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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/4/2026 has been entered.
Claim Status
Claims 24 and 29-46 are pending.
Claims 1-23, 25-26, 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Claims 31-35 are withdrawn as being directed to a non-elected species. Claims 36-46 are further withdrawn as directed to a non-elected method invention the election having been made on 7/1/2025.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 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
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/4/2026 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Withdrawn Objection
The objection to claims 24 and 30 is withdrawn because the amendment to claims 24 and 30 overcomes the objection.
New Ground of rejection
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 24 and 29-30 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 24 is unclear with respect to the last two wherein clauses as shown follows.
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A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 24 recites the broad recitation PEG covalently linked to a carboxylic or an amino of the HRF-binding peptide in the last wherein clause, and the claim also recites PEG bound to the N-terminus of the HRF-binding peptide in the 2nd last wherein clause which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 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).
The broadest claim interpretation of claim 1 is drawn to a PEGylated peptide of (PEG5-10 kDa)-(aldehyde) covalently linked to a peptide comprising W-Y-V-Y-P-S-M (SEQ ID NO: 2) at either amino or carboxylic group of the peptide comprising SEQ ID NO:2.
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.
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
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in the art as shown follows (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) in addition to the advantages
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of protein/peptide PEGylation as taught by Veronese et al.
Because (i) Veronese et al. suggest (a) advantages of peptide/protein PEGylation with 5 KDa PEG comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract), (b) FDA approved the beneficial use of 5 KDa PEG for peptide/protein conjugation for human use (p318, Table II), (i)(c) PEG functionalized with aldehyde for site-specific conjugation to the amine group of a peptide/protein and (ii) Lee’s peptide W-Y-V-Y-P-S-M (SEQ ID NO: 2) contains a single reactive amino group at the N-terminus of W residue able to react to Veronese’s aldehyde functionalized PEG, one of ordinary skill in the art would have found it obvious to use Veronese’s aldehyde-functionalized PEG for site-specific conjugation to Lee’s peptide W-Y-V-Y-P-S-M (SEQ ID NO: 2).
One of ordinary skill in the art before the effective fining date of this invention would have found it obvious to beneficially combine (i) Lee's HRF-binding peptide with (ii) Veronese's PEG because Veronese et al. suggest (a) advantages of peptide/protein PEGylation with 5 KDa PEG comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract) and (b) Veronese et al. show FDA approved beneficial use of 5 KDa PEG for peptide/protein conjugation for human use (p318, Table II), and (c) Veronese et al. show PEG functionalized by an aldehyde group for site-specific conjugation to the amine group of a peptide (p318, Fig 2b). The combination would have reasonable expectation of success because Veronese et al. show PEG functionalized by an aldehyde group for site-specific conjugation to the amine group of a peptide (p318, Fig 2b) with one or more advantages as suggested by Veronese et al. (Abstract).
With respect to claim 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 (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.
Applicant’s Arguments
One skilled in the art would also expect PEGylation to cause a reduction of biological activity due to steric hindrance as a disadvantage (Remarks, p7, para 1). In contrast, The PEGylated dTBP2 in Example 2 exhibits higher biological activity than nonPEGylated dTBP2 in figure 7 (Remarks, p7, para 1-2).
In view of Veronese, one skilled in the art would reasonably expect PEGylation of a peptide to result in reduction of the biological activity of the conjugated peptide because (a) Veronese clearly demonstrates that PEGylation is known in the art to inherently include the possibility of reducing biological activity and (b) Veronese presents three PEGylated proteins’ thus, PEGylation of any proteins will cause reduction of biological activity. Furthermore, Harris teaches that changes in the size, structure, and molecular weight of PEG polymers are known to affect biological activity (Remarks, p7, last 3 para to p9, para 1-3).
One skilled in the art would have predicted that it would have been even more difficult to maintain biological activity as a result of PEGylation in ultra-short peptides such as those utilized in the present claims (Remarks, p9, last para to p11, para 1-3)
The present invention provides increased biological activity in a PEGylated 7-mer peptide, which would not have been expected by one skilled in the art (Remarks, p11, last 3 para to p13, para 1-2).
Response to Arguments
Applicant's arguments filed 5/4/2026 have been fully considered but they are not persuasive for the reasons as follows.
Applicant’s argument (1) is not persuasive because (a) Veronese et al. teach PEGylation of a protein/polypeptide can increase activity such as PEGylated trypsin and PEGylated amino oxidase (p322, col 2, 5. Biological Consequences of PEGylation, para 1), not limited to reduction of biological activity as argued by applicant. Furthermore, Veronese et al. teach the beneficially extended pharmacokinetics of a PEGylated protein/peptide (e.g., PEG-IFNα-2a) overcome its reduced in vitro potency, giving rise to more prolonged in vivo activity. Once-weekly administration with either PEGylated form was found to produce significantly higher rates of viral eradication than the parent IFNα administered three times weekly (p323, col 2, para 2). In addition, PEGylation decreased the antagonistic activity of B2036 by about 28-fold, but the effect was balanced by the much improved plasma half-life (p324, col 1, para 1). Thus, one of ordinary skill in the art would have been taught that the benefit of PEGylation of a polypeptide/protein is greater that loss of bioactivity as argued by applicant. Furthermore, Veronese et al. suggest (a) advantages of peptide/protein PEGylation with 5 KDa PEG comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract) and (b) FDA approved the beneficial use of 5 KDa PEG for peptide/protein conjugation for human use (p318, Table II). The expectation of some advantage of peptide/protein PEGylation as taught by Veronese et al. is the strongest rationale for combining references (See MPEP 2144 II) and it is not necessary that the prior art suggests the combination to achieve the same advantage or result discovered by applicant (See MPEP 2144 IV).
Applicant’s argument (A) is not persuasive because Veronese et al. teach PEGylation of a protein/polypeptide can increase activity such as PEGylated trypsin and PEGylated amino oxidase (p322, col 2, 5. Biological Consequences of PEGylation, para 1), not limited to reduction of biological activity as argued by applicant. The argument logic of PEGylation of a protein “inherently” reduces the biological activity of the conjugated peptide is merely applicant’s opinion and deviates from the fact of Veronese’s teaching. Thus, any conclusion based on a wrong argument logic deviated from the fact is not persuasive.
Applicant’s argument (B) is not persuasive because Veronese et al. teach the beneficially extended pharmacokinetics of a PEGylated protein/peptide (e.g., PEG-IFNα-2a) overcome its reduced in vitro potency, giving rise to more prolonged in vivo activity. Once-weekly administration with either PEGylated form was found to produce significantly higher rates of viral eradication than the parent IFNα administered three times weekly (p323, col 2, para 2). In addition, PEGylation decreased the antagonistic activity of B2036 by about 28-fold, but the effect was balanced by the much improved plasma half-life (p324, col 1, para 1). Thus, one of ordinary skill in the art would have been taught that the benefit of PEGylation of a polypeptide/protein is greater that loss of bioactivity as argued by applicant. The reasons to combine cited references comprises (a) advantages of peptide/protein PEGylation with 5 KDa PEG comprising improving drug solubility, decreasing immunogenicity, increasing drug stability, retention time in blood, and reducing dosing frequency known in the art (Abstract), (b) FDA approved the beneficial use of 5 KDa PEG for peptide/protein conjugation for human use (p318, Table II), and (c) PEG functionalized with aldehyde for site-specific conjugation to the amine group of a peptide/protein; therefore, applicant’s opinion of losing bioactivity of PEGylation, not a cited reason to combine the references, does not overcome the rejection based on the cited reasons of record. It is not necessary that the prior art suggests the combination to achieve the same advantage or result discovered by applicant. See MPEP 2144 IV.
Applicant’s argument (C) is not persuasive because the data is not commensurate in scope of the rejected claims as the claim scope is much broader to be supported by the data. Furthermore, prima facie obviousness is not rebutted by merely recognizing additional advantages or latent properties present but not recognized in the prior art. See MPEP 2145 (II).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIA-HAI LEE whose telephone number is (571)270-1691. The examiner can normally be reached Mon-Fri from 9:00 AM to 6:00 PM.
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/J.L/Examiner, Art Unit 1658
11-July-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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