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 .
Election/Restrictions
Applicant’s election without traverse of Species A (i.e., compound C01 with the structure:
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as a single and specific peptide compound, which is a cyclic peptide of 11 amino acids in length and contains
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as an amino acid capable of forming a hydrogen bond in a side chain) in the reply filed on April 14, 2025, is acknowledged.
Please note that the elected peptide compound is free of the art as there is no teaching or suggestion to achieve structure of the full peptide compound. The elected amino acid is free of the prior art notwithstanding the obviousness-type double patenting rejection below. Also, please note that in light of the Examiner’s search, the single and specific amino acid is expanded to include:
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and
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Moreover, please note that Applicants did not elect a protecting group, and thus, the Examiner is interpreting Applicant’s election as not having a protecting group.
Status of Claims
Claims 1-16 were originally filed on June 9, 2021.
The amendment received on February 8, 2022, amended claims 3, 5-6, 8-12, and 15. The amendment received on October 16, 2025, canceled claims 3-4 and 13; amended claims 1-2 and 14-15; and added new claims 17-26.
Claims 1-2, 5-12, and 14-26 are currently pending and claims 1-2, 5-12, 14, and 17-22 are under consideration as claims 15-16 and 23-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 14, 2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/JP2019/048720 filed December 12, 2019, and claims priority under 119(a)-(d) to Japanese Application No. 2018-232144 filed on December 12, 2018.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Japanese Application No. 2018-232144, which papers have been placed of record in the file. Receipt of the certified English language translation of the Japanese priority document on October 16, 2025, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 16, 2025, is being considered by the examiner.
Sequence Compliance
Applicant is advised that the application is not in compliance with 37 CFR §§ 1.821-1.825.
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR §§ 1.821-1.825 for the reason(s) set forth below. Applicant must comply with the requirements of the sequence rules (37 CFR §§ 1.821- 1.825) in order to completely respond to this office action.
Specifically, the specification discloses many peptide sequences in chemical form, e.g., paragraphs [0373], Table 4 at [0389], Table 5 at [0391], Table 6 at [0392], Table 7 at [0394], Table 8 at [0395], Table 9 at [0397], etc., without sequence identifiers. Pursuant to MPEP 2422 and 37 CFR 1.821, any amino acid sequence with at least 4 defined amino acids (excluding branched sequences or sequences containing a D-amino acid) require a sequence identifier. MPEP 2422.01(III) states that if the applicant presents the sequence as a string of particular nucleotide bases or amino acids, whether by way of symbols, words or chemical structure, it is necessary to include the sequence in the "Sequence Listing" regardless of whether the applicant considers the sequence to be prior art, so long as the sequence meets the criteria of 37 CFR 1.821(a). In general, any sequence that is disclosed and/or claimed as a sequence, i.e., as a string of particular nucleotide bases or amino acids, and that otherwise meets the criteria of 37 CFR 1.821(a), must be set forth in the "Sequence Listing" (emphasis added). Thus, the amino acid sequences that contain at least 4 defined residues require a sequence identifier. In order to satisfy the sequence rules requirements, Applicant needs to provide an amendment to the instant claims and specification to include reference to the appropriate sequence identifier “SEQ ID NO:” in parenthesis next to each of the sequences having 4 or more amino acids. NOTE: not all paragraph citations provided above. Applicant’s assistance in ensuring all amino acid sequences having 4 or more than 4 defined amino acid residues have sequence identifiers and are included in the sequence listing.
In case of any new sequences not properly identified in the instant specification, Applicant is required to provide a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, a new or substitute paper copy of that “Sequence Listing”, an amendment directing the entry of that paper copy into the specification, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821(e) or 1.821(f) or 1.821(g) or 1.825(d). The instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (SEQ ID NO:) be made in the specification and claims wherever a reference is made to that sequence. For rules interpretation Applicant may call (571) 272-2533. See M.P.E.P. 2422.04.
Response to Arguments
Applicant's arguments filed 10/16/25 have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s argument that the subject matter of the instant application is irrelevant to the purposes of the sequence listing rules as it concerns chemically synthesized compounds that include a number of amino acids that are not found in any naturally occurring proteins or fragments thereof and are not synthesized in a biologic system (See Applicant’s Response received 10/16/25, pg. 28), it is found unpersuasive. Pursuant to MPEP 2421.02, “[t]he sequence rules embrace all unbranched nucleotide sequences with ten or more nucleotide bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 10 "specifically defined" nucleotides or 4 "specifically defined" nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not. All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database.” (emphasis added). Moreover, it is acknowledged that 37 CFR 1.821 states that amino acids are those L-amino acids commonly found in naturally occurring proteins and are listed in appendix C. However, 37 CFR 1.821 further states that “[a]ny amino acid sequence that contains post-translationally modified amino acids may be described as the amino acid sequence that is initially translated using the symbols shown in appendix C to this subpart, with the modified positions (e.g., hydroxylations or glycosylations) being described as set forth in appendix D to this subpart, but these modifications shall not be shown explicitly in the amino acid sequence. Any peptide or protein that can be expressed as a sequence using the symbols in appendix C to this subpart, in conjunction with a description in the Feature section, to describe, for example, modified linkages, cross links and end caps, non-peptidyl bonds, etc., is embraced by this definition.” Furthermore, it is noted that appendix C includes the symbol “Xaa”, which is utilized for residues that are unknown or “other”. More specifically, MPEP 2423 and 37 CFR 1.822(b) states that “each occurrence of a base or amino acid not appearing in appendices A and C, shall be listed in a given sequence as "n" or "Xaa," respectively, with further information, as appropriate, given in the Feature section, by including one or more feature keys listed in appendices E and F to this subpart.” As stated in the objection supra, the sequences that require a sequence identifier in the instant specification are those that do not contain a D-amino acid and/or are unbranched. For example, in Table 4, it is acknowledged that compound ID A01, A02, and A10 would not require a sequence identifier, but compounds A03-A09 would since each residue is an L-amino acid that is either natural or modified. Similar examination of the described sequences should be made. Thus, contrary to Applicant’s argument, the statutes are not limited to naturally occurring amino acids, but includes modified L-amino acids.
In response to Applicant’s argument that at least those sequences having D-amino acids or those of synthetic resins in nature are have been interpreted as not within the scope of the sequence listing rules (See Applicant’s Response received 10/16/25, pg. 29), it is found unpersuasive. As discussed supra, sequences containing a D-amino acid are excluded from the objection. As such, this response will focus on synthetic resins. Although it is acknowledged that the instant specification discusses synthesizing peptidic compounds, e.g., those listed in Table 4 in [0389], there is no indication that these peptidic compounds are synthetic resins. Notably, the peptide compounds encompass any peptidic compound as long as it is at least two amino acids where at least one of the amino acids has a structure depicted in claim 1. As such, although not expressly claimed, the scope of the claimed invention encompasses any peptidic compound. Furthermore, it is noted that a synthetic resin is defined as any synthetic organic compound consisting of a noncrystalline or viscous liquid substance (See Britannica Editors. "resin". Encyclopedia Britannica, 23 Jan. 2026, https://www.britannica.com/science/resin. Accessed 31 January 2026., at pg. 1, 1st paragraph). In modern industry natural resins have been almost entirely replaced by synthetic resins, which are divided into two classes, thermoplastic resins, which remain plastic after heat treatment, and thermosetting resins, which become insoluble and infusible on heating (See Britannica, pg. 1, last paragraph). Thus, the peptidic compounds as described in the instant specification do not constitute synthetic resins. As such, the fact that the peptidic compounds described in the instant specification are synthetically produced does not per se correlate to them being excluded from the sequence listing rules. Rather, the only peptidic compounds excluded are those that contain a D-amino acid. The peptidic compounds that do not contain a D-amino acid, but contain a non-natural L-amino acid are not expressly excluded. Therefore, contrary to Applicant’s argument, the chemically synthesized peptidic compounds in the specification are not interpreted as being akin to those having one or more D-amino acids (excluding those compounds that do) or those of synthetic resins.
Accordingly, the objection to the specification is maintained.
Response to Arguments
Applicant’s arguments, see Response, filed 10/16/25, with respect to the objection to the specification have been fully considered and are persuasive. The objection of the specification has been withdrawn.
Applicant’s arguments, see Response, filed 10/16/25, with respect to the 112(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-14 as being anticipated by Muraoka et al. WO2018/225864 A1 published on December 13, 2018 (cited in the IDS received on 6/9/21) (Please note: utilizing related US 2020/0131669 A1 (cited in the IDS received on 5/27/22) as the English language translation of ‘864) has been withdrawn.
Applicant’s arguments, see Response, filed 10/16/25, with respect to the 112(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-14 as being anticipated by Billich et al. Bioorg. Med. Chem. 13:3157-3167 (2005) has been withdrawn.
New Rejections Necessitated by Amendment
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1-2, 5-12, 14, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Billich et al. Bioorg. Med. Chem. 13:3157-3167 (2005) (cited in the Action mailed on 7/16/25).
For claims 1-2, 5-9, and 19-20, Billich et al. teaches novel cyclosporin derivatives that exhibit enhanced skin penetration properties including derivatives of 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA (cyclosporin A) (See Billich, abstract). The structure of 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA is:
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where R is hydrogen (See Billich, Scheme 1 and Table 2). Billich’s CsA derivative is 11 amino acids in length thereby constituting a specific embodiment within the amino acid ranges claimed in instant claims 5, 7, and 19-20. Billich’s CsA derivative is cyclic thereby satisfying the claim limitation as recited in instant claim 6. Billich’s CsA derivative contains 7 N-substituted amino acids thereby constituting greater than 30% of the proportion of the number of N-substituted amino acids to the total number of amino acids. As such, Billich’s CsA derivative contains a specific embodiment that that falls within the claimed ranges as recited in instant claims 8-9. Furthermore, Billich’s CsA derivative constitutes a peptide compound with two or more amino acids (i.e., 11 amino acids) connected where at least one of the amino acids (i.e., O-(2-hydroxyethyl)-D-Ser8) is capable of forming a hydrogen bond in a side chain as recited in instant claims 1-2.
Pursuant to MPEP 2144.09(I), [a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). In the instant case, the only difference between Bullich’s O-(2-hydroxyethyl)-D-Ser8 residue and
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(i.e., line 3, 2nd structure in claim 1) is an added methylene group between the ether and terminal hydroxyl group. However, an ordinary skilled artisan would expect the claimed amino acid and Bullich’s O-(2-hydroxyethyl)-D-Ser8 to have similar properties. When chemical compounds have “very close” structural similarities and similar utilities, without more a prima facie case may be made. In re Wilder, 563 F.2d 457 (CCPA 1977) (MPEP 2144.09.II). Stated alternatively, obviousness may be based solely upon structural similarity (an established structural relationship between a prior art compound and the claimed compound, as with homologs). See In re Duel, 51 F.3d 1552, 1559 (Fed. Cir. 1995). The necessary motivation to make the claimed compound (i.e., an added -CH2- between the ether and terminal hydroxyl group), and thus the prima facie case of obviousness, arises from the reasonable expectation that compounds similar in structure have similar properties. In re Gyurik, 596 F.2d 1012, 1018 (CCPA 1979). Therefore, the teachings of Billich suggest a peptide compound with two or more amino acids connected where at least one of the amino acids is
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as recited in instant claim 1.
For claim 2, although Billich et al. does not expressly teach that the O-(2-hydroxyethyl)-D-Ser8 residue is capable of forming a pseudo 4- to 7-membered ring in the side chain, since Billich et al. teaches the O-(2-hydroxyethyl)-D-Ser8 residue that is structurally and functionally similar to
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as recited in instant claim 1, the functional/structural property (i.e., capable of forming a pseudo 4- to 7-membered ring in the side chain) of the amino acid as claimed and the known amino acid are necessarily the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional/structural property (i.e., capable of forming a pseudo 4- to 7-membered ring in the side chain) which is necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Thus, the teachings of Billich et al. satisfies the claim limitation as recited in instant claim 2.
For claims 10-11, Billich et al. examine the skin permeability of 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA and derivatives thereof (See Billich, Table 2). However, Billich et al. does not identify the ClogP or Papp of the compounds. However, since Billich et al. teaches a specific peptide compound containing a O-(2-hydroxyethyl)-D-Ser8 residue that is structurally and functionally similar to
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as recited in instant claim 1, the functional properties (i.e., having a ClogP of 4.0 to 18 and a Papp of 1.0 x 10-7 cm/sec or higher) of the amino acid as claimed and the known amino acid are necessarily the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of new functional properties (i.e., having a ClogP of 4.0 to 18 and a Papp of 1.0 x 10-7 cm/sec or higher) which are necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Thus, the teachings of Billich et al. satisfies the claim limitations as recited in instant claims 10-11.
For claim 12, although Billich et al. does not expressly disclose a library of cyclic peptide compounds including 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA, since Billich et al. examined the skin permeability of 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA and 8 derivatives thereof as depicted in Table 2, such a grouping of cyclic peptides, one of which is 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA, would necessarily constitute a library comprising the peptide of claim 1. Thus, the teachings of Billich et al. satisfies the claim limitations as recited in instant claim 12.
For claim 14, as discussed supra for claim 1, the O-(2-hydroxyethyl)-D-Ser8 residue in Billich’s CsA derivative is structurally and functionally similar to
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as recited in instant claim 1. Thus, Billich’s O-(2-hydroxyethyl)-D-Ser8 residue contains an amino acid structure that is structurally and functionally similar to
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(i.e., line 3, 2nd structure) as recited in instant claim 14 for the same reasons stated supra for claim 1.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments with respect to claims 1-2, 5-12, 14, and 19-20 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. It is noted that the previous rejection over Billich was one of anticipation. That rejection has been overcome in light of Applicants’ amendments. However, a new ground of rejection is now applied as discussed supra.
Claims 1, 14, 17-18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Billich et al. Bioorg. Med. Chem. 13:3157-3167 (2005) (cited in the Action mailed on 7/16/25), as applied to claims 1 and 14 above, and further in view of Betts, et al., Bioinformatics for Geneticists, Barnes et al., eds., pg. 289-316 (2003), and Ahlbach et al., Future Med. Chem. 7:2121-2130 (2015), as applied to claims 17-18 and 21-22 herewith.
For claims 1 and 14, please see discussion of Billich et al. supra.
For claims 1, 14, 17-18, and 21-22, with respect to where the amino acid is
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:
As discussed supra, Billich et al. teaches novel cyclosporin derivatives that exhibit enhanced skin penetration properties including derivatives of 2-[O-(2-hydroxyethyl)-D-Ser8]-CsA (cyclosporin A) (See Billich, abstract). It is noted that 2-O-(2-hydroxyethyl)-D-Ser8 is identical to the amino acid structure:
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as recited in instant claims 1, 14, 17-18, and 21-22 except for an added methyl group in the side chain, i.e., Billich’s structure is O-(2-hydroxyethyl)-D-Ser compared to the instant residue of O-(2-hydroxypropyl)-D-Ser.
Betts et al. teaches that protein function is key to understanding of the consequences of amino acid substitution (See Betts, pg. 294, 3rd paragraph). Betts et al. discusses each of the 20 naturally occurring amino acids general preferences for substitutions and important specific details regarding their possible structure and functional roles (See Betts, pg. 299, last paragraph to pg. 300, 1st paragraph). In particular, Betts et al. teaches that serine can be substituted by other polar or small amino acids in particular threonine which differs only in that it has a methyl group in place of a hydrogen group found in serine (See Betts, pg. 307, 3rd paragraph). Both serine and threonine are fairly indifferent amino acids that can residue both within the interior of a protein or on the protein surface, and both are common in protein functional centers (See Betts, pg. 307, 4th- last paragraph). As such, two residues that only differ by an added methyl group exhibit similar structural and functional properties thereby constituting a conservative substitution. Although Billich’s residue is a serine derivative, the rationale suggested by Betts would apply given that the only structural difference between Billich’s serine derivative and the claimed serine derivative is a single methyl group as in the difference between serine and threonine.
Ahlbach et al. teaches that cyclosporin A (CSA) is a well-studied 11-residue cyclic peptide with seven N-methylated amino acids and it is passively permeable in both PAMPA and cell-based permeability assays (See Ahlbach, pg. 5, 2nd paragraph). Ahlbach et al. tested the passive permeabilities of CSA in addition to seven natural and synthetic CSA analogs with structural variants from the parent ranging from very conservative side chain substitutions (e.g., CSB: Abu2 [Wingdings font/0xE0]Ala2), to those with more dramatic backbone modifications (e.g., CSE: MeVal11 [Wingdings font/0xE0]Val11) (See Ahlbach, pg. 5, 2nd paragraph). CSA analogs with conservative substitutions adopt similar conformations in solution to that of the parent compound and had only small decreases in permeability relative to CSA (See Ahlbach, pg. 5, 3rd paragraph). It is noted that Ahlbach identifies the cyclosporin having a Abu2 [Wingdings font/0xE0]Ala2 substitution as a conservative substitution that exhibits similar structural and functional properties. As such, the removal of a methyl group (i.e., a methyl group removed from Abu to form Ala) did not significantly negate desired CSA structural and functional properties. Thus, when the teachings of Betts and Ahlbach are combined with those of Billich, an ordinary skilled artisan would be motivated with a reasonable expectation of success to modify Billich’s structure of O-(2-hydroxyethyl)-D-Ser such that a methyl group is added in the side chain to form Billich’s structure is O-(2-hydroxypropyl)-D-Ser.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the teachings of Billich and substitute O-(2-hydroxypropyl)-D-Ser8 in CSA instead of O-(2-hydroxyethyl)-D-Ser8 such that a methyl group is added to the Ser side chain at the carbon attached to the hydroxyl group where the modified CSA would exhibit similar structural properties such as the structural conformation in solution and functional properties such as passive membrane permeability. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because serine and threonine that are structurally distinguishable by a single methyl group in the side chain was known to be considered a conservative substitution exhibiting similar structural and functional properties as taught by Betts et al.; and because cyclosporin analogs that contain a conservative substitution in a side chain such as the removal of a methyl group relative to the CSA structure was known to exhibit similar structural properties such as the structural conformation in solution and functional properties such as passive membrane permeability as taught by Ahlbach et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the CSA analog of Billich et al. contained a O-(2-hydroxyethyl)-D-Ser8 substitution, and therefore, substituting O-(2-hydroxypropyl)-D-Ser8 in CSA instead of O-(2-hydroxyethyl)-D-Ser8 such that a methyl group is added to the Ser side chain at the carbon attached to the hydroxyl group would support the 2-[O-(2-hydroxypropyl)-D-Ser8]-CSA exhibiting similar structural properties such as the structural conformation in solution and functional properties such as passive membrane permeability relative to 2-[O-(2-hydroxyethyl)-D-Ser8]-CSA by constituting the simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Maintained/Modified in light of Applicants’ Amendments
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.
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Claims 1-2, 5-12, 14, and 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 7-8, 10-12, and 15-33 of copending Application No. 16/619,014 (Muraoka et al. US 2020/0131669 A1 (cited in the IDS received on 5/27/22)). Please note that the rejection has been updated in light of Applicants’ amendments. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘014 claims:
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(See ‘014 claims 1, 15, and 26). It is noted that the instant claimed peptide compound does not require a methythio group, a thiol group, an indole skeleton or a substituted or unsubstituted hydroxyphenyl group in a side chain of the cyclic portion thereby reading on ‘014 claim 15(1), and given that there is no limitations of the side chains of the amino acids in the instant peptide compounds other than one of the residues recited in claim 1 which is not required to be in a cyclic portion, the ‘014 claim 15(2)-(4) limitations are met. Regarding ‘014 claim 15(5), as depicted above, the side chain of an amino acid in the ‘014 peptide compound is identical to the side chain of the claimed amino acid of Ser(1-CF3-EtOH). As such, the ‘014 peptide compound anticipates the instantly claimed peptide compound and amino acid as recited in instant claims 1, 5-9, 14, and 17-22. Furthermore, the ‘014 claimed library containing the peptide compound constitutes the instantly claimed library as recited in instant claim 12.
The structural and/or functional properties recited in instant claims 1-2 and 10-11 are necessarily present in the ‘014 peptide compound. The structural and/or functional properties (i.e., capable of forming a hydrogen bond in a side chain, capable of forming a pseudo 4- to 7-membered ring in the side chain, having a ClogP of 4.0 to 18, and a Papp of 1.0 x 10-7 cm/sec or higher) of the amino acid/peptide compound as claimed and the known amino acid/peptide compound are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of new structural and/or functional properties (i.e., capable of forming a hydrogen bond in a side chain, capable of forming a pseudo 4- to 7-membered ring in the side chain, having a ClogP of 4.0 to 18, and a Papp of 1.0 x 10-7 cm/sec or higher) which are inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Thus, ‘014 claimed invention anticipates instant claims 1-2 and 10-11.
Therefore, the ‘014 claimed invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicants’ Arguments
Applicants respectfully request that the present double-patenting rejection be held in abeyance until otherwise allowable subject matter is found (See Applicants Response received on 10/16/25, pg. 31).
Response to Arguments
Applicant’s request to hold the present double-patenting rejection be held in abeyance until otherwise allowable subject matter is found is acknowledged. As such, the double-patenting rejection is maintained.
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 THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654