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 .
Claims 1, 3-15, 17 and 25-28 are pending and examined on the merits after amendments.
Applicant’s response (amendments with arguments simply referring to the amendments as traversing the rejecitons) is acknowledged.
See also Interview Summary (Attached). The claim amendments have been weighed against the preamble language, and support/description and raise new modified issues that must be addressed on the record with follow-up amendment and/or arguments.
The examiner remains open to further interview to advance prosecution on the merits.
Election/Restrictions - Maintained as Species, Withdrawn as to Group (Withdrawn Claims Cancelled)
Applicant’s election without traverse of Group I, claims 1-18, as drawn to the elected peptide species Pep-45 (below), in the reply filed on 9/15/21 is acknowledged:
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The Claimed Invention – Previously Noted
The claimed method relates to the cyclization of a peptide (elected species Pep-45, see above) via an amide bond formed from the reaction of a first reaction point with a second reaction point in the peptide synthesized by translating a nucleic acid encoding a noncyclic peptide, and the amino acid residue of formula I or II (claim 1) having the first reaction point.
Allowable Subject Matter – Pending Resolution of Remaining Rejections
A method as claimed of producing the elected peptide of Pep-45 was not found to be reasonably taught or suggested by the prior art of record:
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Applicant’s prior work, now U.S. Patent No. 9,409,952 (applicant’s earlier work) is deemed the closest art of record, but does not teach producing Pep-45.
It is noted that the international authority found the same in the related PCT.
Claim Rejections - 35 USC § 112(b)-Maintained, Modified,
Preamble v. Amended Claim Scope; Modified Necessitated by Amendment
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.
Claims 1, 3-15, 17 and 25-28 remain 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.
The claims are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite as to the phrase “unnatural amino acid residues” (replacing amino acid analog residues) (see claim 1, line 2), as the claims do not set forth the metes and bounds of where the “two or more” thereof may be positioned within the constructures – rendering such indefinite as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: 1) unnatural amino acids (two or more) may be anywhere except at the N-terminus; and 2) both the thiol near the N-terminus and the N-terminal amide must be positively claimed as protected. Until the critical/essential elements of the claimed invention have all been positively claimed a reasonably search of the prior art of record cannot be carried out.
See for example, PGPUB U.S. 20190338050, relevant passages that at a minimum such may not be at or attached to the N-terminus – a critical/essential limitation that must be set forth in the next amendments:
[0217] Exemplary unnatural amino acids (amino acid analogs) that can be used other than at the N terminus in the present invention are shown below; however, the unnatural amino acids are not limited thereto. Many of these unnatural amino acids can be purchased with their side chains protected or unprotected and their amine moieties protected or unprotected. Those that cannot be purchased can be synthesized by known methods.
Critical/Essential Elements of Inventive Concept – Suggestion for Further Amendment Thereto:
[E.g. Including to distinguish applicant’s earlier work described in the specification as Patent Document 1 and the closet prior art of record: Chugai S.K.K. WO2013100132 (2013 Publ.)]
Abstract
When the initiation suppression method was used for translation of a peptide having at its N terminus an amino acid residue carrying a thiol group near its amino group with specific protecting groups being introduced to the thiol group and the amino group, it was found that not only the probability of initiation of amino acid translation reaction was improved, but also production of cleaved peptides was suppressed and translation efficiency and purity were improved. Furthermore, it was found that it is possible to efficiently promote the cyclization reaction of the peptide through amide bond formation. Based on these findings, the inventors discovered novel methods for preparing complexes between nucleic acids and peptides containing various unnatural amino acids and having an amide bond-mediated cyclized portion.
Background/Summary
[0001] The present invention relates to establishment of techniques for efficient translation of peptides and complexes of the peptides and nucleic acids, the peptides comprising a plurality of amino acid analogs, in which an amino acid carrying a thiol group near its amino group is positioned at the N-terminus. The present invention also relates to methods for producing peptides having a cyclic portion containing a plurality of amino acid analogs, complexes of the peptides and nucleic acids, and libraries containing the complexes.
[ ]
[0028] The present invention was achieved in view of the above-described problems. An objective of the present invention is to provide efficient translation techniques for peptides comprising a plurality of amino acid analogs, in which an amino acid residue carrying a thiol group near its amino group is positioned at the N-terminus. Furthermore, an objective of the present invention is to provide methods for preparing peptides having a cyclic portion which contains a plurality of amino acid analogs and has an amide bond-cyclized moiety, complexes of the peptides and nucleic acids, and libraries containing the complexes.
[0029] The present inventors elucidated that the translation initiation method, which has been assumed to be not directly involved in translation elongation reaction, affects the translation efficiency of amino acid analogs in the downstream of translation, the purity of the products, and the production of cleaved peptides which are impurities. These facts could not be detected through conventional evaluation methods (i.e., evaluation using peptides composed of naturally-occurring amino acids except for the N terminus), but was able to be detected for the first time through evaluation using peptides containing a plurality of amino acid analogs.
[0030] More specifically, under the coexistence of various functional groups in peptides or peptide-nucleic acid complexes, the present inventors carried out translation using the iSP method for a peptide having at the N terminus an amino acid residue carrying a thiol group near its amino group with both the thiol group and the amino group being protected by a specific protecting group that can be selectively and quantitatively deprotected, and elucidated that the probability of initiation of the translation reaction increases, production of cleaved peptides is suppressed, and translation efficiency and purity are improved. Furthermore, the present inventors discovered novel methods for producing peptides having cyclized moieties and complexes of the peptides and nucleic acids, the methods enabling efficient cyclization of peptides obtained by using the iSP method and peptide moieties of the complexes of the peptides and nucleic acids, and completed the present invention.
Previously relevant sections thereto:
[0188] “Amino acid analogs” include unnatural amino acids (for example, unnatural α-amino acids, β-amino acids, and γ-amino acids). An α-amino acid may be a D-amino acid, or an α,α-dialkylamino acid. In a similar manner to an α-amino acid, a β-amino acid and a γ-amino acid are also allowed to have any configuration. A side chain (with the main chain being methylene) of the amino acid analogs is not particularly limited, and may have, besides hydrogen atoms, for example, an alkyl, an alkenyl, an alkynyl, an aryl, a heteroaryl, an aralkyl, or a cycloalkyl. Each of these may have one or more substituents, and these substituents can be selected from any functional group containing, for example, a halogen atom, an N atom, an O atom, an S atom, a B atom, a Si atom, or a P atom. For example, herein, “C1-C6 alkyl optionally substituted with halogen” means “C1-C6 alkyl” substituted with one or more halogen atoms, and specific examples include trifluoromethyl, difluoromethyl, fluoromethyl, pentafluoroethyl, tetrafluoroethyl, trifluoroethyl, difluoroethyl, fluoroethyl, trichloromethyl, dichloromethyl, chloromethyl, pentachloroethyl, tetrachloroethyl, trichloroethyl, dichloroethyl, and chloroethyl. Furthermore, for example, “optionally substituted C5-C10 aryl C1-C6 alkyl” means that in which at least one hydrogen atom of the aryl and/or alkyl of “C5-C10 aryl C1-C6 alkyl” has been substituted with a substituent. Furthermore, “cases having two or more substituents” include cases having an S atom-containing functional group, which further has functional groups such as an amino or a halogen.
[0189] The main chain amino group of an amino acid analog may be unsubstituted (a NH.sub.2 group), or it may be substituted (that is, an NHR group; in which R represents an alkyl, an alkenyl, an alkynyl, an aryl, a heteroaryl, an aralkyl, or a cycloalkyl, each of which optionally has a substituent; or a carbon chain bonded to the N atom and a carbon atom at the a position may form a ring as in proline. The substituent is similar to the substituent of the side chain, and examples include a halogen, an oxy, and a hydroxy.). Furthermore, for “an alkyl, an alkenyl, an alkynyl, an aryl, a heteroaryl, an aralkyl, or a cycloalkyl” in the definition of these substituents, the above-mentioned definitions for these functional groups are applied. For example, herein, “alkoxy” means a group in which a hydrogen atom in a hydroxy group is replaced with the above-mentioned alkyl group. Preferred examples thereof include “C1-C6 alkoxy”.
[0190] Furthermore, “amino acid analogs” include hydroxycarboxylic acids in which an amino group of an “amino acid” has been replaced with a hydroxyl group. The hydroxycarboxylic acid may have various substituents, in a similar manner to other amino acid analogs. The hydroxycarboxylic acid may have a configuration corresponding to either an L- or D-form amino acid. While its side chain is not particularly limited, for example, it is selected from an alkyl, an alkenyl, an alkynyl, an aryl, a heteroaryl, an aralkyl, a cycloalkyl, and such, which are optionally substituted.
[ ]
[0217] Exemplary unnatural amino acids (amino acid analogs) that can be used other than at the N terminus in the present invention are shown below; however, the unnatural amino acids are not limited thereto. Many of these unnatural amino acids can be purchased with their side chains protected or unprotected and their amine moieties protected or unprotected. Those that cannot be purchased can be synthesized by known methods.
Prior Art Made of Record But Not Relied Upon – Previously Noted
U.S. Patent No. 9,409,952
U.S. Patent No. 11,891,457
U.S. Patent No. 12,415,835
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 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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/MAURY A AUDET/Primary Examiner, Art Unit 1654
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