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 .
Response to Amendment
This action is written in response to applicant’s amendments received on 2/2/26
Any objection or rejection not reiterated herein has been overcome by amendment.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-10 the reply filed on 8/7/24 is acknowledged.
Claim 10 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 7/1/25.
Priority
Application claims priority to 63/191,046 provisional application with an effective filing date of 5/20/21. Claims of the instant application are supported by the provisional application and thus have a priority date of 5/20/21.
Claim Rejections - 35 USC § 112(a) (new matter)
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.
New rejection necessitated by amendment. Claims 1-4, 7-9, and 13-17 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.
Regarding claim 1, the claim is amended to add “transporting molecular information from the ingested bacteria across an intestinal membrane of the nematode, the nematode selected based on a responsiveness to the molecular information for functional rescue”. There is no support in the specification for “molecular information” or selecting the nematode based on a responsiveness to the molecular information for functional rescue. The claims thus comprise new matter.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
New rejection necessitated by amendment. Claims 1-4, 7-9, and 13-17 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the claim requires “generating an expression vector” and a “recombinant neuropeptide plasmid” which is then inserted into bacteria and fed to nematodes where the mRNA is delivered to the subject and translated into the neuropeptide indicated in the last line of claim 1. As the delivery of the mRNA is via the “recombinant neuropeptide plasmid“, this could be considered an expression vector as well. It is therefore unclear if the “expression vector” and the “recombinant neuropeptide plasmid” are supposed to be the same plasmid or if the invention requires two expression vectors. For examination purposes, any vector which is capable of producing a peptide will be considered to meet instant claim limitations.
Claims 2-4, 7-9 and 13-14 fail to remedy this deficiency.
Further regarding claim 1, the claim requires “transporting molecular information” There are no details in the specification as to what the “molecular information” is and the term is not defined by the claim. The molecular information could be protein, RNA, DNA, lipids, or chemical compounds among others. Therefore, one of ordinary skill in the arts is unable to determine the metes and bounds of the claims.
Further regarding claim 1, the claim requires “transporting molecular information from the ingested bacteria across an intestinal membrane”. How this is accomplished is not disclosed by either the specification or the claims. This step could be inherent as a result of the nematode eating the bacteria or could be accomplished by the incorporation of some sort of transport signal. The claims and specification do not describe how this is accomplished and the claim is unclear (e.g., the transporting of molecular information could include any of myriad indirect cell signaling processes, and it is unclear what steps are required by the claims).
Claim 15 contains the trademark/trade name DH5α. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe E. coli and, accordingly, the identification/description is indefinite.
Further regarding claim 15, it is unclear if the claimed altered phenotypes is in reference to the peptide, the e. coli, or the nematode.
Regarding claim 16, the claim requires “selecting the mRNA based on uptake of INS-6 mRNA directly”. It is unclear what the relationship is between mRNA and the INS-6 mRNA is. It is unclear if the mRNAs are the same, how the uptake of INS-6 mRNA is determined, how the rate of uptake is determined, and what “uptake of INS-6 mRNA directly” means. This claim is too unclear to be properly examined.
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.
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 1-4, 7-9, 13-14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Reilly (Neuromodulation of Sex-Specific Pheromone-Mediated Behaviors. : Worcester Polytechnic Institute) and Sinay (of record).
While Reilly shares an inventor with instant application, as evidenced by Reilly date, the dissertation was published on 5/10/2020 (appendix). This is more than one year before instant filing date and therefore Reilly is valid prior art under 35 U.S.C. 102(a)(1). Further, as evidenced by Embargo and No embargo pictures obtained from WPI’s dissertation database, Reilley was not under a publication embargo and was available to the public on 5/10/2020 (appendix). Claim 7 is further evidenced by Promoter (accessed from https://www.genome.gov/genetics-glossary/Promoter#:~:text=A%20promoter%2C%20as%20related%20to,initiate%20transcription%20of%20that%20gene on 2/13/25). Claim 13 is further evidenced by Reilly scramble (appendix).
Modified rejection necessitated by amendment. Regarding claims 1, 4, and 17, Reilly studies neuropeptides in C. elegans (abstract). Reilly studies the FLP-3 neuropeptides (abstract). Reilly studies the FLP-3 neuropeptide using Gateway cloning in expression vectors (p204 “Rescue of Individual FLP-3 Peptides by Feeding Reveals a Specific Subset of Peptides Required for Attractive Behavior”). As evidenced by instant specification [0008], Gateway cloning is a high throughput screening method. Reilley teaches the nucleic acid sequence is amplified using primers comprising restriction (cleavage) sites (recombining nucleic acid sequence by adding cleavage sites) (p211 “vector generation”). Reilly teaches that DNA sequences can be inserted into expression plasmids (recombinant/expression neuropeptide plasmids) (p211” vector generation”). Reilly teaches that the plasmids can be introduced into E. coli and fed to C. elegans (transformed neuropeptide bacterial feed) (p343 “A Novel Mode of Peptide Rescue: Feeding”). Reilly teaches the C. elegans fed E. coli expressing the peptide can be screened for behavior and that behavior can be restored to wildtype levels in null mutants (nematode selected based on a responsiveness to molecular information, identifying neuropeptide based on elucidated function, delivering the mRNA, translating the mRNA to neuropeptide in the subject) (fig 28). As this is a neuropeptide and the behavior can be restored to the wt levels via feeding the nematodes, one of ordinary skill in the arts understands that a molecular signal and/or a molecule (molecular information) is transported from the gut of the nematode to the neurological system (across an intestinal membrane). Reilly teaches that their feeding strategy is robust technology that allows for the rapid generation of rescue constructs (p343 “A Novel Mode of Peptide Rescue: Feeding” section).
Reilly does not explicitly teach the TRH-1A peptide.
Sinay studies TRH neuropeptides (abstract). Sinay teaches that TRH-1 is studied in C. elegans (“results” section). Sinay teaches that TRH-1 is processed into two peptides, one of which is GRELF-NH2 (fig 1). As evidenced by instant specification [0071], this peptide is TRH-1A. Sinay teaches that their study provides a basis for further studies on TRH (pE4073 left column 2nd full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to screen TRH-1A of Sinay in the screening method of Reilly. One of ordinary skill in the art would be motivated to do so because Reilly teaches their method is rapid and robust and Sinay teaches that TRH should be further studied. Further, one of ordinary skill in the art would be motivated to do so because these neuropeptides have been successfully studied in C. elegans, 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 Reilly and Sinay are in the same field of endeavor of C. elegans neuropeptides.
Regarding claim 2, Reilley teaches the cutsites are added upstream and downstream of the gene of the neuropeptide (5’ and 3’, peptide cleavage site) (p211 “vector generation”).
Regarding claim 3, Reilly teaches promoters can be used (p211-212 “vector generation”). As evidenced by Promoter, promoters are upstream of the gene (p2).
Regarding claim 7, Reilly teaches that the E. coli strain can be changed depending on feeding preferences (properties) (p370 2nd full paragraph).
Regarding claim 8, Reilly teaches that pDEST-527 can be used for the rescue vectors (p370 third full paragraph).
Regarding claim 9, Reilly teaches that SCRAMBLE (control) vectors can be used as well (fig 28).
Regarding claim 13, Reilly teaches that the SCRAMBLE control can be amplified using a primer (supplemental table 3). When this primer is translated it is a 100% match to the claimed amino acid sequence (appendix). Sinay teaches that scrambled peptides with a -NH2 terminus can be used (fig 2).
Regarding claim 14, Reilley teaches the cutsites are added upstream and downstream of the gene of the neuropeptide (TRH-1A, 5’ and 3’, peptide cleavage site) (p211 “vector generation”). Reilly teaches that pDEST-527 can be used for the rescue vectors (p370 third full paragraph). As evidenced by instant specification [0028], pDEST-527 comprises a T7-promoter sequence.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Reilly (Neuromodulation of Sex-Specific Pheromone-Mediated Behaviors. : Worcester Polytechnic Institute) and Sinay (of record), as applied to claims 1-4, 7-9, 13-14 and 17 above, and further in view of Zhou, Mengzhou, et al. "Lactobacillus zeae protects Caenorhabditis elegans from enterotoxigenic Escherichia coli-caused death by inhibiting enterotoxin gene expression of the pathogen." PLoS One 9.2 (2014): e89004.
Regarding claim 15, Reilly and Sinay do not explicitly teach feeding DH5a cells.
Zhou teaches DH5α cells comprising enterotoxin peptides can be fed to C. elegans and their death (phenotype) observed (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use DH5α cells as taught by Zhou in the feeding method of Reilly and Sinay above. One of ordinary skill in the art would be motivated to do so because DH5α E. coli have been successfully used to feed C. elegans, 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. Further, this is a simple of substitution of known strains of E. coli. There would be a reasonable expectation of success as both Reilly and Zhou are in the same field of endeavor of feeding E. coli to C. elegans.
Response to Arguments
Applicant's arguments filed 2/2/26 have been fully considered but they are not persuasive. Applicant argues that Reilly does not teach transforming a neuropeptide into a bacterial cell or identifying at least one neuropeptide and recombining a nucleic acid sequence of the neuropeptide to obtain a recombinant neuropeptide (p2 5th paragraph). Reilly teaches that DNA sequences can be inserted into expression plasmids (recombinant/expression neuropeptide plasmids) (p211” vector generation”). Reilly teaches that the plasmids can be introduced into E. coli and fed to C. elegans (transformed neuropeptide bacterial feed) (p343 “A Novel Mode of Peptide Rescue: Feeding”). Reilly teaches the C. elegans fed E. coli expressing the peptide can be screened for behavior and that behavior can be restored to wildtype levels in null mutants (nematode selected based on a responsiveness to molecular information, identifying neuropeptide based on elucidated function, delivering the mRNA, translating the mRNA to neuropeptide in the subject) (fig 28). See the rejection above for details.
Applicant argues that claim 1 requires additional limitations (p2 bridging paragraph and p3 first full paragraph). As discussed above these limitations are not supported by the specification and Reilly teaches the claimed limitations. See the rejection above for details.
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 on 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