DETAILED ACTION
This action is in reply to papers filed 07/02/2026.
This is a second non-final action. The previous Office Action has been vacated.
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 .
Status of Claims
Claims 33-34, 36, 38-39, 41, 43, 45, 47-52, and 54-58 are pending.
Claims 53 is presently cancelled.
Claims 33-34, 36, and 47-52 are withdrawn from further consideration as being drawn to an invention non-elected without traverse in the reply filed on 12/22/2025.
Claims 38-39, 41, 43, 45, and 54-58 are examined on the merits herein.
Withdrawn Objections and Rejections
The objection to the Drawings on the ground of containing color drawing(s) without an accompanying Petition is withdrawn in light of the replacement drawings filed 07/02/2026, which are rendered in black and white.
The objection to the Drawings and Disclosure on the ground of nucleotide and/or amino acid sequences appearing in FIG. 2C and FIG. 2D is withdrawn in light of the replacement sheets for FIG. 2C and FIG. 2D filed 07/02/2026, which contain sequence identifiers.
The objection to the disclosure for containing an embedded hyperlink and/or other form of browser-executable code is withdrawn in light of the substitute specification filed 07/02/2026.
The objections to claims 39, 55, and 58 because of informalities are withdrawn in light of the amendment to said claims.
The rejection of claims 38-39, 41, 43, 45, and 54-58 under 35 U.S.C. 112(b) is withdrawn in light of the amendment to the claims.
The rejection of claim 39 under 35 U.S.C. 112(d) is withdrawn upon reconsideration.
The rejection of claims 38-39, 41, and 54-58 under 35 U.S.C. 112(a) is withdrawn in light of the amendment to claim 38 to incorporate limitations from cancelled claim 53 regarding reprogramming factors.
The cancellation of claim 53 renders any rejections thereof moot.
Claim Objections
Claims 38, 43, and 56 are objected to because of the following informalities:
Claim 38 recites the phrase “introducing a functional ASPA gene having a R132G mutation in the neural precursor cells” (lines 8-9). This phrase should be corrected to “introducing a functional ASPA gene having a R132G mutation into the neural precursor cells”.
Claim 43 is objected to for the same reason as set forth above for claim 38. Furthermore, the phrase “an R132G mutation” in claim 43 (line 2) should be corrected to “a R132G mutation” for sake of consistency with language in the other claims.
Claim 56 recites the phrase “wherein the functional ASPA gene is introduced by transducing the neural precursor cells with a vector comprising the functional ASPA gene” (lines 1-3). For the sake of clarity, this phrase should be corrected to “wherein the functional ASPA gene having the R132G mutation is introduced by transducing the neural precursor cells with a vector comprising the functional ASPA gene having the R132G mutation”.
Appropriate correction is required.
Claim Interpretation
Claims 43 and 45 are product-by-process claims. Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113. In the instant case, the method steps of claim 43 do not clearly impart additional structural limitations to the product of claim 43. Therefore, claim 43 is interpreted as “Neural precursor cells which express an exogenous functional R132G ASPA.”
Claim Rejections - 35 USC § 112(b)
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.
Claim 57 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.
Claim 57 contains the trademark/trade name TALEN. 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 transcription activator-like effector nuclease and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 56-57 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 56 is, in the second alternative, drawn to “The method of claim 38, wherein the functional ASPA gene is introduced by correcting a disease-causing ASPA mutation using gene editing technology.” This second alternative limitation improperly broadens the scope of claim 38, which recites “introducing a functional ASPA gene having a R132G mutation” (line 8; emphasis added), not correcting a disease-causing ASPA mutation, as recited by claim 56.
Claim 57 depends from said second alternative limitation in claim 56, and is therefore included in the rejection.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
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 38-39, 41, 43, 45, and 54-58 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.
This written description rejection is on the grounds of a functional ASPA gene having a R132G mutation as recited in claims 38 and 43, and wherein the functional ASPA gene having the R132G mutation comprises one or more additional mutations outside of the catalytic center as recited in claim 41. Each of these are addressed separately below.
From M.P.E.P. § 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
The skilled artisan cannot envision the detailed structure of all the fragments, derivatives or variants, that are encompassed by the claims, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method. Adequate written description requires more than a mere statement that it is part of the invention, and a reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification only provided the bovine sequence.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Applicant is reminded that Vas-Cath makes clear that the written description of 35 U.S.C. 112 is severable from its enablement provision [see p. 1115].
Regarding claims 38 and 43: Claim 38 is drawn to a method of producing ASPA neural precursor cells, wherein the method comprises introducing a functional ASPA gene having a R132G mutation in neural precursor cells to obtain genetically corrected neural precursor cells which express the functional ASPA gene having the R132G mutation. Claim 43 is drawn to neural precursor cells which express an exogenous functional ASPA gene having a R132G mutation.
Claims 38 and 43 recite a structure: an ASPA gene having a R132G mutation. Claims 38 and 43 also recite a function: a functional ASPA gene having a R132G mutation. Thus, the claims are drawn to a method (claim 38) or product (claim 43) comprising a very large genus of an ASPA gene having the claimed function.
The instant specification discloses that “a "functional" ASPA or ASPA gene means that the amino acid sequence or the nucleotide sequence of ASPA may contain one or more mutations; however, the activities of the mutated ASPA are not substantially reduced compared to the wild type ASPA. In some embodiments, a functional ASPA retains at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 100%, at least 105%, at least 110%, at least 115%, at least 120%, or at least 125% activities of the wild type ASPA” (p 20, para 48).
Beyond an ASPA amino acid sequence comprising a R132G mutation as set forth in SEQ ID NO: 3 (p 22, para 53), the specification discloses a nucleotide sequence termed hASPA-R132G (set forth in SEQ ID NO: 2), which comprises a R132G mutation (A to G point mutation at nucleotide 394) and a synonymous T to C mutation at nucleotide 735 (p 21, para 52). However, aside from the T735C mutation in the hASPA-R132G nucleotide sequence (set forth in SEQ ID NO: 2), the specification does not disclose or suggest what the “one or more mutations” made to the amino acid or nucleotide sequence of ASPA are, such that the mutated ASPA exhibits activities that are not substantially reduced compared to wild type ASPA.
The prior art is unpredictable. WO 2017/223373 A1 (Shi) teaches a method of producing ASPA neural precursor cells, comprising reprogramming or converting somatic cells isolated from a subject suffering from Canavan disease into induced pluripotent stem cells (iPSCs); differentiating the iPSCs into neural precursor cells; and introducing wild type ASPA gene in the neural precursor cells to obtain genetically corrected neural precursor cells which express wild type ASPA (para 10, 49; claim 25). Shi teaches that iPSCs converted from patient somatic cells contain one or more mutations in the ASPA protein, such as A305E, E285A, or G176E, and that these mutation-carrying iPSCs are genetically corrected to express exogenous wild type ASPA protein and exhibit ASPA enzymatic activities (para 47, 75). The functional ASPA gene taught in Shi is one that encodes a wild type ASPA protein. Shi does not teach what mutations may be made to an ASPA gene, such that the ASPA gene retains its function as a functional ASPA gene, as required by the instant claims.
Thus, neither the specification nor the prior art establishes a structure-function relationship wherein an ASPA gene having a R132G mutation would be capable of functioning as a functional ASPA gene having a R132G mutation, as claimed, with any degree of predictability.
Regarding claim 41: Claim 41 is drawn to the method of claim 38, wherein the functional ASPA gene having the R132G mutation comprises one or more mutations outside of the catalytic center.
Claim 41 recites a structure: an ASPA gene comprising one or more mutations outside of the catalytic center, wherein the catalytic center comprises residues Arg63, Asn70, Arg71, Tyr164, Arg168, Glu178, and Tyr288. Claim 41 also recites a function: a functional ASPA gene comprising one or more mutations outside of the catalytic center. Thus, the claim is drawn to a method comprising a very large genus of an ASPA gene having the claimed function.
The instant specification discloses the R132G mutation as an example of a mutation outside of the catalytic center of ASPA, wherein the mutation does not substantially decrease the ASPA activity (p 20, para 49; p 28, para 69; p 52, para 99). The specification discloses that ASPA binds one atom of Zn per monomer, and that the amino acid residues involved in Zn binding include His21, Glu24, and His116 (p 21, para 51). The specification does not disclose or suggest what other mutations may be made outside of the catalytic center aside from R132G, or what other amino acid residues must remain unchanged aside from His21, Glu24, and His116, such that the ASPA gene retains the function of being a functional ASPA gene.
The prior art is unpredictable. As set forth above, WO 2017/223373 A1 (Shi) teaches that iPSCs converted from patient somatic cells contain one or more mutations in the ASPA protein, such as A305E, E285A, or G176E, and that these mutation-carrying iPSCs are genetically corrected to express exogenous wild type ASPA protein and exhibit ASPA enzymatic activities (para 47, 75). These three mutations, which fall outside of the catalytic center and result in a non-functional ASPA gene, represent mutations at merely three residues of the ASPA polypeptide, which comprises 313 residues. Shi does not provide a sufficient representative number of species of mutations made to an ASPA gene outside of the catalytic center, such that the ASPA gene retains its function as a functional ASPA gene, as required by the instant claim.
Thus, neither the specification nor the prior art establishes a structure-function relationship wherein an ASPA gene comprising one or more mutations outside of the catalytic center, wherein the catalytic center comprises residues Arg63, Asn70, Arg71, Tyr164, Arg168, Glu178, and Tyr288, would be capable of functioning as a functional ASPA gene, as claimed, with any degree of predictability.
Claims 39, 41, 45, and 54-58 are included in the rejection because they depend from claim 38 or 43.
Relevant Prior Art
The following prior art, which is not relied upon for claim rejections, is made of record:
WO 2017/223373 A1 (hereinafter Shi) is the closest prior art to claim 38. Shi teaches a method of producing ASPA neural precursor cells, comprising reprogramming or converting somatic cells isolated from a subject suffering from Canavan disease into induced pluripotent stem cells (iPSCs); differentiating the iPSCs into neural precursor cells; and introducing wild type ASPA gene in the neural precursor cells to obtain genetically corrected neural precursor cells which express wild type ASPA (para 10, 49; claim 25). However, Shi does not teach introducing a functional ASPA gene having a R132G mutation (R132G ASPA) in the neural precursor cells to obtain genetically corrected neural precursor cells which express R132G ASPA, as required by instant claim 38.
Conclusion
No claim is allowed.
Claims 38-39, 41, 43, 45, and 54-58 appear to be free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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