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 and 3-20 are pending. Claim 2 was canceled, claims 19-20 were added, and claims 1, 3, 10, and 18 were amended in the Reply filed 6/26/2026. Claims 3-8 and 11-17 are withdrawn. Claims 1, 9-10, and 18 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-10 and 18 as filed 1/23/2026) and the species of SEQ ID NO: 54 in the reply filed on 1/23/2026 was previously acknowledged.
The originally elected species was understood to be SEQ ID NO: 54, which has the following sequence:
Ile Ala Leu Ile Leu Glu Pro Xaa Cys Cys Gln Glu Arg Arg Ala
Or
IALILEPXCCQERRA
wherein Xaa or X, at position 8, is Sarcosine, and position 9 is a D-amino acid; wherein related species comprising SEQ ID NO: 54 in a pharmaceutical composition are understood to be obvious variants; but no specific carrier, diluent, or excipient was identified.
The originally elected species was understood to read upon previously pending claims 1-2, 9-10, and 18 (see, e.g., Reply filed 1/23/2026 at 5 at 3rd ¶). Claim 2 was canceled in the Reply filed 6/26/2026. The originally elected species is understood to read upon claims 1, 9-10, and 18 as filed 6/26/2026.
Following extensive search and examination, the originally elected species was deemed free of the prior art in the previous action (see, e.g., Action mailed 3/27/2026 at pages 2-4). Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, examination previously proceeded in the to the subgenus of species comprising the non-elected species of SEQ ID NO: 55, which was subsequently deemed obvious and/or anticipated by the prior art (see, e.g., Action mailed 3/27/2026 at pages 2-4, 12-16).
In the Response filed 6/26/2026, the claims were amended to exclude the non-elected species of SEQ ID NO: 55. Accordingly, per MPEP § 803.02(III)(A), examination has now been extended to the non-elected species of instant SEQ ID NOs: 12-24 and 42-53.
Following extensive search and examination, SEQ ID NOs: 12-24 and 42-53 have been deemed obvious in view of the prior art. Accordingly, claims 1, 9-10 and 18 are rejected in view of each non-elected species of instant SEQ ID NOs: 12-24 and 42-53.
Claims 11-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/23/2026.
Claims 3-8 and 19-20 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 1/23/2026.
Claims 1, 9-10, and 18 are presently considered
Denial of Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, US Provisional 63/108732 (filed 11/02/2020) fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163.
Lack of Express Support
Amended claim 1 is representative of the pending claim scope. Neither claim literally appears in Pro’732, and therefore the claims lack literal support in the Pro’732. More specifically, SEQ ID NOs: 54-55 do not literally appear in Pro’732.
Accordingly, Pro’732 fails to provide literal support for the pending claim scope that is synonymous or equivalent in scope.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163. In the absence of express support, the relevant issue is whether or not the claimed invention is supported by Pro’231 through implicit or inherent disclosures.
Upon review, zero inherent or implicit support commensurate in scope with the metes and bounds of the instant claims is found in Pro’732, at least because there is no implicit, inherent, or literal support for specifically arriving at the structures of instant SEQ ID NO: 54. According the claim language presently claimed is not supported by the provisional document by synonymous or equivalent language.
Accordingly, Pro’732 fails to provide implicit or inherent support for the pending claim scope that synonymous or equivalent in scope, or otherwise commensurate in scope with the pending claims.
Conclusion
Accordingly, priority to US Provisional 63/108732 (filed 11/02/2020) is denied for claim 1 and all of the dependents of those claims; these claims have been accorded a priority date of 11/01/2021, which corresponds to the filing date of PCT/US2021/057504 (filed 11/01/2021).
Information Disclosure Statement
No IDS was filed between the prior action and the Reply filed 6/26/2026.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope, and the sequences are generally understood as follows:
SEQ ID NOs: 6-7 and 25-26 are understood to be modified versions of PA-I8Sar further comprising a i+7 staple;
SEQ ID NOs:8-11 and 29-31 are understood to be modified versions of PA-I8Sar further comprising a i+4 staple;
SEQ ID NOs: 12-24 are understood to represent a D-amino acid scan of PA-I8Sar;
SEQ ID NOs: 35-38 are understood to represent PA-C9Sar further comprising a i+7 staple;
SEQ ID NOs: 39-41 are understood to represent PA-C9Sar further comprising a i+4 staple;
SEQ ID NOs: 42-53 are understood to represent a D-amino acid scan of PA-C9Sar;
SEQ ID NOs: 32-35 are PA-I8Sar variants comprising both a D-amino acid and a i+4 staple;
SEQ ID NOs: 27-28 appear to be variants of PA-I8Sar comprising a i+8 or i+3 staple, respectively; and
SEQ ID NO: 55 is identical to SEQ ID NO: 4 except position 15 of PA-I8Sar is deleted to form a 14-mer.
Additional claim interpretations are set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (see, e.g., MPEP § 2111.03(II)).
A “variant” is described in the Specification (see, e.g., Spec. filed 5/01/2023 at 21 at line 13 to line 26), and is understood to broadly include any type of modification without regard for functionality, including “fragments of the polypeptides” (i.e., single amino acids), fusion proteins, tagged proteins, etc. At this time, “variants” are optional components not present in the originally elected species, which have not been examined in view of the prior art.
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejection of claims 1, 9-10, and 18 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdraw in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US2016/0376322A1 is withdraw in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US10005818B2 (Jun. 26, 2018) is withdraw in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US2019/02096601 (published July 11, 2019; filed Jan. 9, 2018) is withdraw in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by WO2016/2103702 is withdraw in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-13 of U.S. Patent No. US10005818B2 (Jun. 26, 2018) is withdrawn in view of the amendments excluding SEQ ID NO: 55 as filed 6/26/2026. However, a new/revised rejection addressing the amended claim scope is set forth below.
The rejection of claims 1-2, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 17-19 of U.S. Patent No. 11135272 (Oct. 5, 2021) is withdrawn in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, and 7 of US Patent 10,933,116 (Mar. 2, 2021) is withdrawn in view of the amendments filed 6/26/2026. However, a new/revised rejection addressing the amended claim scope is set forth below.
The rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 9 of US Patent 10,947,279 (Mar. 16, 2021) is withdrawn in view of the amendments filed 6/26/2026.
The rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of US Patent 11,814,414 (Nov. 14, 2023; corresponding to US Application 17/169,758; US20210163543A1) is withdrawn in view of the amendments filed 6/26/2026. However, a new/revised rejection addressing the amended claim scope is set forth below.
The rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, and 10 of US Patent 12,297,235 (May 13, 2025; corresponding to US Application 18/480,170; US20240067680) is withdrawn in view of the amendments filed 6/26/2026. However, a new/revised rejection addressing the amended claim scope is set forth below.
The provisional rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. US18/035,846 (reference application; corresponding to US20230414506 A1) is withdrawn in view of the amendments filed 6/26/2026.
The provisional rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 2-18 of copending Application No. US18/288,274 (reference application; corresponding to US20240209036 A1) is withdrawn in view of the amendments filed 6/26/2026.
The provisional rejection of claims 1-2, 9-10, and 18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. US 19/182,023 (reference application) is withdrawn in view of the amendments filed 6/26/2026. However, a new/revised rejection addressing the amended claim scope is set forth below.
New or Revised Claim Rejections as Necessitated by Applicant 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 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.
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.
Claim 1, 9-10, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over US20160376322 in view of Simon et al.3
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection. The rejection addresses non-elected species of SEQ ID NOs: 12-24 and 42-53.
Regarding instant claims 1, 9-10, and 18, US’322 teaches, discloses, and claims pharmaceutical compositions comprising derivatives of Polar Assonant (PA) peptide (see, e.g., US’322 at ¶[0019]), which are disclosed for use in methods of treating and/or preventing hemolytic reactions, hypoxic ischemic encephalopathy, cystic fibrosis and other complement-related diseases and conditions, as well as for anti-microbial applications (see, e.g., US’322 at ¶[0019], claims 1-13). Regarding instant claim 1 and instant SEQ ID NOs: 12-24 and 42-53, US’322 explicitly teaches and discloses SEQ ID NO: 11 (“PA-I8Sar”, IALILEP(Sar)CCQERAA) and SEQ ID NO: 12 (“PA-C9Sar”, IALILEPI(Sar)CQERAA) (see, e.g., US’322 at Table 5 at ¶[0190]). These two sequences are among the top three tested compounds at Table 5 that are both soluble and exhibit low hemolysis (see id., noting that only seven species are soluble in water, and from among those seven PA-P7Sar, PA-I8Sar, and PA-C9Sar exhibit the lowest hemolysis).
US’322 differs from the instant claims and instant SEQ ID NOs: 12-24 and 42-53 as follows: SEQ ID NOs: 12-24 differ from the prior art compound of PA-I8Sar by the presence of a single D-amino acid at positions 1-2, 4-7, or 9-15, respectively. SEQ ID NOs: 42-53 differ from the prior art compound of PA-C9Sar by the presence of a single D-amino acid at positions 1-8, 11-13, or 15, respectively. Therefore, the relevant issue is whether or not it would have been obvious and routine to create D-amino acid variants of PA-I8Sar and/or PA-C9Sar in view of the prior art.
Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs), wherein a “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that some D-amino acid substitutions may be harmful by abolishing function or impacting folding (see, e.g., Simon at 12110 at col I-II), but that D-amino acid insertions can also desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed sequences of instant SEQ ID NOs: 12-24 and 42-53 are the obvious results of applying and using the known technique and methodology of Simon (i.e., a D-scan) to the known products of PA-I8Sar and PA-C9Sar of US’322, wherein such methodology would predictably yield 14 variants of each prior art peptide having a D-amino acid at a single position, which would desirably and predictably permit an artisan to identify critical stereocenters and positions amenable to D-amino acid substitutions, exactly as taught and suggested by Simon, wherein variants at positions amenable to D-amino acid substitutions would predictably and expectedly exhibit increased protease resistance and enhanced stability (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), and (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to modify a known polypeptide in a known manner according to a known methodology to obtain a known and expected result.
Accordingly, claims 1, 9-10, and 18 are rejected.
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.
[NSDP Rejection 01]
Claims 1, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-13 of U.S. Patent No. US10005818B2 (Jun. 26, 2018) in view of Simon et al.4 Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection.
Regarding instant claims 1, 9-10, and 18, US’818 claims synthetic peptides “comprising at least about 90% sequence identity” to PA-I8Sar (SEQ ID NO: 11; IALILEP(Sar)CCQERAA)5 and PA-C9Sar (SEQ ID NO: 12; IALILEPI(Sar)CQERAA)6, and therapeutic methods of using such sequences, which would necessarily require pharmaceutical compositions suitable for administration to subject (see, e.g., US’818 at claims 1-2, 5-13). The claimed phrase “synthetic peptide” and claimed differences (e.g., 10% sequence identity may be altered) are understood to amount to a single amino acid difference (e.g., 10% of a 15-mer is 1.5, which is only one amino acid difference as 0.5 amino acids is undefined) (see, e.g., US’818 at claims 1-2, 5-13); wherein such differences may include non-natural and non-proteinogenic amino acids (see, e.g., US’818 at col. 17 at lines 25-41, and col. 18 at lines 43-41; see, e.g., MPEP § 804(II)(B)(1), noting that it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim and to evaluate obvious variants of claimed subject matter).
The issued claims of the primary reference differ from the instant claims and instant SEQ ID NOs: 12-24 and 42-53 as follows: SEQ ID NOs: 12-24 differ from the prior art compound of PA-I8Sar by the presence of a single D-amino acid at positions 1-2, 4-7, or 9-15, respectively. SEQ ID NOs: 42-53 differ from the prior art compound of PA-C9Sar by the presence of a single D-amino acid at positions 1-8, 11-13, or 15, respectively. Therefore, the relevant issue is whether or not D-amino acid substitution variants of PA-I8Sar and/or PA-C9Sar, having the same exact base sequence as PA-I8Sar and PA-C9Sar, but comprising a single, D-amino acid substitution, is patentably distinct in view of the issued claims of the primary reference.
Such a difference was already known in the prior art, and was known to result from performing a routine “D-scan” of a peptide. Specifically, Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs), wherein a “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that although some D-amino acid substitutions may be harmful (see, e.g., Simon at 12110 at col I-II), that D-amino acid insertions can predictably, expectedly, and desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Applying the guidance of Simon to the claims of the primary reference, wherein PA-I8Sar and PA-C9Sar may include a single substitution (e.g., 10% identity difference), would yield instant SEQ ID NOs: 12-24 and 42-53, and such species literally fall within the scope of the issued patent.
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different D-amino acid substituted variants of the same common base sequences (e.g., PA-I8Sar and PA-C9Sar). Accordingly, the present claims are directed to obvious variants of the copending claims because an artisan would readily appreciate that other D-amino acid variants of the same exact base sequence (i.e., the ones instantly claimed) could predictably, routinely, and desirably be made via a D-scan methodology exactly as taught and suggested by Simon applied to the D-amino acid variants claimed by the primary reference, wherein the creation of such D-amino acid variants would predictably and expectedly identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions would predictably, expectedly, and desirably increase protease resistance and stability of the peptide (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), (G), 2144.09; see, e.g., MPEP § 804(II)(B)(3)(B)).
Accordingly, instant claims 1, 9-10, and 18 are rejected as not patentably distinct from the issued claims.
[NSDP Rejection 02]
Claims 1, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, and 7 of US Patent 10,933,116 (Mar. 2, 2021) in view of Simon et al.7 Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection.
Regarding instant claims 1, 9-10, and 18, US’116 claims methods utilizing synthetic peptides “comprising at least about 90% sequence identity” to PA-I8Sar (SEQ ID NO: 11; IALILEP(Sar)CCQERAA)8 and PA-C9Sar (SEQ ID NO: 12; IALILEPI(Sar)CQERAA)9, where the claimed therapeutic methods of using such sequences, which would necessarily require pharmaceutical compositions suitable for administration to subject (see, e.g., US’116 at claims 1, 3, 4, and 7). The claimed phrase “synthetic peptide” and claimed differences (e.g., 10% sequence identity may be altered) are understood to amount to a single amino acid difference (e.g., 10% of a 15-mer is 1.5, which is only one amino acid difference as 0.5 amino acids is undefined) (see, e.g., US’116 at claims 1, 3, 4, and 7); wherein such differences may include non-natural and non-proteinogenic amino acids (see, e.g., US’116 at col. 17 at lines 8-30, and col. 18 at lines 13-41; see, e.g., MPEP § 804(II)(B)(1), noting that it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim and to evaluate obvious variants of claimed subject matter).
The issued claims of the primary reference differ from the instant claims and instant SEQ ID NOs: 12-24 and 42-53 as follows: SEQ ID NOs: 12-24 differ from the prior art compound of PA-I8Sar by the presence of a single D-amino acid at positions 1-2, 4-7, or 9-15, respectively. SEQ ID NOs: 42-53 differ from the prior art compound of PA-C9Sar by the presence of a single D-amino acid at positions 1-8, 11-13, or 15, respectively. Therefore, the relevant issue is whether or not D-amino acid substitution variants of PA-I8Sar and/or PA-C9Sar, having the same exact base sequence as PA-I8Sar and PA-C9Sar, but comprising a single, D-amino acid substitution, is patentably distinct in view of the issued claims of the primary reference.
Such a difference was already known in the prior art, and was known to result from performing a routine “D-scan” of a peptide. Specifically, Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs), wherein a “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that although some D-amino acid substitutions may be harmful (see, e.g., Simon at 12110 at col I-II), that D-amino acid insertions can predictably, expectedly, and desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Applying the guidance of Simon to the claims of the primary reference, wherein PA-I8Sar and PA-C9Sar may include a single substitution (e.g., 10% identity difference), would yield instant SEQ ID NOs: 12-24 and 42-53, and such species literally fall within the scope of the issued claims.
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different D-amino acid substituted variants of the same common base sequences (e.g., PA-I8Sar and PA-C9Sar). Accordingly, the present claims are directed to obvious variants of the copending claims because an artisan would readily appreciate that other D-amino acid variants of the same exact base sequence (i.e., the ones instantly claimed) could predictably, routinely, and desirably be made via a D-scan methodology exactly as taught and suggested by Simon applied to the D-amino acid variants claimed by the primary reference, wherein the creation of such D-amino acid variants would predictably and expectedly identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions would predictably, expectedly, and desirably increase protease resistance and stability of the peptide (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), (G), 2144.09; see, e.g., MPEP § 804(II)(B)(3)(B)).
Accordingly, instant claims 1, 9-10, and 18 are rejected as not patentably distinct from the issued claims.
[NSDP Rejection 03]
Claims 1, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of US Patent 11,814,414 (Nov. 14, 2023; corresponding to US Application 17/169,758; US20210163543A1) in view of Simon et al.10. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection.
Regarding instant claims 1, 9-10, and 18, US’414 claims methods utilizing synthetic peptides “comprising at least 90% sequence identity” to PA-I8Sar (SEQ ID NO: 11; IALILEP(Sar)CCQERAA)11 and PA-C9Sar (SEQ ID NO: 12; IALILEPI(Sar)CQERAA)12, where the claimed therapeutic methods of using such sequences, which would necessarily require pharmaceutical compositions suitable for administration to subject (see, e.g., US’414 at claims 1-3 and 8). The claimed phrase “synthetic peptide” and claimed differences (e.g., 10% sequence identity may be altered) are understood to amount to a single amino acid difference (e.g., 10% of a 15-mer is 1.5, which is only one amino acid difference as 0.5 amino acids is undefined) (see, e.g., US’414 at claims 1-3 and 8); wherein such differences may include non-natural and non-proteinogenic amino acids (see, e.g., US’414 at col. 17 at lines 12-30, and col. 18 at lines 18-41; see, e.g., MPEP § 804(II)(B)(1), noting that it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim and to evaluate obvious variants of claimed subject matter).
The issued claims of the primary reference differ from the instant claims and instant SEQ ID NOs: 12-24 and 42-53 as follows: SEQ ID NOs: 12-24 differ from the prior art compound of PA-I8Sar by the presence of a single D-amino acid at positions 1-2, 4-7, or 9-15, respectively. SEQ ID NOs: 42-53 differ from the prior art compound of PA-C9Sar by the presence of a single D-amino acid at positions 1-8, 11-13, or 15, respectively. Therefore, the relevant issue is whether or not D-amino acid substitution variants of PA-I8Sar and/or PA-C9Sar, having the same exact base sequence as PA-I8Sar and PA-C9Sar, but comprising a single, D-amino acid substitution, is patentably distinct in view of the issued claims of the primary reference.
Such a difference was already known in the prior art, and was known to result from performing a routine “D-scan” of a peptide. Specifically, Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs), wherein a “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that although some D-amino acid substitutions may be harmful (see, e.g., Simon at 12110 at col I-II), that D-amino acid insertions can predictably, expectedly, and desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Applying the guidance of Simon to the claims of the primary reference, wherein PA-I8Sar and PA-C9Sar may include a single substitution (e.g., 10% identity difference), would yield instant SEQ ID NOs: 12-24 and 42-53, and such species literally fall within the scope of the issued claims.
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different D-amino acid substituted variants of the same common base sequences (e.g., PA-I8Sar and PA-C9Sar). Accordingly, the present claims are directed to obvious variants of the copending claims because an artisan would readily appreciate that other D-amino acid variants of the same exact base sequence (i.e., the ones instantly claimed) could predictably, routinely, and desirably be made via a D-scan methodology exactly as taught and suggested by Simon applied to the D-amino acid variants claimed by the primary reference, wherein the creation of such D-amino acid variants would predictably and expectedly identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions would predictably, expectedly, and desirably increase protease resistance and stability of the peptide (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), (G), 2144.09; see, e.g., MPEP § 804(II)(B)(3)(B)).
Accordingly, instant claims 1, 9-10, and 18 are rejected as not patentably distinct from the issued claims.
[NSDP Rejection 04]
Claims 1, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 and 5 of US Patent 12,297,235 (May 13, 2025; corresponding to US Application 18/480,170; US20240067680) in view of Simon et al.13. Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection.
Regarding instant claims 1, 9-10, and 18, US’235 claims methods utilizing synthetic peptides “comprising at least 90% sequence identity” to PA-I8Sar (SEQ ID NO: 11; IALILEP(Sar)CCQERAA)14 and PA-C9Sar (SEQ ID NO: 12; IALILEPI(Sar)CQERAA)15, where the claimed therapeutic methods of using such sequences, which would necessarily require pharmaceutical compositions suitable for administration to subject (see, e.g., US’235 at claims 1, 3, and 5). The claimed phrase “synthetic peptide” and claimed differences (e.g., 10% sequence identity may be altered) are understood to amount to a single amino acid difference (e.g., 10% of a 15-mer is 1.5, which is only one amino acid difference as 0.5 amino acids is undefined) (see, e.g., US’235 at claims 1, 3, and 5); wherein such the “90%” sequence identity is literally interpreted to include any single amino acid substitution at any position (see, e.g., US’235 at claims 1, 3, and 5).
The issued claims of the primary reference differ from the instant claims and instant SEQ ID NOs: 12-24 and 42-53 as follows: SEQ ID NOs: 12-24 differ from the prior art compound of PA-I8Sar by the presence of a single D-amino acid at positions 1-2, 4-7, or 9-15, respectively. SEQ ID NOs: 42-53 differ from the prior art compound of PA-C9Sar by the presence of a single D-amino acid at positions 1-8, 11-13, or 15, respectively. Therefore, the relevant issue is whether or not D-amino acid substitution variants of PA-I8Sar and/or PA-C9Sar, having the same exact base sequence as PA-I8Sar and PA-C9Sar, but comprising a single, D-amino acid substitution, is patentably distinct in view of the issued claims of the primary reference.
Such a difference was already known in the prior art, and was known to result from performing a routine “D-scan” of a peptide. Specifically, Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs), wherein a “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that although some D-amino acid substitutions may be harmful (see, e.g., Simon at 12110 at col I-II), that D-amino acid insertions can predictably, expectedly, and desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Applying the guidance of Simon to the claims of the primary reference, wherein PA-I8Sar and PA-C9Sar may include a single substitution (e.g., 10% identity difference), would yield instant SEQ ID NOs: 12-24 and 42-53, and such species literally fall within the scope of the issued claims.
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different D-amino acid substituted variants of the same common base sequences (e.g., PA-I8Sar and PA-C9Sar). Accordingly, the present claims are directed to obvious variants of the copending claims because an artisan would readily appreciate that other D-amino acid variants of the same exact base sequence (i.e., the ones instantly claimed) could predictably, routinely, and desirably be made via a D-scan methodology exactly as taught and suggested by Simon applied to the D-amino acid variants claimed by the primary reference, wherein the creation of such D-amino acid variants would predictably and expectedly identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions would predictably, expectedly, and desirably increase protease resistance and stability of the peptide (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), (G), 2144.09; see, e.g., MPEP § 804(II)(B)(3)(B)).
Accordingly, instant claims 1, 9-10, and 18 are rejected as not patentably distinct from the issued claims.
[Provisional NSDP Rejection 01]
Claim 1, 9-10, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/034,718 (reference application corresponding to US20230303623 A1) in view of Simon et al.16
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection.
Regarding instant claim 1-2, 9-10, and 18, the primary reference claims pharmaceutical formulations comprising related compounds that are highly similar to the claimed sequences (compare instant claims 1-2, 9-10, and 18 with copending claims 1-13 of App’718).
The scope of the copending claims differ as follows: Both copending claim sets are directed to derivatives and variants of PA-I8Sar (RLS-0088) and PA-C9Sar (RLS-0089) sequences, but the derivatives differ with respect to the exact placement of modifications relative to these base sequences (compare instant Spec. filed 5/01/2023 at Table 1, noting that the PA and RLS numbers are mostly consecutive, but then skip PA-0122 (RLS-0122)17, PA-0134 (RLS-0134)18, PA-0142 (RLS-0142)19, PA-0150 (RLS-0150)20, PA-0152 (RLS-0152)21, PA-0154 (RLS-0154)22, PA-0164 (RLS-0164)23, and PA-0168 (RLS-0168)24, which correspond to SEQ ID NOs: 6-13 as claimed by App’718).
Accordingly, the issue is whether or not the copending claims are patently distinct from one another under an obviousness rationale (see, e.g., MPEP § 804(II)(B)(2)-(3)).
Upon review of the pending claim scope and copending application, App’718 at SEQ ID NO: 12 (i.e., PA-0164, RLS-0164, IALILEPI(Sar)dCQERAA) and SEQ ID NO: 13 (i.e., PA-0168, RLS-0168, IALILEPI(Sar)CQERdAA) each share 100% sequence similarity to instant SEQ ID NOs: 42-53 (compare App’718 at SEQ ID NOs: 12-13 with instant SEQ ID NOs: 42-53, noting that all sequences are PA-C9Sar variants having a single residue substituted with a D-amino acid. Likewise, copending SEQ ID NO: 6 (IAdLILEP(Sar)CCQERAA, PA-0122, RLS-0122) shares 100% similarity to instant SEQ ID NOs: 12-24 (compare instant SEQ ID NOs: 12-24 with App’718 at SEQ ID NO: 6, showing 100% sequence similarity, noting that all sequences are PA-I8Sar variants having a single residue substituted with a D-amino acid).
Accordingly, the relevant issue is whether or not copending claims directed to D-amino acid substitution variants of the same exact base sequence, render other unclaimed D-amino acid substitutions of the same exact base sequence obvious or otherwise patentably indistinct.
Simon pertains D-amino acid substitutions in polypeptides, and Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs). A “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that some D-amino acid substitutions may be harmful by abolishing function or impacting folding (see, e.g., Simon at 12110 at col I-II), but that D-amino acid insertions can also desirably and predictably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different D-amino acid substituted variants of the same common base sequences (e.g., PA-I8Sar (RLS-0088) and PA-C9Sar (RLS-0089)). Accordingly, the present claims are directed to obvious variants of the copending claims because an artisan would readily appreciate that other D-amino acid variants of the same exact base sequence (i.e., the ones instantly claimed) could predictably, routinely, and desirably be made via a D-scan methodology exactly as taught and suggested by Simon applied to the D-amino acid variants claimed by the primary reference, wherein the creation of such D-amino acid variants would predictably and expectedly identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), (G), 2144.09; see, e.g., MPEP § 804(II)(B)(3)(B)).
Accordingly, instant claims 1, 9-10, and 18 are rejected.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
[Provisional NSDP Rejection 02]
Claims 1, 9-10, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. US 19/182,023 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been discussed in preceding rejections and in a separate section above, and those discussions are incorporated into the instant rejection.
Regarding instant claims 1, 9-10, and 18, The copending claims of App’023 claim synthetic peptides “comprising at least about 90% sequence identity” to PA-I8Sar (SEQ ID NO: 11; IALILEP(Sar)CCQERAA)25 and PA-C9Sar (SEQ ID NO: 12; IALILEPI(Sar)CQERAA)26, including pharmaceutical compositions (see, e.g., US’414 at claims 1-13). The claimed phrase “synthetic peptide” and claimed differences (e.g., 10% sequence identity may be altered) are understood to amount to a single amino acid difference (e.g., 10% of a 15-mer is 1.5, which is only one amino acid difference as 0.5 amino acids is undefined) (see, e.g., App’023 at claims 1-13); wherein such differences may include non-natural and non-proteinogenic amino acids (see, e.g., App’023 at Spec. filed 4/17/2025 at ¶¶[0101], [0106]; see, e.g., MPEP § 804(II)(B)(1), noting that it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim and to evaluate obvious variants of claimed subject matter), which would include D-amino acids.
The copending claims of the primary reference differ from the instant claims and instant SEQ ID NOs: 12-24 and 42-53 as follows: SEQ ID NOs: 12-24 differ from the prior art compound of PA-I8Sar by the presence of a single D-amino acid at positions 1-2, 4-7, or 9-15, respectively. SEQ ID NOs: 42-53 differ from the prior art compound of PA-C9Sar by the presence of a single D-amino acid at positions 1-8, 11-13, or 15, respectively. Therefore, the relevant issue is whether or not D-amino acid substitution variants of PA-I8Sar and/or PA-C9Sar, having the same exact base sequence as PA-I8Sar and PA-C9Sar, but comprising a single, D-amino acid substitution, are patentably distinct in view of the issued claims of the primary reference.
Such a difference was already known in the prior art, and was known to result from performing a routine “D-scan” of a peptide. Specifically, Simon explains that a “D-scan” was known and routine in the prior art at least circa 2016 (see, e.g., Simon at title, abs), wherein a “D-scan” is analogous to an alanine scan, but wherein D-amino acids are substituted at each position of a short polypeptide (see, e.g., Simon at title, abs, 12099 at col I-II at § Introduction, 12099-12100 at bridging ¶, 12100 at Fig. 1). The D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II). Simon explains that although some D-amino acid substitutions may be harmful (see, e.g., Simon at 12110 at col I-II), that D-amino acid insertions can predictably, expectedly, and desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, performing a “D-scan” by converting each amino acid within a short polypeptide into a D-amino acid, one at a time, is a known method having known benefits, which would be routine to perform in order to identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions, would predictably increase protease resistance and stability of the peptide.
Applying the guidance of Simon to the claims of the primary reference, wherein PA-I8Sar and PA-C9Sar may include a single substitution (e.g., 10% identity difference), would yield instant SEQ ID NOs: 12-24 and 42-53, and such species literally fall within the scope of the copending claims.
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different D-amino acid substituted variants of the same common base sequences (e.g., PA-I8Sar and PA-C9Sar). Accordingly, the present claims are directed to obvious variants of the copending claims because an artisan would readily appreciate that other D-amino acid variants of the same exact base sequence (i.e., the ones instantly claimed) could predictably, routinely, and desirably be made via a D-scan methodology exactly as taught and suggested by Simon applied to the D-amino acid variants claimed by the primary reference, wherein the creation of such D-amino acid variants would predictably and expectedly identify critical stereocenters and positions amenable to D-amino acid substitutions, wherein D-amino acid substitutions at positions amenable to such substitutions would predictably, expectedly, and desirably increase protease resistance and stability of the peptide (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), (G), 2144.09; see, e.g., MPEP § 804(II)(B)(3)(B)).
Accordingly, under an obviousness analysis, instant claims 1-2, 9-10, and 18 are not patentably distinct from the claim scope of App’023, because the copending Application recites and claims such structures, and such structures are obvious per Simon, and therefore such difference does not render the copending claims patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 6/26/2026 have been fully considered but they are not persuasive. Examiner notes that many arguments have been rendered moot; remaining applicable arguments are addressed below.
35 USC § 103
Applicant addresses the rejection under 35 USC 103 in view of US20160376322 in view of Simon at pages 6-7 (see, e.g., Reply filed 6/26/2026 at 6 at §VII to page 7 at 2nd full ¶), and those arguments are considered below.
Arguments alleging that a reference, considered alone, does not anticipate or render obvious the claimed invention: It is the Examiner’s understanding that Applicant alleges that “the ‘322 application does not teach, disclose, or suggest” the claimed invention when considered alone (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶; see also id. at 6-7 at bridging ¶, alleging that “’33 is completely silent”). In response to applicant's arguments against the references individually, 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). Here, the rejection is based upon US20160376322 in view of Simon, and not US’322 alone, and therefore such arguments are not persuasive.
Arguments addressing instant SEQ ID NO: 54 rather than SEQ ID NOs:12-24 and 42-53: It is the Examiner’s understanding that Applicant is alleging that SEQ ID NO: 54 is novel and has “different properties relative to SEQ ID NOs: 3-47”, and that SEQ ID NO: 54 “has many different properties relative to SEQ ID NO: 11 of the ‘322 application” (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶). Such arguments are neither disputed nor dispositive of the rejection because SEQ ID NO: 54 has already been identified as free of the prior art, and is not addressed or rejected in the rejection. Rather, the rejection addresses non-elected SEQ ID NOs: 12-24 and 42-53. Accordingly, all arguments pertaining to SEQ ID NO: 54 are moot and not persuasive regarding the allowability of instant SEQ ID NOs: 12-24 and 42-53, as no evidence that SEQ ID NO: 54 is representative of all other claimed sequences has been placed on record.
Allegations suggesting a lack of motivation: It is the Examiner’s understanding that Applicant is alleging that there is not motivation to arrive at the claimed invention (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶ to p. 7 at 1st partial ¶, alleging that an artisan “would not have any guidance or motivation”). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See 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), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the motivation and rationales relied upon by the Examiner to support a determination of obviousness have been explicitly recited in the rejection, and those rationales are MPEP §§ 2143(I)(B), (C), (D), (F), and (G). Applicant fails to address, acknowledge, or rebut any of these rationales with specificity, and therefore such express rationales supporting a determination of obviousness are not disputed with specificity on the instant record. If Applicant means to allege that the claimed products were arrived at for a different reason than relied upon by the Examiner, this is not persuasive because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)).
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶ to p. 7 at 1st partial ¶):
One of ordinary skill in the art, on reading the '322 application in combination with Simon, would not expect that modifying the peptide of SEQ ID NO: 11 to include a D-enantiomer at a specific residue would confer such properties.
(see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶).
[A] person of ordinary skill in the art would not have a reasonable expectation of success in modifying the peptides disclosed in the '322 application to incorporate D-enantiomeric amino acids, nor a reasonable expectation of success in doing so.
(see, e.g., Reply filed 6/26/2026 at 6-7 at bridging ¶).
This is not persuasive because these conclusory statements (i) do not reflect the proper legal standards for evaluating predictability, (ii) are unsupported by any objective evidence, and (iii) amount to a dismissal of the Simon reference. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Such statements amount to a complete dismissal of Simon and the reason a “D-scan” analysis was routine and known in the prior art. Specifically, Simon teaches that D-scans were known and that D-scan methodology provides known benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II), wherein D-amino acid insertions can also desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, D-scan methodologies, and the rationale for performing a “D-scan” analysis was already well-known in the art, and clearly identified on record in the rejection, wherein an artisan would have reasonably predicted and expected D-scan analysis to predictably yield D-amino acid substituted analogs of a prior art sequence, wherein such D-amino acid substituted analogs would be reasonably predicted and expected to enhance protein stability and increase resistance to proteases. Applicant provides zero evidence that SEQ ID NOs: 12-24 and 42-53 achieve more than what would be predicted and expected. Accordingly, arguments alleging lack of reasonable expectation of success and predictability have been fully considered but not found persuasive.
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶ to p. 7 at 1st partial ¶):
One of ordinary skill in the art, on reading the '322 application in combination with Simon, would not expect that modifying the peptide of SEQ ID NO: 11 to include a D-enantiomer at a specific residue would confer such properties.
(see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶).
[A] person of ordinary skill in the art would not have a reasonable expectation of success in modifying the peptides disclosed in the '322 application to incorporate D-enantiomeric amino acids, nor a reasonable expectation of success in doing so.
(see, e.g., Reply filed 6/26/2026 at 6-7 at bridging ¶).
If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art of both US’322 and Simon are presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding a prior art reference: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the prior art is not fully enabled or operable (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶ to p. 7 at 1st partial ¶, stating that there is not a “reasonable expectation of success” to incorporate D-enantiomeric amino acids into a known protein sequence). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that the prior art, including D-scans as taught by Simon, are fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Allegations suggesting improper or impermissible hindsight: It is the Examiner’s understanding that Applicant is suggesting that the Examiner’s position fails to establish a prima facie case of obviousness because the prior art does not lead an artisan to the instant invention (see, e.g., Reply filed 6/26/2026 at 6 to 7 at bridging ¶, alleging an artisan would have no guidance or motivation “save for impermissible hindsight”). If Applicant means to suggest that the Examiner arrived at the instantly claimed invention via the use of improper hindsight, this is not persuasive because any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant fails to identify a single aspect of the claimed invention that was not explicitly taught, disclosed, or suggested by the prior art relied upon by the Examiner, and merely performs anything other than its art-recognized function. Here, applying a known D-scan methodology to a known peptide predictably produces D-substituted variants of the peptide that would predictably and desirably exhibit improved protease resistance.
Allegations suggesting the references “teach away”: It is the Examiner’s understanding that Applicant is suggesting that the references “teach away” from the claimed invention in view of the statements alleging that “the ‘322 application does not teach, disclose, or suggest” the claimed invention when considered alone (see, e.g., Reply filed 6/26/2026 at 6 at 5th ¶; see also id. at 6-7 at bridging ¶, alleging that “’33 is completely silent”). Examiner notes that this argument is not persuasive because none of prior art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Applicant has not identified any disclosure that “criticizes, discredits, or otherwise discourages the solution claimed”. Accordingly, no “teaching away” has been identified on record.
No evidence of unexpected results or criticality of range has been placed on record: It is the Examiner’s understanding that Applicant is alleging that results with SEQ ID NO: 54 are “surprising and unexpected” (see, e.g., Reply filed 6/26/2026 at 6 to 7 at bridging ¶). First, SEQ ID NO: 54 is not the species under examination in the maintained rejection. Second, to date, zero evidence of unexpected results sufficient to rebut prima facie obviousness and commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 has been placed on record. No evidence showing criticality of range commensurate with the requirements of MPEP § 716.02(d) has been placed on record. Rather the instantly claimed species of SEQ ID NOs: 12-24 and 42-53 appear to merely yield the predicted and expected results; namely such sequences from applying to the known products of PA-I8Sar and PA-C9Sar of US’322 to a D-scan as taught by Simon, wherein the D-scan methodology would predictably yield 14 variants of each prior art peptide having a D-amino acid at a single position, which would desirably and predictably permit an artisan to identify critical stereocenters and positions amenable to D-amino acid substitutions, exactly as taught and suggested by Simon, wherein variants at positions amenable to D-amino acid substitutions would predictably and expectedly exhibit increased protease resistance and enhanced stability (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), and (G)). Critically, evidence confirming the expectations of the prior art actually weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
In sum, all proffered arguments have been fully considered but not found persuasive because such arguments appear to be a dismissal of Simon, and dismissal of the ordinary skill in the peptide arts, which included D-scans of therapeutic peptides, wherein such D-scans would predictably and expectedly yield D-amino acid substituted variants of known peptides expected and predicted to exhibit improved protease resistance.
Non-Statutory Double Patenting Rejections
Applicant addresses the NSDP rejections, jointly, at pages 7-8 (see, e.g., Reply filed 6/26/2026 at 7 at § VIII to page 8 at 4th full ¶). Examiner notes that such arguments are moot with respect to withdrawn rejections. Remaining applicable arguments applicable to the new/revised or maintained rejections are considered below.
Upon review, all applicable arguments to the new/revised and maintained rejections are understood to repeat arguments previously raised to address the 35 USC 103 rejection, which have been fully considered but not found persuasive for reasons set forth above (see, e.g., Reply filed 6/26/2026 at 8 at 4th full ¶; compare id. with Reply filed 6/26/2026 at 6 at 5th ¶ to p. 7 at 1st partial ¶). Such arguments have been fully considered but not found persuasive for reasons set forth above.
NSDP rejections address whether or not claimed subject matter is patentably distinct: Applicant appears to allege that the primary references do not “teach, disclose, or suggest” the claimed embodiments (see, e.g., Reply filed 6/26/2026 at 8 at 4th full ¶). This is neither disputed nor dispositive because NSDP rejections are based upon whether or not claimed subject matter is patentably distinct, which Applicant fails to dispute or address. Accordingly, the teachings, disclosure, and suggestions of the primary references are not at issue, per se, but rather the claimed subject matter and whether or not the claimed subject matter is patentably distinct relative to the instantly claimed subject matter. More specifically, the applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim would have been obvious over, the reference claims for the reasons set forth in the rejections above. In addition, arguments suggesting that an obviousness analysis is limited to explicit teachings is not persuasive because the Court has clearly explained that "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." (see KSR, 550 U.S. at 421, 82 USPQ2d at 1397), and that "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle" (see id. at 420, 82 USPQ2d at 1397). Accordingly, Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ" (see, e.g., id. at 418, 82 USPQ2d at 1396), which includes interpreting “90% sequence identity” to permit a single, desirable, routine, and well-known modification, such as that resulting from a routine D-scan, wherein such resulting sequences would be predicted and expected to desirably have improved protease resistance.
Arguments addressing instant SEQ ID NO: 54 rather than SEQ ID NOs:12-24 and 42-53: It is the Examiner’s understanding that Applicant is alleging that SEQ ID NO: 54 is novel and has “different properties relative to SEQ ID NOs: 3-47” (it is unknown what application or reference sequences are being referenced by Applicant), and that SEQ ID NO: 54 “has many different properties relative to SEQ ID NOs: 3-47” (again, it is unclear from what Application or reference “SEQ ID NOs: 3-47” originate) (see, e.g., Reply filed 6/26/2026 at 8 at 4th full ¶). Such arguments are neither disputed nor dispositive of the rejection because SEQ ID NO: 54 has already been identified as free of the prior art, and is not addressed or rejected in the rejection. Rather, the new/revised or maintained rejections at issue address the amended claim scope and non-elected species of SEQ ID NOs: 12-24 and 42-53. Accordingly, all arguments pertaining to SEQ ID NO: 54 are moot and not persuasive regarding the allowability of instant SEQ ID NOs: 12-24 and 42-53.
No evidence of unexpected results or criticality of range has been placed on record: It is the Examiner’s understanding that Applicant is alleging that results with SEQ ID NO: 54 are “surprising and unexpected” (see, e.g., Reply filed 6/26/2026 at 6 to 7 at bridging ¶, 8 at 4th full ¶). First, SEQ ID NO: 54 is not the species under examination in the maintained rejection. Second, to date, zero evidence of unexpected results sufficient to rebut prima facie obviousness and commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 has been placed on record.
Arguments premised upon ignoring or dismissing the teachings of a secondary reference: It is the Examiner’s understanding that Applicant alleges, generally, that the NSDP rejections are not proper because an artisan would allegedly
One of ordinary skill in the art, on reading these references, would not expect that modifying the disclosed peptides to include a D-enantiomer or staple at a specific residue would confer such properties. As these references are completely silent on incorporating D-enantiomeric forms of the amino acids, a person of ordinary skill in the art would not have a reasonable expectation of success in modifying the peptides disclosed in these references to incorporate D-enantiomeric amino acids, nor a reasonable expectation of success in doing so. Further, such a person would not expect to see the different properties of the D-enantiomeric substitution as discussed above.
(see, e.g., Reply filed 6/26/2026 at 8 at 4th full ¶).
These conclusory statements are unsupported by any objective evidence and fail to address or even acknowledge the teachings of Simon, which contradicts such conclusions. Here, such conclusions are directly contradicted by Simon because “D-scan” analysis was known and routine in the prior art, and provided known, expected, and predictable benefits, including the identification of critical stereocenters required for activity and identification of residues amenable to D-amino acid substitutions without abrogating functionality (see, e.g., Simon at title, abs, 12109 at col II at § Conclusion, 12110 at col I-II), wherein D-amino acid insertions would be predicted and expected to desirably stabilize proteins against proteolysis (see, e.g., Simon at 12099 at § Introduction; 12110 at col I-II). Accordingly, D-scan methodologies, and the rationale for performing a “D-scan” analysis was already well-known in the art, and clearly identified on record in the rejection, wherein an artisan would have reasonably predicted and expected D-scan analysis to predictably yield D-amino acid substituted analogs of a prior art sequence, wherein such D-amino acid substituted analogs would be reasonably predicted and expected to enhance protein stability and increase resistance to proteases. Applicant provides zero evidence that SEQ ID NOs: 12-24 and 42-53 achieve more than what would be predicted and expected. Accordingly, conclusory arguments amounting to a complete dismissal of the prior art of record, which fail to address the merits of the rejection, are not found persuasive.
Summary
In sum, all proffered and applicable arguments have been fully considered but not found persuasive because such arguments appear to be premised upon simply dismissing or ignoring the teachings of Simon and D-scan methodologies, and failing to address the combination of Simon and other references on the merits. Accordingly, the claims are rejected in view of the maintained and new/revised rejections set forth above. All new/revised rejections were necessitated by Applicant’s amendments.
Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 890684527 discloses a related sequence, namely PA (see, e.g., US’845 at claims and SEQ ID NO: 9).
US 942233728 discloses a related sequence, namely PA (see, e.g., id. at claims and SEQ ID NO: 9, noting that PA is IALILEPICCQERAA).
US 991475329 discloses a related sequence, namely PA (see, e.g., id. at claims and SEQ ID NO: 9, noting that PA is IALILEPICCQERAA).
US 1041479930 discloses a related sequence, namely PA (see, e.g., id. at claims and SEQ ID NO: 9, noting that PA is IALILEPICCQERAA).
US 1084409331 discloses a related sequence, namely PA (see, e.g., id. at claims and SEQ ID NO: 9, noting that PA is IALILEPICCQERAA).
US 1102046032 discloses and claims related methods and compounds, namely a PIC1 peptide comprising a PEGylated PA protein (see, e.g., US’460 at claims).
US 12257290 B233 discloses and claims related methods and compounds, namely a PIC1 peptide comprising a PEGylated PA protein (see, e.g., US’290 at claims).
US20230272012A134 (corresponding to instant Application 18/034,731) is the PG Publication corresponding to the instant Application.
US2024030904735 (corresponding to US App 18/657,556) pertains to related inventions based upon PA peptides (see, e.g., US’373 at title, abs, claims, SEQ ID NO: 9).
US2026002837336 (corresponding to US App 19/301,568) pertains to related inventions based upon PA peptides (see, e.g., US’373 at title, abs, claims, SEQ ID NO: 9).
Moiola et al.37 pertains to the general approach for improving peptide-based drugs by introducing a “staple” and creating a “stapled peptide”, which forces a short peptide to adopt an alpha helical structure (see, e.g., Moiola at title, abs, page 5-6 at § 2, page 5 at Scheme 1, page 6 at Fig. 3). Moiola explains that stapled peptides follow a pattern referred to as “i+4” and “i+7” (see, e.g., Moiola at page 6 at Fig. 3, 5-6 at § 2).
Bird et al.38 pertains to the general approach for improving peptide-based drugs by introducing a “staple” and creating a “stapled peptide”, which forces a short peptide to adopt an alpha helical structure, and is useful in therapeutic targeting of short peptides (see, e.g., Bird at title, abs, 2 at § “What can you do with stapled peptides?”). Bird identifies that the non-natural amino acids used to form “staples” were well known, and included R8 and S5, and that such non-natural amino acids formed staples following the positioning patterns of “i+4” and “i+7” (see, e.g., Bird at 3 at § “Strategic Planning”).
Bird et al.39 discusses pitfalls involved with stapled peptides and distinctions involving structural and cellular studies (see, e.g., Bird2014 at title, abs, passim). Bird2014 emphasizes that staples at particular positions may not be successful with respect to binding or functionality (see, e.g., Bird2014 at 831 at col I-II at bridging ¶), and emphasizes that staple location is a variable that is critical to consider and test (see, e.g., Bird2014 at 831 at col II at 1st full ¶, 833 at Fig. 1, Fig. 2 on 834, reproduced below):
PNG
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433
529
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Accordingly, when following known methodologies for creating stapled peptides, it is routine in the art to test different staple types (e.g., “i+4” and “i+7”) and different staple positions to find a fully functional, stapled peptide.
US10005818B2 (Jun. 26, 2018; cited in previous action) was previously applied under 35 USC 102 with respect to instant SEQ ID NO: 55, and is pertinent to the instant application (see, e.g., Action mailed 3/27/2026 at 13-14).
US2019/020966040 (published July 11, 2019; filed Jan. 9, 2018; cited in previous action) was previously applied under 35 USC 102 with respect to instant SEQ ID NO: 55, and is pertinent to the instant application (see, e.g., Action mailed 3/27/2026 at 14-15).
WO2016/21037041 was previously applied under 35 USC 102 with respect to instant SEQ ID NO: 55, and is pertinent to the instant application (see, e.g., Action mailed 3/27/2026 at 15-16).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new or revised 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 This is the PG Pub corresponding to subsequently issued US11135272, which was issued 10/05/2021.
2 Corresponds to issued US Patent 10,933,116, issued March 2, 2021.
3 Simon et al. D-Amino Acid Scan of Two Small Proteins, Journal of the American Chemical Society 2016 138 (37), 12099-12111, DOI: 10.1021/jacs.6b03765; hereafter “Simon”; cited in previous action.
4 Simon et al. D-Amino Acid Scan of Two Small Proteins, Journal of the American Chemical Society 2016 138 (37), 12099-12111, DOI: 10.1021/jacs.6b03765; hereafter “Simon”; cited in previous action.
5 Note that instant SEQ ID NOs: 12-24 are understood to represent a D-amino acid scan of PA-I8Sar.
6 Note that instant SEQ ID NOs: 42-53 are understood to represent a D-amino acid scan of PA-C9Sar
7 Simon et al. D-Amino Acid Scan of Two Small Proteins, Journal of the American Chemical Society 2016 138 (37), 12099-12111, DOI: 10.1021/jacs.6b03765; hereafter “Simon”; cited in previous action.
8 Note that instant SEQ ID NOs: 12-24 are understood to represent a D-amino acid scan of PA-I8Sar.
9 Note that instant SEQ ID NOs: 42-53 are understood to represent a D-amino acid scan of PA-C9Sar
10 Simon et al. D-Amino Acid Scan of Two Small Proteins, Journal of the American Chemical Society 2016 138 (37), 12099-12111, DOI: 10.1021/jacs.6b03765; hereafter “Simon”; cited in previous action.
11 Note that instant SEQ ID NOs: 12-24 are understood to represent a D-amino acid scan of PA-I8Sar.
12 Note that instant SEQ ID NOs: 42-53 are understood to represent a D-amino acid scan of PA-C9Sar
13 Simon et al. D-Amino Acid Scan of Two Small Proteins, Journal of the American Chemical Society 2016 138 (37), 12099-12111, DOI: 10.1021/jacs.6b03765; hereafter “Simon”; cited in previous action.
14 Note that instant SEQ ID NOs: 12-24 are understood to represent a D-amino acid scan of PA-I8Sar.
15 Note that instant SEQ ID NOs: 42-53 are understood to represent a D-amino acid scan of PA-C9Sar
16 Simon et al. D-Amino Acid Scan of Two Small Proteins, Journal of the American Chemical Society 2016 138 (37), 12099-12111, DOI: 10.1021/jacs.6b03765; hereafter “Simon”.
17 App’718 SEQ ID NO: 6 (i.e., PA-0122, RLS-0122, IAdLILEP(Sar)CCQERAA)
18 App’718 SEQ ID NO: 7 (i.e., PA-0134, RLS-0134, IAR8ILEP(Sar)CS5QERAA)
19 App’718 SEQ ID NO: 8 (i.e., PA-0142, RLS-0142, IAdLILEP(Sar)CS5QERS5A)
20 App’718 SEQ ID NO: 9 (i.e., PA-0150, RLS-0150, IALILER8I(Sar)CQERS5A)
21 App’718 SEQ ID NO: 10 (i.e., PA-0152, RLS-0152, IS5LILS5PI(Sar)CQERAA)
22 App’718 SEQ ID NO: 11 (i.e., PA-0154, RLS-0154, IALILES5I(Sar)CS5ERAA)
23 App’718 SEQ ID NO: 12 (i.e., PA-0164, RLS-0164, IALILEPI(Sar)dCQERAA)
24 App’718 SEQ ID NO: 13 (i.e., PA-0168, RLS-0168, IALILEPI(Sar)CQERdAA)
25 Note that instant SEQ ID NOs: 12-24 are understood to represent a D-amino acid scan of PA-I8Sar.
26 Note that instant SEQ ID NOs: 42-53 are understood to represent a D-amino acid scan of PA-C9Sar
27 Cited in previous action.
28 Cited in previous action.
29 Cited in previous action.
30 Cited in previous action.
31 Cited in previous action.
32 Cited in previous action.
33 Cited in previous action.
34 Cited in previous action.
35 Cited in previous action.
36 Cited in previous action.
37 Moiola et al., Stapled Peptides-A Useful Improvement for Peptide-Based Drugs. Molecules. 2019 Oct 10;24(20):3654. doi: 10.3390/molecules24203654. PMID: 31658723; PMCID: PMC6832507; hereafter “Moiola”; cited in previous action.
38 Bird et al., Chemical synthesis of hydrocarbon-stapled peptides for protein interaction research and therapeutic targeting. Curr Protoc Chem Biol. 2011 Sep 1;3(3):99-117, Author manuscript HHS Public Access; doi: 10.1002/9780470559277.ch110042. PMID: 23801563; PMCID: PMC4879976; hereafter “Bird”; cited in previous action.
39 Bird et al., Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chem Biol. 2014 Mar 21;9(3):831-7. doi: 10.1021/cb4003305. Epub 2014 Jan 3. PMID: 24358963; PMCID: PMC4131438; hereafter “Bird2014”; ; cited in previous action.
40 This is the PG Pub corresponding to subsequently issued US11135272, which was issued 10/05/2021.
41 Corresponds to issued US Patent 10,933,116, issued March 2, 2021.
