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 .
Applicant’s reply dated 12/19/2025 has been received.
Election/Restrictions
Applicant's election with traverse of Group III, claims 52,53,56-58,62,63,66-68,71,72,75,76 and 78 in the reply filed on 01/16/2024 was previously acknowledged and the restriction was made FINAL. Applicant continues to argue against the restriction in the reply dated 10/02/2024. Applicant referred to 37 CFR 1.144.
The traversal is on the ground(s) that the art does not teach fertile, homozygous double that produces sterile progeny mutant fish. This is not found persuasive because the groups lack unity of invention because there is no technical feature common to the groups. Group I is a method of generating a sterile, sex-determined fish that comprises use of fish comprising a mutation in a gene that specifies sexual differentiation in addition to mutation in a gene that specifies gamete function. This mutation is not part of the method of Group II and thus, a common technical feature is lacking. Group III is a fertile, not sterile fish. Group IV, as well, is a fertile fish, that does not comprise a mutation in a gene that specified sexual differentiation.
Group V, however, was rejoined with the elected Group III.
The remainder of the requirement is still deemed proper and is therefore made FINAL.
Claims 2,3,6-13,16-18,21-22,25-26,28,34-36,38,41-43,46-47,50,84-88,91-93,96-97,100, 119-120,123 and 126 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/28/2024.
Claim Rejections - 35 USC § 112
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.
The rejection of claims 52,53,56-58,62,63,66,68,72,75,76,78, 102-118 and 121-125 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of the amendments to the claims.
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.
The rejection of claims 52,53,56-58,62,63,66,68,72,75,76,78, and 122 ,125under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn in light of the Buchanan declaration dated 12/19/2025. However, the following scope of enablement rejection is necessary on the same grounds as the previous rejection and made in view of the data provided in the Buchanan declaration
Claims 52,53,56-58,68,72,76,78,122 and 125,127-130 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a fertile homozygous Elavl2 or Dnd1 mutant fish lacking endogenous germ cells for producing sterile, sex-determined fish, the fertile homozygous elavl2 or Dnd1 mutant fish having one or more transplanted germline stem cells as claimed, wherein the fertility of the fertile, homozygous Elavl2 or Dnd1 mutant fish is rescued by the one or more transplanted germline stem cells does not reasonably provide enablement for a homozygous mutated fish comprising a mutation in any gene other than Elavl2 or Dnd1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, make and/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The nature of the invention relates to generating sterile, monosex populations of fish. Claim 52 has been amended to clarify that it is the transplanted germline stem cells that comprise two mutations, m1 and m2. m1 is a mutation in a gene that leads to monosex culture. m2 is a mutation in a gene that leads to sterility. Double homozygous germ cells can rescue the germline of a fish lacking a germline because m1 and m2are not expressed in the germline but are necessary for somatic cells to generate fertile fish. Once this rescue occurs, the resulting fish would be fertile with oocytes and sperm that are double mutant.
Claim 52 is drawn to a fertile homozygous mutated fish comprising an exogenous germline comprising homozygous mutations in m1 and m2. m1 is a genus of genes that specify sexual differentiation (male vs female). m2 is a genus of genes that affects function of gametes (fertility).
As set forth in the previous office action (pages 8-10, 06/18/2025), the Specification falls short of supporting enablement of the claims. However, the Buchanan declaration dated 12/19/2025 supports the outcome of the methods taught in the Specification when Elavl2 or Dnd1 mutant fish are used. These homozygous mutants lack a germline but when germline stem cells are transplanted into larva, those cells can direct formation of and become part of the germline of the Elavl2 or Dnd1 mutant fish. When giving weight to the recited “for producing a sterile, sex-determined fish” given that the claim ends with rescue of fertility (see also claims 56-57), the only means of generating a sterile population from the claimed fish, would be for the claimed fish to not produce any germ cells that are wildtype for m1 or m2. This can only occur if the claimed fish entirely lacks its own m1+/m2+ germ cells. The Specification and Buchanan Declaration only supports such for Elavl2 and Dnd1 mutants. Yazawa (Marine Biotechnology (2024) 26:891–901) supports that Dnd1 mutants are completely sterile which renders it useful in the claimed invention. However, other mutations, such as vasa, result variable penetrance and incomplete sterility (Hartung, Mol Reprod Dev. 2014 October ; 81(10): 946–961. doi:10.1002/mrd.22414). It is also noted that the claims are not limited to mutation of a gene that leads to any effect on fertility. Thus, the only mutation in the host fish that is supported to lead to population of the germline by only transplanted germ cells are those supported by the Buchanan declaration.
Claims 102-106,109-118,121,124 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
These claims remain rejected for reasons of record. The Buchanan Declaration does not appear to apply to these claims. The m1m2 transplanted cells can rescue infertility in a fish lacking a germline because m1 and m2 are not expressed in germ cells. However, they are needed in the somatic cells for fertility. Thus, when m1m2 germline stem cells are transplanted into an m1m2 fish, the necessary signals will not be present. Claim 117-118 which use morpholino knockdown will lead to incomplete penetrance regardless of the gene and thus these claims remain rejected for reasons set forth above for mutations with incomplete penetrance.
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 VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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/VALARIE E BERTOGLIO/ Primary Examiner, Art Unit 1632
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