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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 07/14/2026 has been entered.
Claims 136-141 are added and claims 140-141 are withdrawn.
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Claims 2,3,6-13,16-18,21-22,25-26,28,34-36,38,41-43,46-47,50,84-88,91-93,96-97,100, 119-120,123 and 126,140-141 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 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 previous scope of enablement rejection is withdrawn in favor of the following new rejection that is based on the same grounds that the claimed fish, which is essentially a ‘host’ fish hosting mutant germ cells and is essentially a producer of sterile, monosex populations cannot be any “fertile homozygous mutated fish”.
Claims 52,53,56-58,68,72,76,78,122 and 125,127-130 and 138-139 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 mutant fish lacking endogenous germ cells as a result of the mutation for producing sterile, sex-determined fish, the fertile homozygous mutant fish having one or more transplanted germline stem cells as claimed, wherein the fertility of the fertile, homozygous 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 its own germ cells. 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. The Buchanan declaration dated 7/14/26 supports the outcome of the methods taught in the Specification when nanos3 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 mutant fish. Claim 52 is drawn to a “fertile homozygous mutant fish” and recites that the fertility of the fish has been rescued. However, the mutation is not limited to one that leads to a lack of endogenous germ cells. In light of the Buchanan declarations and the teachings of Yazawa (2024, of record), the enabled breadth is no longer limited to specific mutations. However, the mutations should be required to lead not a lack of endogenous germ cells in the gonads of the claimed 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 and should be explicitly recited such that the “mutated fish” does not read on mutation of any gene, but a gene that leads to a lack of germ cells in the gonad.
The rejection of claims 102-106,109-118,121,124 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 is withdrawn in light of the amendments to claim 102.
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.
Claims 52,53,56-58,68,72,76,78,102-106,109-118,122,124,125 and 127-137 are 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.
Claim 52 is unclear at (i). It is not clear if the mutation disrupts synthesis of estrogen or if the mutation is in a gene that normally disrupts synthesis of androgen. For the same reason, step (iii) is also unclear. See also the rejection of claim 102, below.
Claim 56 is unclear because it recites method steps while depending from a product claim. It is not clear if this is meant to be a product-by-process type limitation. Similarly, claims 117 and 118 are unclear. It is presumed that the “germ cell-less” fish in claims 56,117 and 118 are the claimed “A fertile homozygous mutated fish” of claim 52. However, this needs to be made clear. As it is now, there is no correlation between the germ cell-less fish of the dependent claims and the product of claim 52.
Claim 58 is unclear as independent claim 52 is interpreted that there is a lack of endogenous germ cells in the claimed fish and this characteristic is the result of a genetic mutation. Thus, it is not clear if claim 58 is inferring the mutation is not the clause of germ cell loss in claim 52 or if this additional method step did or did not occur. As well, claim 58 recites a product by process type limitation and it is only the effect of the process that is taken into consideration.
Claims 117 and 118 are also unclear because the fish are made germ cell-less using morpholinos. However, claim 52 indicates that the germline of the claimed fish is rescued and the fish is “fertile homozygous mutated fish”. This implies that the fish lacks its own germline as an effect of mutation. Morpholino knockdown is not a mutation.
Claim 68 and 127 are unclear because claim 68 recites “…genes that disrupt the synthesis of androgen…is one or more genes that disrupt expression of (a) aromatase Cyp19a1a…”. Claim 127 recites “gene that disrupts expression of aromatase is…cyp19a1a.” If the mutation of claim 68 is in a gene that disrupts the expression of aromatase Cyp19a1a then the mutation cannot be in cyp19a1a because cyp19a1a is aromatase, not an aromatase disruptor. This lack of clarity may be related to the lack of clarity in claim 52.
Claim 102 is unclear in the phrases that use the term “disrupts” For example, “a mutation in a gene that disrupts oogenesis” is an unclear phrase with regard to whether the mutation disrupts oogenesis or the mutation is in a gene that disrupts oogenesis.
Claim 131 is unclear because claim 110 recites that the gene can be on that disrupts expression of Cyp19a1a the claim 131, depending from 110, recites that the gene that disrupts expression of Cypa1a can be cyp19a1a. Cyp19a1a does not disrupt the expression of itself. The same is the case for claim 132.
Claim 135 is unclear because FSHR does not disrupt synthesis of estrogen.
Claim 138 is unclear because if the germ cell-less phenotype is caused by morpholino, it becomes unclear what the mutation is and if that mutation also causes germ cell absence.
Claims 53,56-58,68,72,76,78,117,118,122,125 and 127-130,138-139 are unclear given their dependency from claim 52.
Claims 103-106,109-116,121-122,124-125,131-137 are unclear given their dependency from claim 102.
Conclusion
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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