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 .
This application is a domestic application, filed 29 Feb 2024.
Claims 1-19 are pending in the current application and are examined on the merits herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The specification at page 8, paragraph 23 includes an embedded hyperlink including the prefix “https://”.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a combination of natural phenomena without significantly more. The claims recite at claim 1 “An antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof, or comprising at least one polymyxin and at least one modified tunicamycin or salt thereof.” The alternative of “An antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof” is the combination of two products of nature. Claim 2 recites further limitations of the modified tunicamycin but does not require this alternative, and is interpreted to encompass the cited alternative. Claims 4-5 recite the combination with an additional antibiotic such as the β-lactam antibiotic is a penicillin, a cephalosporin, a monobactam, a carbapenem, or a combination thereof, where the alternative of penicillin is an additional product of nature.
Davis (WO 2018/224822 A1, published 13 Dec 2018, provided by Applicant in IDS filed 16 July 2025) discloses tunicamycin is a widely known and naturally occurring nucleoside antibiotic that has been demonstrated to exhibit antibacterial activity (page 1, lines 15-20).
Storm et al. (Ann. Rev. Biochem., 1977, 46, p723-763, cited in PTO-892) discloses polymyxins were first obtained from a strain of Bacillus polymyxa in 1947 (page 724, paragraph 2). The native antibiotics include polymyxin B and E (paragraph spanning page 725-726; page 726, figure 1).
Hutchings et al. (Current Opinion in Microbiology, 2019, 51, p72–80, cited in PTO-892) discloses penicillin is a natural product (page 73).
This judicial exception is not integrated into a practical application because these claims are directed the combination of the compounds themselves, each of which is a product of nature and each of which possesses the same biological or pharmacological functions or activities or chemical and physical properties in the combination as they do individually. While the application in Examples 1-3 at pages 17-20 of the specification describe a synergistic effect for the combination with a sub-MIC concentration of polymyxin B, the claimed invention is drawn to the combination of the compounds themselves in any amount or concentration.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not require more than the combination of the compounds themselves, each of which is a product of nature.
Therefore the alternative of “An antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof” and further comprising the β-lactam antibiotic penicillin, is directed to a combination of natural phenomena without significantly more.
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.
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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Price (US 10,513,533, issued 24 Dec 2019, provided by Applicant in IDS filed 07 Oct 2024).
Price teaches tunicamycin related compounds having an acyl chain double bond reduced and/or having an acyl chain double bond and an uracil ring double bond reduced, and the use of these tunicamycin related compounds to kill Gram-positive bacteria, treat Gram-positive bacterial diseases, and disinfect objects or surfaces (abstract). The tunicamycin related compounds are single reduced tunicamycins (Tun-R1) in which the fatty acid acyl 2′″,3′″-double bond is reduced and has the general structure of Formula 1, and double reduced tunicamycins (Tun-R2) in which the fatty acid acyl 2′″,3′″-double bond and the uracil 5,6-double bond are reduced and which has the general structure of Formula 2 (column 6, line 15 to column 7, line 60). Price teaches specific embodiments of Tun-R1 (figure 4A) and Tun-R2 (figure 4B), addressing limitations of claims 2. The tunicamycin related compounds can be combined with antibiotics that are not β-lactam antibiotics (referred to herein as “non-β-lactam antibiotic”), including but not limited to colistin (also known as polymyxin E) and polymyxin B (column 12, lines 5-30), addressing limitations of claim 1 and 3. Price teaches the working example of the tunicamycin related compounds combined with β-lactam antibiotics oxacillin, methicillin, and penicillin G (Example 7 at column 31, line 20 to column 32, line 20), addressing limitations of claims 4-5. The tunicamycin related compounds can be combined with any β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems (column 11, lines 50 to column 12, line 5).
Price does not specifically disclose the embodiment of the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof, or comprising at least one polymyxin and at least one modified tunicamycin or salt thereof (claim 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Price in order to select the combination of the tunicamycin related compound with colistin or polymyxin B and a β-lactam such as a pencillin. One of ordinary skill in the art would have been motivated to modify the teachings of Price with a reasonable expectation of success because Price teaches the tunicamycin related compound can be combined with antibiotics such as polymyxins and penicillins, and provides guidance of the working example of the tunicamycin related compounds combined with a pencillin, suggesting it would have been obvious to select the combination of antibiotics with a reasonable expectation of success.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Price (US 10,513,533, issued 24 Dec 2019, provided by Applicant in IDS filed 07 Oct 2024) in view of Davis (WO 2018/224822 A1, published 13 Dec 2018, provided by Applicant in IDS filed 16 July 2025), Vaara (Molecules, 2009, 24, article 249, 15 pages, provided by Applicant in IDS filed 16 July 2025), and Montagna et al. (Int. J. Environ. Res. Public Health, 2019, 16, 1895, 9 pages, cited in PTO-892).
Price teaches as above. Price further teaches a method of inhibiting or treating a bacterial infection caused by Gram-positive bacteria in an animal in need to treatment, said method comprising administering to said animal in need of treatment an effective amount of said antibacterial composition (claim 8 at column 33, lines 30-35; claim 18 at column 34, line 65 to column 35, line 5). Price further teaches the method of disinfecting a surface or object by applying at least one tunicamycin related compound, or a composition containing at least one tunicamycin related compound, to that surface or object to kill any Gram-positive bacteria that are present on the surface or object (column 15, lines 60-65).
Price does not specifically disclose the embodiment of the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof, or comprising at least one polymyxin and at least one modified tunicamycin or salt thereof (claim 1). Price does not specifically disclose the method of inhibiting or treating a bacterial infection caused by Gram-negative bacteria (claim 6). Price does not specifically disclose the method disinfecting a surface or object to kill any Gram-negative bacteria that are present on the surface or object (claim 11 and 16).
Davis teaches tunicamycin analogues which are useful in the prevention or treatment of bacterial infection (abstract). Davis teaches the antibacterial properties of tunicamycin derive from the transfer of a bacterially unique sugar-1-phosphoryl unit onto a bacteria specific lipid, catalyzed by the transmembrane enzyme Mra Y translocase. Mra Y exists in both Gram-positive and Gram-negative bacteria (page 1, lines 15-25). Davis teaches a lipid-altered tunicamycin analogue wherein the double bond of the fatty acid is reduced, such as compounds E2-E7 (page 11, line 5 to page 12, line 5; working examples at page 36, line 25 to page 43, line 30). The bacteria to be treated may be a Gram-positive bacteria or a Gram-negative bacteria (page 13, line 30 to page 14, line 25).
Vaara teaches polymyxins such as polymyxin B and polymyxin E are rapidly bactericidal against Gram-negative bacteria. Due to the global dissemination of extremely-drug resistant Gram-negative bacterial strains, polymyxins have resurged as the last-line drugs against those strains (abstract, page 1 of 15).
Montagna et al. teaches nosocomial infections cause significant morbidity and mortality worldwide, and the pathogenic organisms responsible for such infections can develop resistance to antimicrobial agents. The development of disinfection procedures that are effective against all microorganisms is essential for limiting the spread of nosocomial infections (page 1, abstract). A total of 187 bacteria for texting were isolated from recovered hospitalized patients, and include both Gram-positive and Gram-negative bacteria (page 2, paragraph 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Price in view of Davis, Vaara, and Montagna et al. in order to select the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or modified tunicamycin or salt thereof, and to treat a subject or surface for Gram-negative bacteria in addition to Gram-positive bacteria. One of ordinary skill in the art would have been motivated to combine Price in view of Davis, Vaara, and Montagna et al. with a reasonable expectation of success because Price teaches the tunicamycin related compound can be combined with antibiotics such as polymyxins and penicillins, provides guidance of the working example of the tunicamycin related compounds combined with a pencillin suggesting it would have been obvious to select the combination of antibiotics with a reasonable expectation of success, and teaches methods of treating a subject or surface for Gram-positive bacteria; Davis teaches tunicamycins are known to have activity against both Gram-positive and Gram-negative bacteria and suggests treatment of Gram-positive or Gram-negative bacteria is desired; and Vaara teaches polymyxins are known to be bactericidal against Gram-negative bacteria. Therefore it would have been obvious to modify the treatment of Price in order to treat a subject or surface for Gram-negative bacteria because Davis teaches tunicamycins are known to have activity against both Gram-positive and Gram-negative bacteria and provides a reasonable expectation of success to treat Gram-negative bacteria in addition to Gram-positive bacteria. Vaara provides additional guidance to select specifically the combination of the tunicamycin related compound with a polymyxin because Vaara teaches polymyxins are known to be rapidly bactericidal against Gram-negative bacteria. Montagna et al. provides additional guidance that one of ordinary skill in the art would have been motivated to treat a subject or surface for Gram-negative bacteria in addition to Gram-positive bacteria because Montagna et al. teaches nosocomial bacteria found on hospital surfaces or patients include both Gram-negative bacteria and Gram-positive bacteria.
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 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 15-16 of U.S. Patent No. 10,513,533 (reference patent) in view of Price (US 10,513,533, issued 24 Dec 2019, provided by Applicant in IDS filed 07 Oct 2024).
Reference claims 1-4 and 15-16 of the reference patent are drawn to an antibacterial composition comprising tunicamycin related compound and an antibiotic, wherein said antibiotic is a β-lactam antibiotic, or a combination of a β-lactam antibiotic and a non-β-lactam antibiotic, where the tunicamycin related compound corresponds to claimed formula I where R2 is Y. Reference claims 4 and 16 recite the β-lactam antibiotic is selected from the group consisting of a penicillin, a cephalosporin, a monobactam, a carbapenem, and a combination thereof, corresponding to limitations of claim 5.
Reference claims 1-4 and 15-16 do not specifically disclose the embodiment of the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof, or comprising at least one polymyxin and at least one modified tunicamycin or salt thereof (claim 1).
Price qualifies as prior art under 35 USC 102(a)(1) and teaches as above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Reference claims 1-4 and 15-16 in view of Price in order to select from within the scope of the Reference claims the combination of the tunicamycin related compound with colistin or polymyxin B and a β-lactam such as a pencillin. One of ordinary skill in the art would have been motivated to combine Reference claims 1-4 and 15-16 in view of Price with a reasonable expectation of success because Price teaches the invention of the Reference claims are a tunicamycin related compound that can be combined with antibiotics such as polymyxins and penicillins, and the Reference claims encompass the combination of the tunicamycin related compound a combination of a β-lactam antibiotic and a non-β-lactam antibiotic, suggesting it would have been obvious to select the combination of antibiotics with a reasonable expectation of success.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 15-19 of U.S. Patent No. 10,513,533 (reference patent) in view of Price (US 10,513,533, issued 24 Dec 2019, provided by Applicant in IDS filed 07 Oct 2024) in view of Davis (WO 2018/224822 A1, published 13 Dec 2018, provided by Applicant in IDS filed 16 July 2025), Vaara (Molecules, 2009, 24, article 249, 15 pages, provided by Applicant in IDS filed 16 July 2025), and Montagna et al. (Int. J. Environ. Res. Public Health, 2019, 16, 1895, 9 pages, cited in PTO-892).
Reference claims 1-4 and 15-16 of the reference patent are drawn to an antibacterial composition comprising tunicamycin related compound and an antibiotic, wherein said antibiotic is a β-lactam antibiotic, or a combination of a β-lactam antibiotic and a non-β-lactam antibiotic, where the tunicamycin related compound corresponds to claimed formula I where R2 is Y of claim 2. Reference claims 4 and 16 recite the β-lactam antibiotic is selected from the group consisting of a penicillin, a cephalosporin, a monobactam, a carbapenem, and a combination thereof, corresponding to limitations of claim 5. Reference claims 5-11 and 17-19 are drawn to a method of killing Gram-positive bacteria in or on an animal, a method of inhibiting or treating a bacterial infection caused by Gram-positive bacteria in an animal in need to treatment, or a method of disinfecting an object or a surface that has Gram-positive bacteria on said object or said surface comprising applying an effective amount of said tunicamycin related compound to said object or said surface in order to kill said Gram-positive bacteria present on said object or said surface.
Reference claims 1-11 and 15-19 do not specifically recite the embodiment of the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof, or comprising at least one polymyxin and at least one modified tunicamycin or salt thereof (claim 1). Reference claims 1-11 and 15-19 do not specifically recite the method of inhibiting or treating a bacterial infection caused by Gram-negative bacteria (claim 6). Reference claims 1-11 and 15-19 do not specifically recite the method disinfecting a surface or object to kill any Gram-negative bacteria that are present on the surface or object (claim 11 and 16).
Price qualifies as prior art under 35 USC 102(a)(1) and teaches as above.
Davis teaches as above.
Vaara teaches as above.
Montagna et al. teaches as above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the Reference claims in view of Price, Davis, Vaara, and Montagna et al. in order to select the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or modified tunicamycin or salt thereof, and to treat a subject or surface for Gram-negative bacteria in addition to Gram-positive bacteria. One of ordinary skill in the art would have been motivated to combine the Reference claims in view of Price, Davis, Vaara, and Montagna et al. with a reasonable expectation of success for the same reasoning explained above regarding Price in view of Davis, Vaara, and Montagna et al.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-10 of U.S. Patent No. 12,245,589 (reference patent) in view of Price (US 10,513,533, issued 24 Dec 2019, provided by Applicant in IDS filed 07 Oct 2024) in view of Davis (WO 2018/224822 A1, published 13 Dec 2018, provided by Applicant in IDS filed 16 July 2025), Vaara (Molecules, 2009, 24, article 249, 15 pages, provided by Applicant in IDS filed 16 July 2025), and Montagna et al. (Int. J. Environ. Res. Public Health, 2019, 16, 1895, 9 pages, cited in PTO-892).
Reference claims 1-6 and 8-10 of the reference patent are drawn to an antibacterial composition comprising tunicamycin related compound and an antibiotic, wherein said antibiotic is a β-lactam antibiotic, or a combination of a β-lactam antibiotic and a non-β-lactam antibiotic, where the tunicamycin related compound corresponds to claimed formula II that is double-reduced of claim 2. Reference claim 3 further comprising an antibiotic, wherein said antibiotic is a β-lactam antibiotic, a non-β-lactam antibiotic, or combination thereof, corresponding to limitations of claim 4. Reference claims 4-6 are drawn to a method of killing Gram-positive bacteria in or on an animal, a method of inhibiting or treating a bacterial infection caused by Gram-positive bacteria in an animal in need to treatment, or a method of disinfecting an object or a surface that has Gram-positive bacteria on said object or said surface comprising applying an effective amount of said tunicamycin related compound to said object or said surface in order to kill said Gram-positive bacteria present on said object or said surface.
Reference claims 1-6 and 8-10 do not specifically recite the embodiment of the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or salt thereof, or comprising at least one polymyxin and at least one modified tunicamycin or salt thereof (claim 1). Reference claims 1-6 and 8-10 do not specifically recite the method of inhibiting or treating a bacterial infection caused by Gram-negative bacteria (claim 6). Reference claims 1-6 and 8-10 do not specifically recite the method disinfecting a surface or object to kill any Gram-negative bacteria that are present on the surface or object (claim 11 and 16).
Price qualifies as prior art under 35 USC 102(a)(1) and teaches as above.
Davis teaches as above.
Vaara teaches as above.
Montagna et al. teaches as above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the Reference claims in view of Price, Davis, Vaara, and Montagna et al. in order to select the antibacterial composition comprising at least one antibacterial composition comprising at least one polymyxin and at least one tunicamycin or modified tunicamycin or salt thereof, and to treat a subject or surface for Gram-negative bacteria in addition to Gram-positive bacteria. One of ordinary skill in the art would have been motivated to combine the Reference claims in view of Price, Davis, Vaara, and Montagna et al. with a reasonable expectation of success for the same reasoning explained above regarding Price in view of Davis, Vaara, and Montagna et al.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan S Lau whose telephone number is (571)270-3531. The examiner can normally be reached Monday-Friday 9a-5p Eastern.
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, Scarlett Goon can be reached at (571)270-5241. 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.
/JONATHAN S LAU/ Primary Examiner, Art Unit 1693
Prosecution Insights