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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission dated 03/26/2026 has been entered pursuant to RCE filed on 03/26/2026.
Pursuant to the amendment dated 03/23/2026, claims 2, 3, 8, 13-17 and 19 are cancelled and claims 1, 4-7, 18 and 30 are amended. Claims 1, 4-7, 9-12, 18, and 20-31 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/GB2020/052525 filed on 10/09/2020 and claims foreign priority to United Kingdom 1914847.7 filed on 10/14/2019.
Withdrawn Rejections
Applicant’s amendment, filed on 03/26/2026, with respect to the rejection of claims 1-4, 6-7 and 9-12 under 35 U.S.C. 103 as being unpatentable over Coates et al. (WO 2018/162928 Al, published 09/13/2018, see PTO-892) has been fully considered and is persuasive. Applicant has amended claim 1 to add the additional limitation where in the combination of zidovudine and a tetracycline antibiotic is synergistic in treating bacterial infections which is not taught by Coates. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 03/26/2026, with respect to the rejection of claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Coates et al. (WO 2018/162928 Al, published 09/13/2018, see PTO-892) as applied to claim 1 above, and further in view of Brogden (Evaluations on New Drugs, published 11/03/2012, see PTO-892) has been fully considered and is persuasive. Applicant has amended claim 1 to add the additional limitation where in the combination of zidovudine and a tetracycline antibiotic is synergistic in treating bacterial infections which is not taught by Coates. The rejection is hereby withdrawn.
New Rejections and Maintained rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-7and 9-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim1 is drawn to a method of treating a bacterial infection, the method comprising administering to a subject a combination comprising zidovudine or a pharmaceutically acceptable derivative thereof and a tetracycline antibiotic selected from tetracycline, chlortetracycline, oxytetracycline, demeclocycline, lymecycline, meclocycline, methacycline, minocycline, rolitetracycline, and doxycycline, or a pharmaceutically acceptable derivative or prodrug thereof, wherein the combination is synergistic in treating bacterial infections.
The instant disclosure, however, does not describe a representative number of species of the claimed genus for either the tetracycline or the bacteria showing a synergistic relationship between the tetracycline and zidovudine nor does the disclosure identify a structure-function relationship that could be used to predictably identify which of the claimed tetracyclines would work synergistically in combination with zidovudine and against which bacterial strains.
The instant specification (pages 23-25) discloses the in vitro synergistic effect of zidovudine and doxycycline in combination against five bacterial strains (BAA2469 NDM-1 Escherichia coli, BAA2470 NDM-1 Klebsiella pneumoniae, BAA2471 NDM-1 Escherichia coli, BAA2472 NDM-1 Klebsiella pneumoniae, and NCTC13443 NDM-1 Klebsiella pneumoniae). However, there are no examples of the other tetracyclines in combination with zidovudine to show the synergistic antibacterial effect against any bacterial listed in instant claim 1.
Brochado et al. (Nature, published 07/04/2018, see PTO-892) is drawn to the study of species-specific activity of antibacterial drug combinations. Brochado profiled almost 3,000 dose-resolved combinations of antibiotics, human-targeted drugs and food additives in six strains from three Gram-negative pathogens—Escherichia coli, Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa—to identify general principles for antibacterial drug combinations and understand their potential (abstract). Brochado investigated three tetracyclines including doxycycline, minocycline, and tigecycline in combination with a second drug (Supplemental Table 2). In comparing doxycycline and minocycline when combined with loperamide, doxycycline plus loperamide showed a synergistic effect against E. coli BW25113, E. coli iAi1, and P. aeruginosa PA14. However, the combination of minocycline and loperamide only showed a synergistic effect against E. coli BW25113. The results support that synergy in one tetracycline does not indicate the likelihood of synergy in another tetracycline. Further, the results show that even against the same genus of bacteria, the synergistic effect was unpredictable across the strains.
Therefore, the state of the art prior to the effective filing date of the claimed invention demonstrates that synergy across even the same class of antibiotics such as tetracyclines is unpredictable.
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.
Claims 18, and 20-28 are rejected under 35 U.S.C. 103 as being unpatentable over Coates et al. (WO 2018/162928 Al, published 09/13/2018, see PTO-892).
Coates is drawn to a method for restoring efficacy of an antibacterial agent (title). The method is for restoring the efficacy or prolonging the life of an antibacterial agent by combining the antibacterial agent with at least two antibiotic resistance breakers, wherein each antibiotic resistance breaker is used independently with the antibacterial agent so as to at least partially restore the efficacy thereof (page 1, lines 3-6). Coates teaches that the antibacterial activity of the antibacterial agent and the antibiotic resistance breaker is additive or synergistic and the antibacterial activity is against a drug-resistance Gram-negative bacterium such as E. coli or K. pneumoniae (page 7, lines 26-30) and other infections due to organisms from Enterobacteriaceae (page 24, lines 5-28). The antibiotic resistance breaker may be a repurposed existing drug and may be zidovudine (page 9, lines 1-9). The antibacterial agents may be tetracyclines, such as tetracycline, demeclocycline, doxycycline, lymecycline, minocycline, oxytetracycline, chlortetracycline, meclocycline and methacycline, as well as glycylcyclines (e.g. tigecycline) (page 12, lines 31-33). The compounds used are preferably provided in the form of pharmaceutical compositions or formulations and may be used either as separate formulations or as a single combined formulation. The antibacterial agent and antibiotic resistance breakers may be combined in the same formulation and in a formulation suitable for oral, parenteral, rectal, or topical administration (page 29, lines 18-29).
Coates does not exemplify a composition or administration of a composition comprising zidovudine and a tetracycline.
It would have been prima facie obvious before the effective filing date of the claimed invention to combine both zidovudine and a tetracycline in a composition and use the composition for treatment of a microbial infection to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to combine zidovudine and a tetracycline in a composition for treatment of a microbial infection because Coates teaches that an antibacterial such as tetracycline and an antibiotic resistance breaker such as zidovudine can work additively or synergistically against drug-resistance Gram-negative bacterium and infections due to organisms from Enterobacteriaceae. One of ordinary skill in the art would have a reasonable expectation of success because Coates teaches a composition comprising antibacterials such as tetracycline and antibiotic resistance breakers such as zidovudine in a composition for the treatment of infections.
It is noted that the prior art does not teach that the combination of zidovudine and the tetracycline antibiotic is synergistic in treating bacterial infections. However, the cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since the composition would be capable of performing the intended use. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Claims 18 and 20-28 rejected under 35 U.S.C. 103 as being unpatentable over Bonner et al. (US 2006/0172956 A1, published 08/03/2006, see PTO-892).
Bonner is drawn to compositions, combinations of medicaments, and methods for the treatment of certain conditions such as arthritis, and in particular, reactive arthritis, osteoarthritis, and bursitis, among others (abstract). Arthritis is an inflammatory condition (paragraph 0013). Bonner teaches a pharmaceutical composition effective in the treatment of conditions such as reactive arthritis, the composition comprising a combination of an antiviral compound and a broad-spectrum antibiotic (paragraph 0016-0017). Bonner teaches that the antiviral compound is a nucleoside analogue such as zidovudine (paragraph 0022). The broad-spectrum antibiotic compound for use in the invention may be a tetracycline and may preferably be tetracycline, chlortetracycline, doxycycline, meclocycline, minocycline, demeclocycline, methacycline, tigecycline, and oxytetracycline (paragraphs 0024-0025).
Bonner does not exemplify a compound comprising both zidovudine and a tetracycline.
It would have been prima facie obvious before the effective filing date of the claimed invention to combine both zidovudine and a tetracycline in a composition to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select both zidovudine and a tetracycline in a composition for treatment of arthritis because Bonner teaches a composition that comprises an antiviral that is preferably a nucleoside analog such as zidovudine and a broad-spectrum antibiotic that is preferably a tetracycline such as tetracycline or doxycycline. One of ordinary skill in the art would have a reasonable expectation of success because Bonner teaches that the preferred antiviral is a nucleoside analog such as zidovudine and the preferred broad-spectrum antibiotic is a tetracycline.
Claims 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Bonner et al. (US 2006/0172956 A1, published 08/03/2006, see PTO-892) and Hopkins (WO 2015/153864 A2, published 10/08/2015, see PTO-892).
The teachings of Bonner are discussed above.
Bonner does not specifically teach that the tetracycline may be omadacycline.
Hopkins is drawn to methods of treating subjects for inflammatory conditions such as osteoarthritis by administering an effective amount of a tetracycline compound (claims 1 and 7). The tetracycline compound may be selected from doxycycline, minocycline, sarecycline, omadacycline, PTK-RA01 , PTK-MS01 , PTK-SMA2, tetracycline, chlortetracycline, oxytetracycline, demeclocycline, lymecycline, meclocycline, methacycline, rolitetracycline, clomocycline, metacycline, pipacycline, incyclinide, and derivatives thereof (claims 41 and 45).
It would have been prima facie obvious to combine Bonner and Hopkins before the effective filing date of the claimed invention by selecting omadacycline as taught by Hopkins as the tetracycline in the composition comprising a tetracycline and zidovudine as taught by Bonner to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select omadacycline because Hopkins teaches that omadacycline may be used to treat inflammatory disorders such as osteoarthritis. One of ordinary skill in the art would have a reasonable expectation of success because Bonner teachings a composition for treatment of osteoarthritis comprising zidovudine and a tetracycline and Hopkins teaches that omadacycline may be used to treat osteoarthritis.
Regarding instant claim 30, it is noted that the prior art does not teach that the composition can be used in the manner instantly claimed, wherein a combination comprising zidovudine, or the pharmaceutically acceptable derivative thereof, and omadacycline, or the pharmaceutically acceptable derivative or prodrug thereof, is synergistic in treating bacterial infections. However, the cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since the composition would be capable of performing the intended use. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Allowable Subject Matter
Claim 29 is allowed.
Instant claim 29 is drawn to a method of treating a microbial infection comprising administering to a subject a combination comprising zidovudine and omadacycline. The applicant provided data from Tian et al. (Antimicrobial Agents and Chemotherapy, published 08/28/2024, see PTO-892) that supported that the combination of zidovudine and omadacycline demonstrated unexpected synergy, rendering the claim nonobvious (Table 2, page 7).
The closest prior art, Bolen et al. (WO2018102397, published 06/07/2018, see PTO-892), teachings are discussed above. While Bolen does teach a composition that may comprise both zidovudine and omadacycline, Bolen does not exemplify the combination nor teach that the combination may exhibit a synergistic effect towards treating a microbial infection.
Consequently, the method of administering to a subject a combination of zidovudine and omadacycline demonstrated unexpected results rendering the claims non-obvious over the closest applicable prior art of Bolen et al.
Response to Arguments
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive.
Applicant argues that the provided data showing synergy in the combinations of zidovudine with doxycycline and zidovudine with omadacycline is commensurate in scope with the demonstrate unexpected results and that one of ordinary skill in the art could reasonably extend the behavior to the other tetracyclines. The argument is unpersuasive. As evidenced by Brochado, synergy is a species-specific activity. Brochado shows that two tetracyclines, doxycycline and minocycline, combined with the same second drug show different synergy behavior to bacterial strains. Further, Brochado even shows that the same tetracycline and drug combination, doxycycline and loperamide, shows different synergy behavior across two different strains of E. coli. This supports that synergy of antibiotics such as tetracyclines is unpredictable and one of ordinary skill in the art cannot extrapolate synergy data from one tetracycline combination on one bacteria species to additional tetracyclines and bacteria.
Regarding the rejection of instant claim 18 over Coates, applicant argues that the claim is limited to those that act synergistically in treating a bacterial infection and Coates does not teach that the combination of a tetracycline and zidovudine are synergistic. The argument is unpersuasive. Claim 18 is a product claim and therefore the intended use of treating a bacterial infection with a combination of tetracycline and zidovudine that is synergistic is not limiting. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Regarding the rejection of instant claim 18 over Bonner, applicant argues that Bonner teaches the treatment of arthritis, osteoarthritis, and bursitis by the antibiotic combinations and does not teach the use of the composition for treatment of a bacterial infection and does not teach that the combination of the zidovudine and tetracycline are synergistic. Further, Bonner does not specifically teach the combination of zidovudine and a tetracycline, nor is zidovudine a preferred antiviral. Applicant argues that there is no teaching, motivation, or suggestion in Bonner that would have led the skilled person to specifically select zidovudine. The argument is unpersuasive. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Bonner teaches the combination of an antiviral compound and a broad-spectrum antibiotic and teaches zidovudine and doxycycline in non-exhaustive examples of antiviral compounds and antibiotics. Bonner teaches that the preferred antiviral compound is a nucleoside analog and Bonner teaches zidovudine as one possible nucleoside analog and therefore, one of ordinary skill in the art would be motivated to choose zidovudine as one possible nucleoside analog as taught by Bonner. Further, claim 18 is a product claim and therefore the intended use of treating a bacterial infection with a combination of tetracycline and zidovudine that is synergistic is not limiting. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Regarding the rejection of instant claim 30 over Bonner and Hopkins, applicant argues that that Bolen omadacycline was only mentioned once as possible compositions for "the additional therapeutic agent" from among more than 300 disparate compositions and there is no teaching, motivation or suggestion in Hopkins that would have led a skilled person to specifically select omadacycline from the list of tetracyclines and to use in in the zidovudine-tetracycline combination of Bonner with any expectation that such a combination would display synergistic antibacterial activity. The argument is unpersuasive. 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, both Hopkins and Bonner are drawn to compositions for treating inflammatory conditions such as osteoarthritis with compositions that can comprise a tetracycline. Bonner teaches that the composition may comprise a nucleoside analog such as zidovudine and a tetracycline and Hopkins teaches that the tetracycline can be omadacycline.
Applicant argues that the Office Action dated 10/21/2025 acknowledges that the method of administering a combination of zidovudine and omadacycline (i.e. claim 29) demonstrates unexpected results, rendering that claim non-obvious over Bolen et al (WO2018102397Al) and suggested that the same reasoning should be applied to claim 30. The argument is unpersuasive. Instant claim 29 is a method claim while instant claim 30 is a product claim. The unexpected results are regarding the intended use of the product of instant claim 30 and as the intended use of the product is not structurally limiting the unexpected results do not overcome the prior art rejection.
Conclusion
Claim 29 is allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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