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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/13/2026 has been entered.
Priority
This application was filed on 06/15/2021, which claims the benefit of the priority of US Provisional application PRO 63/038,987 filed 06/15/2020.
Election/Restrictions
Claims 18, 22 and 24 remain withdrawn from further consideration pursuant to 37 CFR
1.142(b) as being drawn to a nonelected Group II and III and/or based on the elected species, there being no allowable generic or linking claim.
Applicant elected with traverse of Group I drawn to methods of enriching collagen fragments, and the dimeric CHP of SEQ ID NO: 2 in the reply filed on 10/15/2024. The requirement is made FINAL in the previous office action.
Claim Status
Claims 1-3, 5-12, 14-19, 21-22, and 24 are pending. Claims 18, 22 and 24 are withdrawn. Claim 1 is amended. Claims 1-3, 5-12, 14-17, 19, and 21 are being examined on the merits in this office action.
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.
Claims 1-3, 5-12, 14-17, 19, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "…removing the collagen fragments from the sample…" in claim 1, part b) line 2. The instant claims do not disclose the specific fragments (i.e. bound or unbound) being removed. The specification from paragraph [0071-0073] discloses situations where the bound or unbound collagen fragments are removed. It is therefore unclear exactly which collagen fragments (i.e. bound or unbound) are being removed from the sample. The new limitations have thus introduced some ambiguity with regards to the type of fragment being removed. Claims 2-3, 5-12, 14-17, 19, and 21 are rejected because they depended on the rejected claim 1.
Claim Interpretation
Enriching collagen fragments – Applicant does not explicitly define “enriching collagen fragments”. However, the instant specification discloses that enriching comprises “combining a sample comprising collagen fragments with a composition comprising any one of the dimeric CHPs, and wherein the first CHP and second CHP bind to and form a triple helix with a collagen fragment; removing all unbound collagen fragments or other unbound components from the sample, and optionally analyzing the triple helix”. Instant specification discloses that enrichment is for accurate detection and analysis [0004].
Collagen fragments – Examiner notes that the instant invention defines collagen fragments as “denatured collagen”. See [0004, 0006, 0075]. Thus, prior art references that teach denatured collagen would read on the instant “collagen fragments”.
Further, in view of the disclosure in paragraph [0041, 0044], Examiner in interpreting the Glycine in claim 1 to include both glycine and its modified form. The “a glycine” recited in claim 9 is interpreted to mean “at least one glycine”.
Claim Rejections - 35 USC § 102 - Maintained
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-12, 14-17, 19, and 21 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kessler et al. (US20180000960A1 – hereinafter “Kessler”).
Regarding claim 1, Kessler teaches a method that comprises contacting denatured collagen in a sample comprising peptide conjugate and detecting the binding of the peptide conjugate to the denatured collagen, that the presence of binding indicating the presence of denatured collagen in the sample (Abstract; claims 30, 61), that the peptide conjugate comprises a dimeric collagen hybridizing peptide comprising a first and second collagen hybridizing peptide; a linker; and a branch point, wherein the first and second collagen hybridizing peptides comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12 (claim 1; [0014-0015]) and they bind to form a triple helix [0105, 0109, 0110, 0116], that the bound collagen fragments are removed from CHP [0117, 0120]. Examiner notes that this teaching reads on the instant “..releasing the bound fragments”. Kessler further teaches removal of unbound or non-triple helix peptide [0034]. Examiner notes that this teaching reads on the instant “..removing the collagen fragments..”. Kessler teaches that the presence of binding can be determined using an immunoassay, a fluorescence assay or an enzyme-based assay [0085-0088]. The disclosure of Kessler anticipates claim 1.
Regarding claim 2, Kessler teaches that CHP is attached or conjugated to a solid support [0059].
Regarding claim 3, Kessler teaches that CHP is attached or conjugated to a solid support, that the solid support can be attached via an attachment point present between the branch point and the solid support, that the branch point also serves as the attachment point for the solid support, wherein the solid supports can be, but are not limited to, resin, polymeric beads, agarose beads [0059].
Regarding claim 5-6, Kessler teaches that wherein the first and second collagen hybridizing peptides are identical (claim 2; [0137]) or wherein the first and second collagen hybridizing peptides are different (claim 3).
Regarding claim 7, Kessler teaches that wherein X is proline, modified proline, glutamic acid, or aspartic acid (claim 4; [0054]).
Regarding claim 8, Kessler teaches that wherein Y is a modified proline, lysine, or arginine (claim 5; [0054]).
Regarding claim 9, Kessler teaches that wherein a glycine is modified as an Aza-glycine (claim 7; [0007, 0055]).
Regarding claims 10-12, Kessler teaches that wherein the linker is between the collagen hybridizing peptides and the branch point (claim 8), that wherein there are at least two linkers (claim 9), wherein the linker and branch point are on the C-terminal end of the first and second collagen hybridizing peptides (claim 10) and wherein the linker and branch point are on the N-terminal end of the first and second collagen hybridizing peptides (claim 11).
Regarding claim 14, Kessler teaches that wherein the linker is one or more glycine residues, aminohexanoic acid, or polyethylene glycol (PEG) (claim 12).
Regarding claim 15, Kessler teaches that wherein the branch point attaches to a linker which is attached to the first collagen hybridizing peptide and to a linker which is attached to second collagen hybridizing peptide (claim 14).
Regarding claim 16, Kessler teaches that wherein the branch point is a lysine residue (claim 15; [0057, 0106]).
Regarding claim 17, Kessler teaches that wherein the dimeric peptide comprises the formula
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(claim 17; [0010]).
Regarding claim 19, Kessler teaches that the presence of binding can be determined using an immunoassay, a fluorescence assay or an enzyme-based assay [0085-0088].
Claim Rejections - 35 USC § 103 - Maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 21 remains rejected under 35 U.S.C. 103 as being unpatentable over Kessler et al. (US20180000960A1 – hereinafter “Kessler”, cited and enclosed in the previous office action) as applied to claim 1 above, and further in view of Takita et al. (ChemBioChem. 2018, 19, 1613 – 1617).
The teachings of Kessler are disclosed above and incorporated herein by reference.
Additional teachings by Kessler are disclosed below.
Kessler teaches that collagen hybridizing peptides (CHPs, molecular weight 2-3 kDa), are also known as collagen mimetic peptides (CMP) [0103].
Kessler does not teach that the dimeric CHP is cyclic as recited in claim 21.
Takita et al. teaches a new class of collagen-binding peptides, cyclic collagen-mimetic peptides (cCMPs), that efficiently hybridize with the triple-helix-forming portions of collagen. Examiner herein notes that it is known in the art that collagen-mimetic peptides (CMP’s) and collagen hybridizing peptides (CHP’s) are used interchangeably as taught by Kessler. Takita teaches that cCMPs are composed of two parallel collagen-like (Xaa-Yaa-Gly)n strands with both termini tethered by covalent linkages (Abstract). Takita teaches that molecular-dynamics simulations suggested that a cCMP forms a more stably hybridized product than its single-chain counterpart; this could explain why cCMP has higher affinity toward denatured collagen (Abstract; Fig. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Kessler and use a cyclic dimeric CHP as taught by Takita since Takita teaches that the cyclic CHP efficiently hybridized with the triple-helix-forming portions of collagen (Abstract). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the cyclic CHP of Takita since Takita teaches that they form a more stably hybridized product than its single-chain counterpart, and that this could explain why cCMP has higher affinity toward denatured collagen (Abstract; Fig. 2). The disclosures render obvious claim 21.
Response to Arguments
Applicant's arguments filed 07/13/2026 have been fully considered but they are not persuasive.
Applicant arguments
Applicant argues that Kessler describes breaking the triple helix, the collagen is, at best, released from the dCHP but the collagen remains in the sample with the dCHP. This is evidenced by para [0119] of Kessler further teaching that the collagen and the dCHP eventually refold into the triple helix again upon adjusting the temperature (Page 6-7 of Arguments).
Applicant argues that Takita fails to teach or suggest a "releasing the bound collagen fragments from the dimeric CHP and removing the collagen fragments from the sample (Page 8 of Arguments).
Examiner’s Response
The arguments disclosed above have been fully considered but are unpersuasive. Examiner notes that Kessler teaches a method that comprises contacting denatured collagen in a sample comprising peptide conjugate and detecting the binding of the peptide conjugate to the denatured collagen, that the presence of binding indicating the presence of denatured collagen in the sample (Abstract; claims 30, 61), that the peptide conjugate comprises a dimeric collagen hybridizing peptide comprising a first and second collagen hybridizing peptide; a linker; and a branch point, wherein the first and second collagen hybridizing peptides comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12 (claim 1; [0014-0015]) and they bind to form a triple helix [0105, 0109, 0110, 0116], that the bound collagen fragments are removed from CHP [0117, 0120]. Examiner notes that Kessler teaches both binding dimeric CHP to gelatin and collagen fragments. Kessler teaches that the bound collagen fragments are removed from CHP [0117, 0120]. Examiner notes that this teaching reads on the instant “..releasing the bound fragments”. Kessler further teaches removal of unbound or non-triple helix peptide [0034]. Examiner notes that this teaching reads on the instant “..removing the collagen fragments..”. The arguments are unpersuasive.
Claim Rejections - 35 USC § 102 - New
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5, 7-8, 10-12, 14-17 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kessler et al. (J. Proteome Res. 2020, 19, 2926−2932 – hereinafter “Kessler”).
Kesler teaches enrichment of collagen fragments comprising combining dimeric CHP (D-CHP) with urine from a mouse model of postmenopausal osteoporosis, in which bilateral ovariectomy (OVX) leads to estrogen depletion, bone loss, and high collagen degradation activity, that the D-CHP was solid supported with avidin beads and the beads were then washed extensively to remove nonspecifically adsorbed materials, followed by releases the bound collagen fragments (Page 2929, right col., 1st and 2nd paragraphs). Kessler teaches that the D-CHP with sequence [Ac-(GPO)6-G3]2-K-GK, designated as D-CHP, was designed to hybridize to collagen fragments via 1:1 stoichiometry. The peptide was synthesized by incorporating a parallel protected Fmoc-Lys(Fmoc)-OH residue during the Fmoc-mediated solid phase peptide synthesis (SPPS), and the two GPO chains were extended simultaneously after the branch point and that it has the ability to form a triple helix (Page 2928, right col., 2nd paragraph, line 1-9; Fig. 1-2). Examiner notes that the D-CHP of Kesler reads the instant D-CHP wherein the dimeric CHP comprises a first CHP and a second CHP, one or more linkers, and a branch point, wherein the first CHP and second CHP comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12, and wherein the first CHP and second CHP bind to and form a triple helix with a collagen fragment. The disclosure anticipate claim 1.
Regarding claim 2, Kessler teaches that D-CHP is conjugated to a support (Page 2929, right col., line 5-10).
Regarding claim 3, Kessler teaches that the support is avidin beads (Page 2929, right col., whole of 1st and 2nd paragraph).
Regarding claim 5, Kessler teaches that the D-CHP has the sequence [Ac-(GPO)6-G3]2-K-GK (Page 2928, right col., 2nd paragraph, line 1-9; Fig. 1-2), which discloses that the first and second CHP are identical.
Regarding claims 7-8, Kessler teaches that the D-CHP has the sequence [Ac-(GPO)6-G3]2-K-GK (Page 2928, right col., 2nd paragraph, line 1-9; Fig. 1-2), which shows that X is proline and Y is hydroxyproline which reads on modified proline.
Regarding claim 10-12, Kessler teaches that the D-CHP has the sequence [Ac-(GPO)6-G3]2-K-GK (Page 2928, right col., 2nd paragraph, line 1-9; Fig. 1-2), which shows that the linker G3 is between the CHP and the branch point, K. The disclosures of Kessler also indicate that the D-CHP contains two linkers. Additionally, the D-CHP disclosed in Fig. 2-3, shows that the linker and branch point are on the C or N-terminal end of the first and second CHP.
Regarding claim 14-17, Kessler teaches that the D-CHP has the sequence [Ac-(GPO)6-G3]2-K-GK (Page 2928, right col., 2nd paragraph, line 1-9; Fig. 1-2), which shows that the linker G3 is one or more glycine residues and further shows that the branch point attaches to a linker which is attached to the first CHP and to a linker which is attached to second CHP and also shows that the branch point is a lysine residue. Examiner further notes that the D-CHP of Kessler comprises the instant SEQ ID NO: 2.
Regarding claim 19, Kessler teaches peptidomic analysis of collagen fragments (Abstract; Page 2927, left col., 2nd paragraph, line 9-12).
Double Patenting - Maintained
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, 5-12, 14-17 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 18 of U.S. Patent No. US10953104B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent recite a peptide conjugate comprising a) an active agent; b) a spacer moiety; and c) a dimeric collagen hybridizing peptide comprising i) a first and second collagen hybridizing peptide;
ii) a linker; and iii) a branch point, wherein the first and second collagen hybridizing peptides comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12, and wherein the first and second collagen hybridizing peptides are capable of forming a triple helix with collagen (claim 1). The claims of the patent further teach a method of detecting denatured collagen in a sample comprising a) contacting a composition comprising the peptide conjugate of claim 1 to a sample, wherein the active agent comprises a therapeutic agent, b) detecting the presence or absence of binding of the peptide conjugate to denatured collagen, the presence of binding indicating the presence of denatured collagen in the sample (claim 18). Examiner notes that the claims of the patent anticipate instant claim 1.
The claims of the patent further recite The peptide conjugate of claim 1, wherein the first and second collagen hybridizing peptides are identical (claim 2), wherein the first and second collagen hybridizing peptides are different (claim 3), wherein X is proline, modified proline, glutamic acid, or aspartic acid (claim 4), wherein Y is a modified proline, lysine, or arginine (claim 5), wherein a glycine is modified as an Aza-glycine (claim 6), wherein the linker is between the collagen hybridizing peptides and the branch point (claim 7), wherein there are at least two linkers (claim 8), wherein the linker and branch point are on the C-terminal end of the first and second collagen hybridizing peptides (claim 9), wherein the linker and branch point are on the N-terminal end of the first and second collagen hybridizing peptides (claim 10). Examiner notes that these claims are identical to the instant claims 5-12.
The claims of the patent further recite that wherein the linker is one or more glycine residues, aminohexanoic acid, or polyethylene glycol (PEG) (claim 11), wherein the branch point attaches to a linker which is attached to the first collagen hybridizing peptide and to a linker which is attached to second collagen hybridizing peptide (claim 12), wherein the branch point is a lysine residue (claim 13), wherein the dimeric peptide comprises the formula
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(claim 14). Examiner notes that these claims are identical to the instant claims 14-17.
Response to Arguments
Applicant's argument has been fully considered but is not found persuasive because only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. MPEP §804. Therefore, the nonstatutory double patenting rejections are maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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