remaley teaches SEQ ID NO:49 which corresponds to the same ApoC-II mimetic peptide backbone of the instant application (instant SEQ ID NO:7). Remaley teaches that the ApoC-II mimetic peptides may be chemically modified using known peptide modification techniques including hydrocarbon stapling (to stabilize alpha helix conformation), lactam formation, acylation, alkylation and covalent attachment of non-protein polymers to improve peptide properties (see paragraphs 0104, 187, 204 and 230).
However, although Remaley primarily recognizes hydrocarbon stapling for stabilization, it does not teach an ApoC-II mimetic peptide containing a hydrocarbon staple formed by replacing amino acid residues with hydrocarbon stapling amino acids, such as (S)-alpha-methyl-alpha-pentenylglycine (S5), R5, S8 or R8 followed by closing to form a covalent linkage joining non-contiguous amino acid residues.
However, Remaley* teaches hydrocarbon stapling of amphipathic apolipoprotein mimetic peptides by replacing selected amino acid residues with hydrocarbon stapling amino acids including S5, R4, S8 and R8, followed by ring closure to form a hydrocarbon staple joining noncontiguous amino acid residues (see paragraphs 113-115 and 129). Remaley* further teaches positioning the hydrocarbon staple on the hydrophobic face of the amphipathic alpha helix to stabilize helical confirmation (see paragraph 0114). Remaley* demonstrates that hydrocarbon stapling improves alpha helicity, proteolytic stability, cholesterol efflux activity, and in vivo efficacy of apolipoprotein mimetic peptides (see abstract, paragraph 0007, see paragraph 0021 for example, paragraph 0029, paragraph 0120-0122).
It would have been obvious before the effective filing date of the claimed invention to modify the Apo-C II mimetic peptides of Remaley using the specific hydrocarbon stapling chemistry taught by Remaley*. One of ordinary skill in the art would have been motivated to do so because Remaley itself recognizes hydrocarbon stapling as a desirable modification of stabilization of the alpha helix while Remaley* teaches precisely how to implement that modification in structurally similar apolipoprotein mimetic peptides and demonstrates that such modification stabilizes the alpha helix, increases helicity, improves proteolytic resistance, and enhances biological activity. Since both references concern amphipathic apolipoprotein mimetic peptides for treatment of lipid disorders, one of ordinary skill in the art would have had a reasonable expectation that applying the known hydrocarbon stapling techniques of Remaley* to the ApoC-II mimetic peptides of Remaley would provide the same predictable benefits.
Furthermore, claims 2–6 are met by the combined references because the Remaley* teaches hydrocarbon staples comprising covalent linkages joining non-contiguous amino acid residues positioned on the hydrophobic face of an amphipathic α-helix (paragraph 114), hydrocarbon staples, and the use of S5, R5, S8, and R8 stapling amino acids (paragraphs 113–115, 129). As stated above, Remaley teaches ApoC-II mimetic peptides comprising further modifications including fatty acid conjugation, N-terminal acylation and acetylation (see paragraph 0254, 0186), C terminal amidation and pharmaceutical formulations (paragraph 0032) thereof (for example SEQ ID Nos:34-55, including SEQ ID NO:49 and modified derivatives of SEQ ID Nos:50-52).
Claims 12–13 are met because the Remaley teaches ApoC-II mimetic peptides having lengths overlapping the claimed 19–25 amino acids and teaches activation of lipoprotein lipase (see paragraph 0031), displacement of ApoC-III (paragraph 0031), and reduction of serum triglycerides (see abstract, also SEQ ID Nos:49-52). Claims 15–16 are met because the Remaley teaches pharmaceutical compositions comprising ApoC-II mimetic peptides together with pharmaceutically acceptable carriers and teaches intravenous, subcutaneous, and oral administration (paragraphs 0032-0033, 0124).
Furthermore, the staple modification merely applies a known peptide stabilization technique to a known peptide to obtain the predictable improvements expressly taught in the prior art. Such modification constitutes the application of a known technique to improve a similar composition in the same manner and the substitution of one known element for another to obtain predictable results. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007); MPEP §§2143(I)(B) and 2143(I)(C).
Claim(s) 9 is rejected under 35 U.S.C. 103 as being unpatentable over Remaley (US20200140522 A1) in view of Remaley* (WO2012149563 A1) as applied to Claim(s) 1-6, 12-13, 15-16 above, in further view of Ali (Computational and Structural Biotechnology Journal 17 (2019) 263–281).
As discussed above, the combined teachings of the Remaley and Remaley* renders obvious an ApoC-II mimetic peptide comprising a hydrocarbon staple. Remaley further teaches SEQ ID NOs. 49-52, which corresponds to the peptide backbone of instant SEQ ID NO. 7, differing only by incorporation of hydrocarbon stapling residues at the corresponding positions to generate a hydrocarbon-stapled peptide. Thus, Remaley teaches the same ApoC-II mimetic peptide scaffold modified through hydrocarbon stapling. Although the combined references do not expressly disclose the exact peptide designated as instant SEQ ID NO. 7, claim 9 is not limited to that exact sequence. Rather, claim 9 encompasses peptides having at least 90% sequence identity to the recited sequences. Remaley teaches numerous closely related ApoC-II mimetic peptide variants and chemically modified derivatives while maintaining ApoC-II mimetic activity, thereby demonstrating that limited sequence variation within the peptide family was well known.
Ali teaches that hydrocarbon stapling of α-helical peptides was a well-established design strategy and explains that hydrocarbon staples are routinely introduced at conventional α-helical spacings, particularly i,i+4 and i,i+7, using α-methyl-α-pentenylglycine and α-methyl-α-octenylglycine residues (see page 539, left column, “hydrocarbon stapling”). Ali further teaches that staple placement is selected through routine optimization to stabilize α-helical conformation while preserving peptide function (page 539, left column, last full paragraph continuing into the right column). Figure 1 of Ali further illustrates representative hydrocarbon stapling geometries positioned at i,i+4 and i,i+7 within alpha-helical peptides.
Accordingly, it would have been obvious to one of ordinary skill in the art to incorporate the hydrocarbon stapling chemistry taught by the Remaley* into the known ApoC-II mimetic peptides of the Remaley at conventional α-helical staple positions as taught by the Ali, with a reasonable expectation of success in obtaining stabilized ApoC-II mimetic peptides exhibiting improved helicity, conformational stability, proteolytic resistance, and biological activity. Because claim 9 encompasses peptides having at least 90% sequence identity, routine optimization of staple placement and minor sequence variation while preserving the known ApoC-II mimetic scaffold would have predictably yielded peptides falling within the scope of the claim. Such routine optimization of known variables to obtain predictable results would have been within the ordinary skill in the art. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) and MPEP §§2143(I)(B), 2143(I)(C), and 2144.05.
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 1-6, 9, 12-13, 15-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11136372 in view of Remaley, Remaley and Ali (see above cited references). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims an ApoC-II mimetic of 19-35 amino acids in length (claim 1); covalent linkage between two noncontiguous amino acids (claim 1); between two amino acids on the hydrophobic side of the helical domain (Claim 2); hydrocarbon staple (claim 3), ; S5, R5, B5 or R8 linkage (claim 4); further modifications (Claims 5-6); SEQ ID NO:7 (Claim 9); pharmaceutical formulations and routes of administration (Claims 15-16).
US Patent No. ‘372 claims “ An isolated apoC-II mimetic peptide of no more than 50 amino acids, comprising from N-terminus to C-terminus a first helical domain, a hinge region, and a second helical domain, wherein the first helical domain is amphipathic, and wherein the apoC-II mimetic peptide is not a peptide of SEQ ID NO: 56, wherein the hinge region comprises a valine” (claim 1) and pharmaceutical formulations (claims 6-7, main utility of the peptide) and suitable for subcutaneous injection (claim 7)..
US Patent No. ‘372 is silent to one or more covalent linkages joining at least two non-contiguous amino acids; hydrocarbon staple; S5, R5, B5 or R8 linkage; further modifications; SEQ ID NO:7.
However, Remaley teaches ApoC-II mimetic peptides useful for treating hypertriglyceridemia and related lipid disorders by increasing lipoprotein lipase activity and lower serum triglycerides ( see abstract). Remaley teaches ApoC-II mimetic peptides comprising amphipathic alpha helical domains, including peptides having lengths overlapping with the presently claimed 19-35 amino acids, as well as numerous variants including substitutions, deletions, truncations, D amino acid substitutions, modified amino acids, fatty acid conjugation, N-terminal acylation and acetylation (see paragraph 0254, 0186), C terminal amidation and pharmaceutical formulations (paragraph 0032) thereof (for example SEQ ID Nos:34-55, including SEQ ID NO:49 and modified derivatives of SEQ ID Nos:50-52). SEQ ID Nos:49-50 are 21mer ApoC-II mimetic peptide comprising a helical domain. Remaley teaches SEQ ID NO:49 which corresponds to the same ApoC-II mimetic peptide backbone of the instant application (instant SEQ ID NO:7). Remaley teaches that the ApoC-II mimetic peptides may be chemically modified using known peptide modification techniques including hydrocarbon stapling (to stabilize alpha helix conformation), lactam formation, acylation, alkylation and covalent attachment of non-protein polymers to improve peptide properties (see paragraphs 0104, 187, 204 and 230).
Remaley* teaches hydrocarbon stapling of amphipathic apolipoprotein mimetic peptides by replacing selected amino acid residues with hydrocarbon stapling amino acids including S5, R4, S8 and R8, followed by ring closure to form a hydrocarbon staple joining noncontiguous amino acid residues (see paragraphs 113-115 and 129). Remaley* further teaches positioning the hydrocarbon staple on the hydrophobic face of the amphipathic alpha helix to stabilize helical confirmation (see paragraph 0114). Remaley* demonstrates that hydrocarbon stapling improves alpha helicity, proteolytic stability, cholesterol efflux activity, and in vivo efficacy of apolipoprotein mimetic peptides (see abstract, paragraph 0007, see paragraph 0021 for example, paragraph 0029, paragraph 0120-0122).
It would have been obvious before the effective filing date of the claimed invention to use the 19-35mer ApoC II mimetic peptides of Remaley as the mimetic peptides of US Patent No. ‘372 and to use the specific hydrocarbon stapling chemistry taught by Remaley*. One of ordinary skill in the art would have been motivated to do so because the ApoC-II peptides of Remaley would fall within the scope of claim 1 and would have the desired functional properties/purpose of US Patent No. ‘372 and teaches that hydrocarbon stapling as a desirable modification of stabilization of the alpha helix. Furthermore, Remaley* teaches precisely how to implement that modification in structurally similar apolipoprotein mimetic peptides and demonstrates that such modification stabilizes the alpha helix, increases helicity, improves proteolytic resistance, and enhances biological activity.
Regarding claim 9, the combined teachings of the US Patent NO. ‘372 in view of Remaley and Remaley* renders obvious an ApoC-II mimetic peptide comprising a hydrocarbon staple.
Remaley further teaches SEQ ID NOs. 49-52, which corresponds to the peptide backbone of instant SEQ ID NO. 7, differing only by incorporation of hydrocarbon stapling residues at the corresponding positions to generate a hydrocarbon-stapled peptide. Thus, Remaley teaches the same ApoC-II mimetic peptide scaffold modified through hydrocarbon stapling. Although the combined references do not expressly disclose the exact peptide designated as instant SEQ ID NO. 7, claim 9 is not limited to that exact sequence. Rather, claim 9 encompasses peptides having at least 90% sequence identity to the recited sequences. Remaley teaches numerous closely related ApoC-II mimetic peptide variants and chemically modified derivatives while maintaining ApoC-II mimetic activity, thereby demonstrating that limited sequence variation within the peptide family was well known.
Ali teaches that hydrocarbon stapling of α-helical peptides was a well-established design strategy and explains that hydrocarbon staples are routinely introduced at conventional α-helical spacings, particularly i,i+4 and i,i+7, using α-methyl-α-pentenylglycine and α-methyl-α-octenylglycine residues (see page 539, left column, “hydrocarbon stapling”). Ali further teaches that staple placement is selected through routine optimization to stabilize α-helical conformation while preserving peptide function (page 539, left column, last full paragraph continuing into the right column). Figure 1 of Ali further illustrates representative hydrocarbon stapling geometries positioned at i,i+4 and i,i+7 within alpha-helical peptides.
Accordingly, it would have been obvious to one of ordinary skill in the art to incorporate the hydrocarbon stapling chemistry taught by the Remaley* into the ApoC-II mimetic peptides conventional α-helical staple positions as taught by the Ali, with a reasonable expectation of success in obtaining stabilized ApoC-II mimetic peptides exhibiting improved helicity, conformational stability, proteolytic resistance, and biological activity.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
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