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 .
Claim Status
Claims 1, 3-5, 7-14, 16-19, 24, 28, 30, 36, and 42-43 are pending.
Claims 1, 3-5, 7-14 , and 24 are currently amended and claims 42-43 are new.
Claims 2, 6, 15, 20-23, 25-27, 29, 31-35, and 37-41 are cancelled.
Claims 28, 30, and 36 are withdrawn as being directed to a non-elected method invention and claims 16-19 are further withdrawn as being directed to a non-elected species.
Claims 1, 3-5, 7-14, 24, and 42-43 have been examined.
Priority
This application is a 371 of PCT/US2022/012253 01/13/2022
PCT/US2022/012253 has PRO 63/137,354 01/14/2021
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/17/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Withdrawn Objection
The objection of claim 10, 12, and 14 is withdrawn because the amendments to the claims overcome the rejection.
Maintained Rejection
Claim Rejections - 35 USC § 103
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.
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.
1. Claims 1, 3-5, 7-11, 14, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Cummings et al. (US 2016/0108092 A1) in view of Veronese (Biomaterials 22 (2001) 405-417).
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Claim 1 is drawn to a conjugate of PEG-(L1)-Y1X1Y2X2X3Y3 X4X5X6Z1 X7W1 (SEQ ID NO: 1) or its pharmaceutically acceptable sale thereof, wherein:
Cummings et al. teach selectin inhibitors, compositions, and methods of using the compositions (Abstract). Cummings et al. teach the selectin inhibitor formula of SEQ ID NO: 1 (Y1X1Y2X2X3Y3 X4X5X6Z1 X7W1) [0009, claim 1] and definition of each variables [0011-0013]. Cummings et al. show the peptide sequences of SEQ ID NO; 2-12 [0082, claim 12] including the elected glycopeptide peptide species of SEQ ID NO: 12 [0083-0086].
Veronese teaches peptide and protein PEGylation (Title). Veronese teaches advantages of PEG conjugation comprising increase of the molecular size of the polypeptide to reduce its renal ultrafiltration, reducing the degradation by proteolytic enzymes and modifying biodistribution and solubility of the PEGylated peptide (p406, col 1, para1). Veronese teaches amino groups,
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namely the alpha amino or the epsilon amino of lysine, are the usual sites of PEG linking (p407, col 1, para 1). Veronese shows PEGylation of peptide can be formed by Alkylating PEGs(p407, Fig 2) or Acylating PEGs shown as follows (p407, Fig 3).
Because Veronese teaches advantages of PEG conjugation comprising increase of the molecular size for a small polypeptide to reduce its renal ultrafiltration, reducing the degradation by proteolytic enzymes and modifying biodistribution and solubility of the PEGylated peptide (p406, col 1, para1), one of ordinary skill in the art would have found it obvious to beneficial conjugate PEG to Cummings’s small glycopeptide to reduce renal ultrafiltration of Cummings’s small glycopeptide, reduce its degradation by proteolytic enzymes and modifying biodistribution and solubility of the PEGylated small glycopeptide.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Cummings’s glycopeptide with Veronese’s PEG because (a) Cummings’s glycopeptides SEQ ID Nos: 1-12 are short and small peptide and (b) Veronese teaches benefits of PEGylation comprising (i) increase of the molecular size for a small polypeptide to reduce its renal ultrafiltration, (ii) reducing the degradation by proteolytic enzymes and (iii) modifying biodistribution and solubility of the PEGylated peptide (p406, col 1, para1). The combination would have reasonable expectation of success because Veronese shows PEGylation of peptide can be formed by Alkylating PEGs (p407, Fig 2) or Acylating PEGs (p407, Fig 3).
With respect to claims 1, 3-5, and 9, Cummings et al. teach the selectin inhibitor formula of SEQ ID NO: 1 (Y1X1Y2X2X3Y3 X4X5X6Z1 X7W1) [0009, claim 1] with defined variables [0011-0013]. Cummings et al. further show the elected glycopeptide peptide species of SEQ ID NO: 12 (KEY1EY2LDY3DFLZ1EW1EPL) or salt thereof [0083-0086].
With respect to claim 7, Cummings et al. teach saccharide structure as follows.
2-(acetylamino)-2-deoxy-galactose alpha 1 bonded to W1 [0073]
a first galactose beta 3 bonded to 2-(acetylamino)-2-deoxy-galactose [0074]
2-(acetylamino)-2-deoxy-glucose beta 6 bonded to 2-(acetylamino)-2-deoxy-galactose [0075]
fucose alpha 3 bonded to 2-(acetylamino)-2-deoxyglucose [0078]
a second galactose beta 4 bonded to 2-(acetylamino)-2-deoxy-glucose [0076], and
5-acetamido-3,5-dideoxy-glycero-galacto-2-nonulosonic acid is alpha 3 bonded to the second galactose [0077]
With respect to claim 8, Cummings et al. teach the polysaccharide is sialyl Lewis X or sialyl Lewis A [0047].
With respect to claims 10-11, Veronese teaches amino groups, namely the alpha amino or the epsilon amino of lysine, are the usual sites of PEG linking (p407, col 1, para 1). It is noted that the elected peptide species of SEQ ID NO: 12 has only a single N-terminal lysine residue comprising amine groups.
With respect to claim 14, Veronese shows PEGylation peptide comprising a linking moiety of C(O) moiety and m=0 in Fig. 3 (p407).
With respect to claim 24, Cummings et al. teach the composition comprising a glycopeptides and a pharmaceutically acceptable excipient [0101].
Applicant’s Arguments
Application discloses PG-6 (KEFEFLDFDFLPETEPL), a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation, demonstrating the exceptional in vitro and in vivo activity of the claimed PEGylated glycopeptides would not have been expected in view of Veronese. Furthermore, "PEGylation of a negatively charged glycopeptide bearing a complex polysaccharide has yet to be reported. Few if any established protocols exist for either the synthesis or purification of such compounds." Paragraph [00271].
Response to Arguments
Applicant's arguments (Remarks, p11 to p12, para 1-2) filed 4/17/2026 have been fully considered but they are not persuasive because (1) the single peptide sequence of PG-6 as argued by applicant is not commensurate in scope with the peptide formula of SEQ ID NO: 1 in the base claim 1, (2) Cummings et al. suggest the use of the peptide sequence of SEQ ID NO: 12 (claim 12) for treating various diseases (claim 17) including inhibiting P-selectin/PSGL-1 dependent interaction in vitro and leukocyte rolling in vivo [0138-0139] and thrombus formation (claims 17-18), (3) Veronese teaches advantages of PEG conjugation comprising increase of the molecular size for a small polypeptide to reduce its renal ultrafiltration, reducing the degradation by proteolytic enzymes and modifying biodistribution and solubility of the PEGylated peptide (p406, col 1, para1). Expected beneficial results are evidence of obviousness. See MPEP 716.02(c).
2. Claims 1, 3-5, 7-11, 13-14, 24, and 42-43 are rejected under 35 U.S.C. 103 as being unpatentable over Cummings et al. in view of Veronese as applied to claims 1, 3-5, 7-11, 14, 24, and further in view of Roberts et al. (Advanced Drug Delivery Reviews 54 (2002) 459-476).
Claim 13 is drawn to the PEG terminates in one or more hydroxy or alkoxy end groups.
Cummings et al. in view of Veronese teach a PEGylated glycopeptide composition as applied to claims 1, 3-5, 7-9, 14, and 24.
Cummings et al. in view of Veronese did not specify the PEG terminates in one or more hydroxy or alkoxy end groups.
Similarly, Roberts et al. teach that PEG conjugation increases the apparent size of the polypeptide, thus reducing the renal filtration and altering biodistribution as well as prevents recognition and degradation by proteolytic enzymes well known in the art (Abstract). Roberts et al. teach the most common reactive groups involved in coupling PEG to a peptide are the alpha or epsilon amino groups of lysine for PEGylation well-known in the art (p462, col 2, 3.1.1. PEG chemistry for amine conjugation) shown in Fig. 1 (p463), consistent with Veronese’s teaching above. Roberts et al. teach most common form poly(ethylene glycol), PEG, is a linear or branched polyether terminated with hydroxyl groups and most useful for polypeptide modification is monomethoxy PEG, mPEG, as CH3O-(CH2CH2O)n-CH2CH2-OH (p460, col 2, 2. Properties of PEG), reading on the PEG terminates in an alkoxy end group of OCH3.
Because Roberts et al. teach most common form poly(ethylene glycol), PEG, is a linear or branched polyether terminated with hydroxyl groups and most useful for polypeptide modification is monomethoxy PEG, mPEG, one of ordinary skill in the art would have found it obvious to use PEG terminates in either hydroxy or alkoxy (preferred) as taught by Roberts et al.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Cummings et al. in view of Veronese with Roberts’s PEG for PEGylation because (a) Cummings et al. in view of Veronese teach PEGylation of a small glycopeptide at lysine residue and (b) Roberts et al. teach PEG can terminates in either hydroxy or alkoxy but most useful for polypeptide modification is monomethoxy PEG, mPEG, (p460, col 2, 2. Properties of PEG). The combination would have reasonable expectation of success because both references of Veronese and Roberts et al. teach peptide PEGylation.
With respect to claims 42-43, Roberts et al. teach PEG terminates in an alkoxy end group of OCH3, CH3O-(CH2CH2O)n-CH2CH2-OH (p460, col 2, 2. Properties of PEG). Veronese teaches the distance between the active ester (-COOSu) and the last PEG ether can vary in different available products, by up to four methylene units, (-CH2-)4, and this has profound influence on the reaction towards amino groups as well towards water (p407, col 2, para 1; p407, Fig 3a), reading on n = 0 to 4. Since the only amine reactive group is localized to the N-terminal lysine residue of SEQ ID NO: 12 (K*EY1EY2LDY3DFLZ1EW1EPL), the PEG is conjugated to the first lysine residue of SEQ ID NO: 12 via an amine group shown as follows.
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Response to Arguments
Applicant's arguments (Remarks, p11 to p12, para 3-4) filed 4/17/2026 have been fully considered but they are not persuasive. The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992) as described in MPEP 2144(I). Also see response to arguments above.
3. Claims 1, 3-5, 7-12, 14, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Cummings et al. in view of Veronese as applied to claims 1, 3-5, 7-11, 14, 24 and further in view of O’Connor et al. (Molecules. 2014, 19, 17559-17577).
Claim 12 is drawn to the number of conjugated PEG monomer between 20 and 3,500.
Cummings et al. in view of Veronese teach a PEGylated glycopeptide composition as applied to claims 1, 3-5, 7-9, 14, and 24.
Cummings et al. in view of Veronese did not specify a number of conjugated PEG monomers between 20 and 3,500.
O’Connor et al. teach “Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities” (Title). O’Connor et al. teach functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities (Abstract). O’Connor et al. teach the repeating units of synthetic polymer (e.g., PEG) for peptide conjugate is a result effective variable depending on the peptide sequence and suggest be repeating unit of PEG can be optimized between 20 to 50 (p17560, last para to p17561, para 1), reading on claim 12.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Cummings et al. in view of Veronese with O’Connor’s teach repeating units pf PEG for peptide conjugation because (a) Cummings et al. in view of Veronese teach PEGylation of a small glycopeptide at lysine residue and (b) O’Connor et al. teach functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities (Abstract). O’Connor et al. teach the repeating units of synthetic polymer (e.g., PEG) for peptide conjugate is a result effective variable depending on the peptide sequence and suggest be repeating unit of PEG can be optimized between 20 to 50 (p17560, last para to p17561, para 1). The combination would have reasonable expectation of success because both Veronese and O’Connor et al. teach peptide PEGylation.
Response to Arguments
Applicant's arguments (Remarks, p12, last para to p13, para 1) filed 4/17/2026 have been fully considered but they are not persuasive. See response to arguments above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-5, 7-9, 13-14, 24, and 42-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12, and 14 of U.S. Patent No. 10,253,071 B2 (the ‘071 patent, cited in IDS) in view of Cummings et al. (US 2016/0108092 A1) in view of Veronese (Biomaterials 22 (2001) 405-417).
Claims 1-3 the ‘071 patent disclosed the instant peptide formula of SEQ ID NO: 1.
Claim 4 of the ‘071 patent disclosed polysaccharide is sialyl Lewis X or sialyl Lewis A.
Claims 5-9 of the ‘071 patent disclosed the polysaccharide structures
Claim 12 of the ‘071 patent disclosed the instant glycopeptide sequences of SEQ ID Nos: 2-12.
Claim 14 of the ‘071 patent disclosed a pharmaceutical composition comprising a glycopeptide of claim 1 and a pharmaceutically acceptable excipient.
Claims 1-9, 12, and 14 the ‘071 patent did not disclose PEGylation of the glycopeptide.
The relevancy of Cummings et al. in view of Veronese as applied to claims 1, 3-5, 7-9, 14, and 24 described above not repeated here.
Because Cummings et al. in view of Veronese teach benefits of PEGylation for small peptide, one of ordinary skill in the art would have found it obvious to perform PEGylation of the small glycopeptides taught by claims 1-9, 12, and 14 the ‘071 patent.
Thus, claims 1-9, 12, and 14 the ‘071 patent in view of Cummings et al. in view of Veronese are obvious to the instant claims 1, 3-5, 7-9, 13-14, 24, and 42-43.
Response to Arguments
Applicant's arguments (Remarks, p13, Double Patenting Rejections, para 1-2) filed 4/17/2026 have been fully considered but they are not persuasive. See response to arguments above.
Claims 1, 3-5, 7-9, 13-14, 24, and 42-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12, and 14 of U.S. Patent No. 12,162,960 B2 (the ‘960 patent) in view of Cummings et al. (US 2016/0108092 A1) in view of Veronese (Biomaterials 22 (2001) 405-417).
Claim 1 of the ‘960 patent disclosed a glycopeptide composition comprising SEQ ID Nos: 4 or 8-12.
Claim 2 of the ‘960 patent disclosed polysaccharide is sialyl Lewis X or sialyl Lewis A.
Claims 3-7 of the ‘960 patent disclosed polysaccharide structures on the glycopeptide.
Claim 11 of the ‘960 patent disclosed the elected glycopeptide sequence of Seq ID NO: 12.
Claims 1-7 and 11 the ‘960 patent did not disclose PEGylation of the glycopeptide.
The relevancy of Cummings et al. in view of Veronese as applied to claims 1, 3-5, 7-9, 14, and 24 described above not repeated here.
Because Cummings et al. in view of Veronese teach benefits of PEGylation for small peptide, one of ordinary skill in the art would have found it obvious to perform PEGylation of the small glycopeptides taught by claims 1-7 and 11 the ‘960 patent.
Thus, claims 1-7 and 11 the ‘960 patent in view of Cummings et al. and Veronese are obvious to the instant claims 1, 3-5, 7-9, 13-14, 24, and 42-43.
Response to Arguments
Applicant's arguments (Remarks, p13, Double Patenting Rejections, para 1-2) filed 4/17/2026 have been fully considered but they are not persuasive. See response to arguments above.
Claims 1, 3-5, 7-9, 14, and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 16 of copending Application No. 18/693,494 (the ‘494 application, 3/19/2024) in view of Cummings et al. (US 2016/0108092 A1) and Veronese (Biomaterials 22 (2001) 405-417).
Claims 1 and 16 of the ‘494 application disclosed the instant glycopeptide of SEQ ID Nos: 2-12.
Claim 2 of the ‘494 application disclosed the polysaccharide structure of the glycopeptide.
Claims 1-2 and 16 the ‘494 application did not disclose PEGylation of the glycopeptide.
The relevancy of Cummings et al. in view of Veronese as applied to claims 1, 3-5, 7-9, 14, and 24 described above not repeated here.
Because Cummings et al. in view of Veronese teach benefits of PEGylation for small peptide, one of ordinary skill in the art would have found it obvious to perform PEGylation of the small glycopeptides taught by claims 1-2 and 16 the ‘494 application.
Thus, claims 1-2 and 16 the ‘494 application in view of Cummings et al. and Veronese are obvious to the instant claims 1, 3-5, 7-9, 14, and 24.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments (Remarks, p13, last para to p14, para 1-3) filed 4/17/2026 have been fully considered but they are not persuasive because (a) the examiner use Cummings et al. (US 2016/0108092 A1) in view of Veronese (Biomaterials 22 (2001) 405-417) for the ODP rejection and all the teachings in the qualified prior art references can be used for ODP rejection, and (b) this is a provisional rejection neither Cummings et al. (US 2016/0108092 A1) nor Veronese copending with the ‘494 application.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/J.L/Examiner, Art Unit 1658
02-June-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights