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 .
Election/Restrictions
In response to the restriction requirement dated 15 June 2026, Applicant elects, without
traverse: Group I drawn to a peptide comprising a teixobactin peptide. In response to a species election requirement, Applicant elects teixobactin prodrug A. The election reads on claims 1, 2, 4, 5, 8-11, 13, 14, 16-20. Applicant's election in the reply filed on 11 August 2026 is acknowledged.
Claims 1, 2, 4, 5, 8-11, 13, 14, 16-20, are hereby examined on the merits. Claim 12, 15, 21, 43 and 61 are withdrawn from further consideration pursuant to 37 CFR l.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Priority
This application filed 03/08/2024 is a National Stage entry of PCT/US2022/076130 , International Filing Date: 09/08/2022; PCT/US2022/076130 Claims Priority from Provisional Application 63364690 , filed 05/13/2022; PCT/US2022/076130 Claims Priority from Provisional Application 63241920 , filed 09/08/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/10/2026 complies with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the
examiner.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1, 2, 4, 5, 8-11, 13, 14, 16-20 are rejected under 35 U.S.C. 103 as being obvious over Hynjun Yang et al., hereinafter Yang (Hynjun Yang et al., Org Chem. 2020 February 07; 85(3): 1331–1339) in view of Han Liu et al., hereinafter Liu (Han Liu et al., Acc. Chem. Res. 2018, 51, 1643−1655).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Yang teaches teixobactin and teixobactin analogues (see Abstract).
Yang does not teach having one or more O-acyl isopeptide linkages between two amino acids in place of an amide bond.
Liu teaches that in the synthesis of cyclic peptide natural products e.g., teixobactin and analogues, intramolecular head-to-tail serine/threonine ligation (STL) is implemented on linear peptide C-terminal salicylaldehyde (SAL) ester precursors containing 4-10 amino acid residues with good efficiency and minimized oligomerization (see Abstract, last seven lines). Liu teaches that the high abundance of serine and threonine residues (12.7 %) in naturally occurring proteins and the good compatibility of STL with various C-terminal residues provide multiple choices for ligation sites.
Obviousness can 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. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Teixobactin, with O-acyl isopeptide linkages as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as intramolecular head-to-tail serine/threonine ligation as disclosed in Liu, provides an alternative tool for the chemical synthesis of homogenous proteins with site-specific and structure-defined modifications and cyclic peptide natural products. Thus, one would have recognized that applying the teaching of Yang to the method of Liu, would have yielded predictable results and improved the generation of teixobactin and its analogues (See MPEP § 2143 l(A)(D)).
Regarding claim 2, in addition to the obviousness rationale noted above, Liu teaches that N-terminal serine of one unprotected peptide carrying the 1, 2-hydroxylamine bifunctional group can undergo chemoselective oxazolidine formation with the aldehyde group of a salicylaldehyde (SAL) ester installed at the C-terminus of a second unprotected peptide as the reversible prior capture, and subsequent O-to-N acyl transfer affords an N,O-benzylidene acetal-linked peptide that upon acidolysis generates the natural peptidic Xaa−Ser/Thr linkage at the ligation site. Regarding the claim limitation ‘at physiological …chain’, absent evidence to the contrary, it is presumed that the teixobactin and disclosed in Liu and Yang, retains the activity as claimed. In this case, the limitation at issue, is the natural result of the structure, explicitly disclosed by the prior art " Id. at 1195-96, 112 USPQ2d at 1952. But see, Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (see MPEP §2112 .IV). Additionally, it is noted "the discovery of a previously unappreciated property of a prior art composition, or of 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 use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
Regarding claim 4, Liu teaches, intramolecular head-to-tail serine/threonine ligation (STL) (see Abstract).
Regarding claim 5, the rejection is noted above.
Regarding claim 8, Liu teaches, intramolecular head-to-tail serine/threonine ligation (STL) (see Abstract). Accordingly, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify serine at position 7 in Teixobactin, with O-acyl isopeptide linkages with the neighboring amino acid as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as intramolecular head-to-tail serine/threonine ligation is specifically disclosed in Liu. Thus, one would have recognized that applying the teaching of Yang to the method of Liu, would have yielded predictable results to generate teixobactin and its analogues with the recited modifications (See MPEP § 2143 l(A)(D)).
Regarding claim 9, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify serine at position 3 in Teixobactin, with O-acyl isopeptide linkages with the neighboring amino acid as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as intramolecular head-to-tail serine/threonine ligation is specifically disclosed in Liu. Thus, one would have recognized that applying the teaching of Yang to the method of Liu, would have yielded predictable results to generate teixobactin and its analogues with the recited modifications (See MPEP § 2143 l(A)(D)).
Regarding claim 10, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the serine residues at positions 3 and 7 in Teixobactin, with O-acyl isopeptide linkages with the neighboring amino acid as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as the method is specifically disclosed in Liu. Thus, one would have recognized that applying the teachings of Yang and Liu, would have yielded predictable results to generate teixobactin and its analogues with the recited modifications (See MPEP § 2143 l(A)(D)).
Regarding claim 11, Yang teaches allo-End at position 10. See below.
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Regarding claim 13, the structure in Yang is noted above -hydrophobic D-amino acid with an NH2 at position 1 (i.e. N-Me-D-Phe1).
Regarding claim 14, Yang teaches Ile at position 2.
Regarding claim 16, Yang teaches D-allo-Ile5 (i.e. D-hydrophobic amino acid).
Regarding claim 17, Yang teaches aza-D-Thr at residue position 8 (see Fig 3a).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Teixobactin comprising aza-D-Thr at residue position 8, with O-acyl isopeptide linkages as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as Yang teaches that replacement of the lactone ring oxygen with an NH group increases antibiotic activity, with D-aza-Thr8, Arg10-teixobactin (Fig 2a) exhibiting 2–8-fold greater antibiotic activity than Arg10-teixobactin (Fig 1a). Thus, one would have recognized that applying the teaching of Yang to the method of Liu, would have yielded predictable results and improved the generation of teixobactin and its analogues (See MPEP § 2143 l(A)(D)).
Regarding claim 18, Yang teaches macrolactam ring at residue positions 8 to 11. See rejection under claim 11.
Regarding claim 20, the structure of the elected species, prodrug A is identical to the structure disclosed in Yang.
Claims 1, 2, 4, 5, 8-11, 13, 14, 16-20 are rejected under 35 U.S.C. 103 as being obvious over Hynjun Yang et al., hereinafter Yang (Hynjun Yang et al., Org Chem. 2020 February 07; 85(3): 1331–1339) in view of Michael A. Morris et al., hereinafter Morris (Michael A. Morris et al., ACS Chem Biol. 2020 May 15; 15(5): 1222–1231) further in view of Han Liu et al., hereinafter Liu (Han Liu et al., Acc. Chem. Res. 2018, 51, 1643−1655).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The teachings of Liu and Yang have been set forth above.
Additionally, regarding claim 19, Morris teaches fluorescent teixobactin analogue. Morris teaches that fluorescent analogues of antibiotics provide valuable insights into the modes of action of antibiotics and antibiotic resistance and facilitate development of new antibiotics (see Introduction). Specifically Morris teaches Lys(Rhod)9,Arg10-teixobactin, labelling Lys9 with an amine-reactive rhodamine fluorophore (Abstract, line 7).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Teixobactin disclosed in Liu and Yang, with a fluorophore as disclosed in Morris. One motivated to do so would have a reasonable expectation of success, as Morris teaches that fluorescent antibiotic analogues enable tracking the drug and its interactions not only within bacterial cells but also within mammalian cells (see Introduction lines 1-3). Thus, one would have recognized that applying the teaching of Yang and Liu, to the method of Morris would have yielded predictable results and improved intracellular tracking of teixobactin and its analogues (See MPEP § 2143 l(A)(D)).
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.
Claims 1, 2, 4, 5, 8-11, 13, 14, 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11046730 in view of Hynjun Yang et al., hereinafter Yang (Hynjun Yang et al., Org Chem. 2020 February 07; 85(3): 1331–1339) in view of Michael A. Morris et al., hereinafter Morris (Michael A. Morris et al., ACS Chem Biol. 2020 May 15; 15(5): 1222–1231) further in view of Han Liu et al., hereinafter Liu (Han Liu et al., Acc. Chem. Res. 2018, 51, 1643−1655).
The teachings of Yang, Liu and Morris have been set forth above.
Regarding claim 1, reference patent teaches teixobactin (see claims 1-15).
Reference patent ‘730, does not teach O-acyl isopeptide linkages.
Obviousness can 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. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Teixobactin in reference patent ‘730, with O-acyl isopeptide linkages as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as intramolecular head-to-tail serine/threonine ligation as disclosed in Liu, provides an alternative tool for the chemical synthesis of homogenous proteins with site-specific and structure-defined modifications and cyclic peptide natural products. Thus, one would have recognized that applying the teaching of the reference patent ‘730 to the method of Liu, would have yielded predictable results and improved the generation of teixobactin and its analogues (See MPEP § 2143 l(A)(D)).
Regarding claim 2, in addition to the obviousness rationale noted above, Liu teaches that N-terminal serine of one unprotected peptide carrying the 1, 2-hydroxylamine bifunctional group can undergo chemoselective oxazolidine formation with the aldehyde group of a salicylaldehyde (SAL) ester installed at the C-terminus of a second unprotected peptide as the reversible prior capture, and subsequent O-to-N acyl transfer affords an N,O-benzylidene acetal-linked peptide that upon acidolysis generates the natural peptidic Xaa−Ser/Thr linkage at the ligation site.
Regarding claim 4, Liu teaches, intramolecular head-to-tail serine/threonine ligation (STL) (see Abstract).
Regarding claim 5, the rejection is noted above.
Regarding claim 8, Liu teaches, intramolecular head-to-tail serine/threonine ligation (STL) (see Abstract). Accordingly, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify serine at position 7 in Teixobactin, with O-acyl isopeptide linkages with the neighboring amino acid as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as intramolecular head-to-tail serine/threonine ligation is specifically disclosed in Liu. Thus, one would have recognized that applying the teaching of the reference patent ‘730, to the method of Liu, would have yielded predictable results to generate teixobactin and its analogues with the recited modifications (See MPEP § 2143 l(A)(D)).
Regarding claim 9, reference patent ‘730 does not teach O-acyl isopeptide linkage between serine at position 3 and the preceding amino acid.
Liu teaches O-acyl isopeptide linkage. Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify serine at position 3 in Teixobactin, with O-acyl isopeptide linkages with the neighboring amino acid as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as intramolecular head-to-tail serine/threonine ligation is specifically disclosed in Liu. Thus, one would have recognized that applying the teaching of the reference patent ‘730 to the method of Liu, would have yielded predictable results to generate teixobactin and its analogues with the recited modifications (See MPEP § 2143 l(A)(D)).
Regarding claim 10, reference patent ‘730 does not teach O-acyl isopeptide linkage between serine at position 3 and the preceding amino acid and serine at position 7 and the preceding amino acid.
Liu teaches O-acyl isopeptide linkage. Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the serine residues at positions 3 and 7 in Teixobactin, with O-acyl isopeptide linkages with the neighboring amino acid as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as the method is specifically disclosed in Liu. Thus, one would have recognized that applying the teachings of reference patent ‘730 and Liu, would have yielded predictable results to generate teixobactin and its analogues with the recited modifications (See MPEP § 2143 l(A)(D)).
Regarding claim 11, reference patent ‘730 teaches allo-End at position 10. See claim 2.
Regarding claim 13, reference patent ‘730 teaches -hydrophobic D-amino acid with an NH2 at position 1. See claim 4.
Regarding claim 14, reference patent ‘730 teaches Ile at position 2.
Regarding claim 16, reference patent ‘730 teaches D-allo-Ile5 (i.e. D-hydrophobic amino acid).
Regarding claim 17, reference patent ‘730 does not teach aza-D-Thr at residue position 8.
Yang teaches aza-D-Thr at residue position 8 (see Fig 3a).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Teixobactin comprising aza-D-Thr at residue position 8, with O-acyl isopeptide linkages as disclosed in Liu. One motivated to do so would have a reasonable expectation of success as Yang teaches that replacement of the lactone ring oxygen with an NH group increases antibiotic activity, with D-aza-Thr8, Arg10-teixobactin (Fig 2a) exhibiting 2–8-fold greater antibiotic activity than Arg10-teixobactin (Fig 1a). Thus, one would have recognized that applying the teaching of Yang and the reference patent ‘730, to the method of Liu, would have yielded predictable results and improved the generation of teixobactin and its analogues (See MPEP § 2143 l(A)(D)).
Regarding claim 18, reference patent ‘730 teaches macrolactam ring at residue positions 8 to 11. See claim 1, 11, 12, 15.
Regarding claim 19, reference patent does not teach fluorophore.
Morris teaches fluorescent teixobactin analogue. Morris teaches that fluorescent analogues of antibiotics provide valuable insights into the modes of action of antibiotics (see Introduction). Specifically Morris teaches Lys(Rhod)9,Arg10-teixobactin, labelling Lys9 with an amine-reactive rhodamine fluorophore (Abstract, line 7).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Teixobactin disclosed in the reference patent ‘730, Liu and Yang, with a fluorophore as disclosed in Morris. One motivated to do so would have a reasonable expectation of success, as Morris teaches that fluorescent antibiotic analogues enable tracking the drug and its interactions not only within bacterial cells but also within mammalian cells (see Introduction lines 1-3). Thus, one would have recognized that applying the teaching of the reference patent ‘730 and Liu, to the method of Morris, would have yielded predictable results and improved intracellular tracking of teixobactin and its analogues (See MPEP § 2143 l(A)(D)).
Regarding claim 20, the structure of the elected species, prodrug A is identical to the structure disclosed in reference patent ‘730 (see Fig 1).
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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/ARCHANA VARADARAJ/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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