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
Applicant’s election without traverse of Group 1, claims 1-2, 6, 9, 12-15, 18, 19, 22, 24, 26, and 56-61 the reply filed on 6/25/25 is acknowledged.. Election was made without traverse in the reply filed on 6/25/25.
Applicant’s election of species of a hydroxylase in protein synthesis, hydroxylase as the enzyme, OxyS protein comprising a mutation at L44, and K2 as the toxin in the reply filed on 6/25/25 is acknowledged.
The elected OxyS point mutation was not found so other positions were searched.
Priority
Application claims priority to 62/933,249 provisional application with an effective filing date of 11/8/19. Claims 1-2, 6, 9, 12-15, 19, 22, 24, 56-60 and 62 of the instant application are supported by the provisional application and thus have a priority date of 11/8/19.
Instant claims 18 and 26 have support in application PCT/US20/59747 with a priority date of 11/9/20.
Information Disclosure Statement
The IDS filed on 5/20/22 has been fully considered except where references have been lined through.
Response to Amendment
This action is written in response to applicant’s amendments received on 2/27/26.
The rejection of the claims under 35 USC 112(a) and (b) is overcome by amendment.
The rejection of the claims under 35 USC 102 is overcome by amendment.
Amended claims 1-2, 6, 9, 12-15, 18-19, 22, 24, 26, 56, 60-64 are under examination herein.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
New rejection necessitated by amendment Claims 1, 2, 22, 24, 26, 56, 60 and 62 are rejected under 35 U.S.C. 102(a)(2)as being anticipated by of Rowley (WO2020257625A1). While Rowley was published after the filing date of instant application, it claims priority to 6/21/19 and therefore is valid prior art under 35 U.S.C. 102(a)(2).
Regarding claims 1, 2, 22, 24, 26, and 62, Rowley teaches killer toxins with activity against organisms (abstract). Rowley teaches that the killer toxin can be expressed in a host cell (abstract). Rowley teaches the toxin can be a K2 toxin (abstract). Rowley teaches the K2 toxin is a peptide (p2 lines 18-27). Rowley teaches their invention has a high therapeutic index (p39 line 27-p40 line 2). Rowley teaches the host cell can be Saccharomyces cerevisiae (claim 8). Rowley teaches the composition can be administered with pharmaceutically acceptable carriers (pharmaceutical composition) (claim 17). Rowley teaches the therapeutic molecule is secreted (fig 3).
Regarding claims 56 and 60, Rowley teaches administration can be topical (not administered to digestive system) (abstract).
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 6, 9, 12, 13, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Rowley (WO2020257625A1), as applied to claims 1, 2, 22, 24, 26, 56,60 and 62 above, and further in view of Li (Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an α-hydroxylation-dependent Claisen-like cyclization catalyzed by a dimanganese thioesterase." Journal of the American Chemical Society 133.39 (2011): 15773-15785).
Regarding claim 6, and 9, Rowley does not explicitly teach that the therapeutic molecule is a small molecule. Rowley teaches that the pharmaceutical composition can include other therapeutic agents including antibiotics (p34 lines 3-15).
Li teaches a gene cluster responsible for the production of compound 1 (TAN-1612 from table 1) (abstract). Li teaches that TAN-1612 is a tetracycline (antibiotic) (abstract, introduction) Li teaches this gene cluster can be expressed in Saccharomyces cerevisiae (abstract). Li teaches that the media was analyzed for the production of the compounds (indicated compound secreted). (p15775-15776 “Reconstitution and Investigation of the Biosynthetic Pathway of 1 in S. cerevisiae” section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the antibiotic producing yeast of Li in the pharmaceutical composition of Rowley. One of ordinary skill in the art would be motivated to do so because Rowley teaches that other therapeutic agents can be included in the composition. There would be a reasonable expectation of success as both Rowley and Li are in the same field of endeavor of genetically engineered yeast.
Regarding claims 12 and 13, Li teaches that AdaA and AdaC can be used (p15776 “Construction of E. coli Expression Plasmids” section).
Regarding claim 64, Rowley teaches that that the effective amount depends on a wide variety of factors, but can easily determined by one skilled in the arts or via routine experimentation (p12-13 “effective amounts”). Rowley teaches the toxin (therapeutic molecule) can be at 10g/L (example 4). This overlaps the claimed amount and therefore the claimed amount if obvious. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
Claims 14, 15, 18, 19 and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Rowley (WO2020257625A1) and Li (Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an α-hydroxylation-dependent Claisen-like cyclization catalyzed by a dimanganese thioesterase." Journal of the American Chemical Society 133.39 (2011): 15773-15785), as applied to claims 6, 9, 12-13 above, in view of Petkovic (US20100035847A1).
Regarding claims 14, 15, and 19, Rowley and Li do not teach the use of an OxyS protein.
Petkovic teaches genes for biosynthesis of tetracycline (title). Petkovic teaches that modified tetracyclines have been found to have improved pharmacological properties ([0002]). Petkovic teaches that their invention is directed towards creating novel tetracyclines ([0007]). Petkovic teaches that the invention can comprise OxyS (SEQ ID 23, [0071]). Petkovic teaches that their invention can produce tetracyclines with a variety of useful functions including treatment of bacterial or fungal infections, treatment of malaria, a neurodegenerative disease, Parkinson's disease, Huntington's, disease, periodontitis, an autoimmune condition, multiple sclerosis, atherosclerosis, rheumatoid arthritis, osteoporosis, tumour invasion, cancer and inflammatory states. ([0063-00064]). Petkovic teaches the genes can be expressed in a host cell ([0014]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate an OxyS protein as taught by Petkovic in the bacterium of Li. One of ordinary skill in the art would be motivated to do so because Petkovic teaches that tetracyclines produced using that gene can have a wide variety of useful functions. There would be a reasonable expectation of success as both Li and Petkovic are in the same field of endeavor of biosynthesis of tetracyclines.
Regarding claims 18 and 61, Petkovic teaches the proteins used in the invention can be 80% similar to SEQ ID 23 (OxyS) ([0034]). While Petkovic does not teach the claimed positions, it would be a matter of routine experimentation to arrive at the claimed positions given the teachings of Petkovic.
Claim 63 is rejected under 35 U.S.C. 103 as being unpatentable over Rowley (WO2020257625A1), as applied to claims 1, 2, 22, 24, 26, 56,60 and 62 above, and further in view of Niimi, Masakazu, et al. "Functional analysis of fungal drug efflux transporters by heterologous expression in Saccharomyces cerevisiae." Japanese journal of infectious diseases 58.1 (2005): 1-7.
Regarding claim 63, Rowley does not explicitly teach a heterologous efflux pump.
Nimmi teaches efflux transporters (pumps) that are heterologously expressed in Saccharomyces cerevisiae (title, abstract). Niimi teaches that their system is versatile, stable, and a powerful tool for studies going forward (conclusion).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include an efflux pump in the composition of Rowley as taught by Niimi. One of ordinary skill in the art would be motivated to do so because Niimi teaches that their system is versatile, stable, and a powerful tool for studies going forward. Further, one of ordinary skill in the art would be motivated to do so because these efflux pumps have been successfully used in genetically engineered Saccharomyces cerevisiae 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 yielded nothing more than predictable results to one of ordinary skill in the art. There would be a reasonable expectation of success as both Rowley and Niimi are in the same field of endeavor of genetically engineered Saccharomyces cerevisiae.
Response to Arguments
Applicant’s arguments with respect to the claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant argues that Petkovic does not teach desired chemical modifications to the tetracycline (p11-23 bridging paragraph). MPEP 2145 teaches that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims.
Applicant argues that this is an unexpected result (p12 first full paragraph). This argument relies upon unclaimed features and could be more persuasive if the argued limitations were present in the claims.
Applicant agues that Li does not teach the secretion of the molecule (p14 first partial paragraph). Li teaches that the media was analyzed for the production of the compounds (indicated compound secreted). (p15775-15776 “Reconstitution and Investigation of the Biosynthetic Pathway of 1 in S. cerevisiae” section). Further, Rowley teaches the secretion of therapeutic compounds.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TREVOR L KANE whose telephone number is (571)272-0265. The examiner can normally be reached M-F 7:00 am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TREVOR KANE/ Examiner, Art Unit 1657
/ROBERT J YAMASAKI/ Primary Examiner, Art Unit 1657
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