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 24, 26, 29-46 are pending.
Claims 1-23, 25, and 27-28 are cancelled.
Claims 31-35 are withdrawn as being directed to a non-elected species. Claims 36-46 are further withdrawn as directed to a non-elected method invention the election having been made on 7/1/2025.
Claims 24, 26, and 29-30 have been examined.
Priority
This application is a 371 of PCT/KR2021/001282 02/01/2021
KOREA, REPUBLIC OF 10-2020-0014941 02/07/2020
New Ground of Objection and Rejection
Claim Objections
Claims 24 and 30 are objected to because of the following informalities:
With respect to claim 24, the phrase “..is bound to the N-terminal of the peptide” should be “..is bound to the N-terminus of the peptide”.
With respect to claim 30, the claim contains the acronym “IL-8”, and an acronym in the first instance of claims should be expanded upon/spelled out as “interleukin-8” with the acronym indicated in parentheses as (IL-8). The abbreviations can be used thereafter.
Appropriate correction of the grammar error is required.
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.
Claims 24, 26, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2017/0158761 A1, previously cited 7/29/2025) in view of Veronese et al. (Biodrugs. 2008; 22 (5): 315-329, previously cited 7/29/2025).
Claim 1 is drawn to a PEGylated peptide of (PEG5-10 kDa)-W-Y-V-Y-P-S-M (SEQ ID NO: 2) and PEG functionalized by an aldehyde group for reacting to the N-terminal amine group of the peptide.
Lee et al. teach a receptor binding domain of an IgE-dependent histamine releasing factor/HRF (Abstract) isolated by phage display [0260] with a peptide sequence of WYVYPSM/SEQ ID NO: 24 [0262]. Lee et al. further teach the peptide able to inhibit IL-8 secretion [Abstract; p5, 0093, last 5 lines].
Lee et al. do not teach PEGylation of the peptide.
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Veronese et al. teach PEGylation resulting in improvement in the pharmacokinetic behavior of the drug comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract). Veronese et al. show PEG (polyethylene glycol) functionalized with aldehyde for site-specific conjugation to the amine group of a protein/peptide known to one of ordinary skill in the art shown above (p318, Fig. 2b). Veronese et al. further show the molecular weight of PEG 5 kDa for protein/peptide conjugation has been approved by US FDA for human use (p318, Table II).
Because (i) Veronese et al. teach various advantages of PEGylation and a protein/peptide conjugated with 5 kDa PEG approved by US FDA for human use (Abstract; p318, Table II), (ii) Veronese et al. show PEG (polyethylene glycol) functionalized with aldehyde for site-specific conjugation to the amine group of a protein/peptide known to one of ordinary skill in the art (p318, Fig. 2b) and (iii) the only reactive amine group of Lee’s therapeutic peptide WYVYPSM/SEQ ID NO: 24 [0262] is the N-terminal amine group of W residue, one of ordinary skill in the art would at once envisage to beneficially conjugate Veronese’s PEG-C(O)H (e.g., 5 kDa) to Lee’s peptide of NH2-WYVYPSM to generate a PEGylated peptide of PEG5kDa-WYVYPSM as claimed.
One of ordinary skill in the art before the effective fining date of this invention would have found it obvious to combine (i) Lee’s HRF-binding peptide with (ii) Veronese’s PEG because (a) Veronese et al. teach various advantages of PEGylation of a peptide (Abstract), (b) Veronese et al. show PEG functionalized by an aldehyde group for site-specific conjugation to the amine group of a peptide (p318, Fig 2b), and (c) the molecular weight of 5 kDa PEG for protein/peptide conjugation has been approved by US FDA for human use (p318, Table II). The combination would have reasonable expectation of success because Veronese et al. teach advantages of PEGylation of peptide known in the art (Abstract) and the molecular weight of 5 kDa PEG for protein/peptide conjugation has been approved by US FDA for human use (p318, Table II).
With respect to claim 26 and 29, Veronese et al. show PEG (polyethylene glycol) functionalized with aldehyde for site-specific conjugation to the amine group of a protein/peptide known to one of ordinary skill in the art shown above (p318, Fig. 2b). The only reactive amine group of Lee’s therapeutic peptide consisting of WYVYPSM/SEQ ID NO: 24 [0262] is the N-terminal amine group of W residue.
With respect to claim 30, Lee et al. teach the HRF-binding peptide of WYVYPSM able to inhibit IL-8 secretion [Abstract; p5, 0093, last 5 lines].
Applicant’s Arguments
The claim amendment and arguments overcomes the rejection of record for the reasons as follows:
No motivation to limit the molecular weight of PEG having an aldehyde functional group to the specific range of 5 to 10 kDa because (i) Lee does not make any reference to pegylation of the peptide and (ii) there is also no motivation in Veronese to limit the molecular weight of PEG having an aldehyde functional group to 5 to 10 kDa as required by the presently amended claims (Remarks, p6, last two para to p8, para 1-6).
(B) The currently claimed dTBP2 peptide (WYVYPSM - SEQ ID NO:2) pegylated at the N-terminus with PEG of 5-10 kDa and having an aldehyde functional group exhibits unexpected functional improvement according to data/arguments a-f (Remarks, p8, last para to p13, para 1-3).
(C) One skilled in the art would not have been able to predict the effect of pegylation on
the currently claimed peptide with a 5-10 kDa PEG having an aldehyde functional group
at the N-terminus based on the combination of Lee and Veronese according to Harris (Nature 2003, 2: 214-221) and figure 7 (Remarks, p13, last para to p15, para 1-2).
Response to Arguments
Applicant's arguments filed 10/24/2025 have been fully considered but they are not persuasive for the reasons as follows.
Applicant’s argument A is not persuasive because applicant’s arguments against the references of Lee and Veronese individually whereas the rejection is based on Lee in view of Veronese as a whole. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In particular, Veronese et al. teach (i) various advantages of PEGylation of a peptide (Abstract), (ii) PEG functionalized by an aldehyde group for site-specific conjugation to the amine group of a peptide (p318, Fig 2b), and (iii) Veronese et al. further show the molecular weight of 5 kDa PEG for protein/peptide conjugation has been approved by US FDA for human use (p318, Table II). Any one or a combination of Veronese’s teachings described above provide teaching, suggestion, and motivation for PEGylation of 5 kDa PEG functionalized with aldehyde for conjugation to the N-terminus of WYVYPSM.
Applicant’s argument B is not persuasive because there is no unexpected result. Veronese et al. teach PEGylation resulting in improvement in the pharmacokinetic behavior of the drug comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract). Veronese et al. show PEG (polyethylene glycol) functionalized with aldehyde for site-specific conjugation to the amine group of a protein/peptide known to one of ordinary skill in the art shown above (p318, Fig. 2b). Veronese et al. further show the molecular weight of PEG at 5 kDa for protein/peptide conjugation has been approved by US FDA for human use (p318, Table II). It is noted that the only reactive amine group of Lee’s therapeutic peptide WYVYPSM/SEQ ID NO: 24 [0262] is the N-terminal amine group of W residue.
Response to Applicant’s data/arguments a-f as follows:
Applicant’s data/arguments (a) is not persuasive because Veronese et al. teach the use of PEG hydrazide, which is reactive at low pH as an amino donor. However, to date, no useful application has been found (p319, col 2, Sec 3.4, para 1). One the other hand, Veronese et al. show PEG (polyethylene glycol) functionalized with aldehyde for site-specific conjugation to the amine group of a protein/peptide known to one of ordinary skill in the art shown above (p318, Fig. 2b). Veronese et al. further show the molecular weight of PEG at 5 kDa for protein/peptide conjugation has been approved by US FDA for human use (p318, Table II). It is noted that the only reactive amine group of Lee’s therapeutic peptide WYVYPSM/SEQ ID NO: 24 [0262] is the N-terminal amine group of W residue. Thus, one of ordinary skill in the art would expect to use 5 kDa PEG (polyethylene glycol) functionalized with aldehyde for site-specific conjugation to the amine group of Lee’s therapeutic peptide WYVYPSM/SEQ ID NO: 24, not using PEG (polyethylene glycol) functionalized with hydrazide as argued by applicant.
Applicant’s data/arguments (b)-(d) are not persuasive because Veronese et al. teach PEGylation resulting in improvement in the pharmacokinetic behavior of the drug comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract). Thus, it is expected that a PEGylated peptide/protein is more effective that a peptide/protein without PEGylation.
Applicant’s data/argument (e) is not persuasive because the rejection is based on 5 kDa PEG conjugated peptide not 10 kDa PEG conjugated peptide. Furthermore, The data comparison of Examples 3 and 4 in Fig 18 shows significantly overlapping of the error bar range, suggesting the data do not have statistical and practical significance. The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). See MPEP 716.02(b).
Applicant’s data/argument (f) is not persuasive because Veronese et al. teach PEGylation resulting in improvement in the pharmacokinetic behavior of the drug comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract), demonstrating the benefit of PEGylation to a peptide as argued by applicant is expected and known in the art.
Applicant’s argument C is not persuasive because Veronese et al. teach PEGylation resulting in improvement in the pharmacokinetic behavior of the drug comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract), not limiting to enhance the function of peptide as argued by applicant. Harris et al., provided by applicant, teach pegylation of a polypeptide is expected to lower its renal clearance, increase its half-life and improve its biological activity. Harris et al. teach the most common reactive sites on polypeptides for attaching PEG polymers are the α or ε amino groups of lysine or the N-terminal amino-acid groups of other amino acids (p215, col 2, para 2). It is noted that the only reactive amine group of Lee’s therapeutic peptide WYVYPSM/SEQ ID NO: 24 [0262] is the N-terminal amine group of W residue. In contrast to applicant’s argument C, the reference of Harris et al. provided by applicant is consistent with the combined teachings of Lee et al. in view of Veronese et al. described in the rejection above as well as response to arguments A and B above, not repeated here. Expected beneficial results are evidence of obviousness. See MPEP 716.02(c).
Conclusion
No claim is allowed.
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-February-2026
/LI N KOMATSU/ Primary Examiner, Art Unit 1658