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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09 June 2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-11, 16, and 21, and species election 1. iPS cells and 2. an insertion site on chromosome 13q12.12 between nucleotides -24,083,331 - 24,083,332 bp from the P-terminus in the reply filed on 05/13/2025 is acknowledged.
Claims 7 and 8 require cells other than the elected iPS cells, therefore, were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, claims 12-15 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/13/2025.
The Official Action mailed 13 June 2025 partially withdrew the species election, only as it pertains to the insertion site.
In the Official action mailed on 23 January 2026, claims 9 and 10 were withdrawn by original presentation.
Therefore, claims 9-10, 12-15, and 17-20 are withdrawn from consideration as being directed to a nonelected invention and claims 7-8 are withdrawn from consideration as being directed to a nonelected species.
Claim Status
Claim 1 has been amended, claims 7-10, 12-15, and 17-20 have been withdrawn, claims 2-4 and 16 were previously canceled, and claims 1, 5-6, 11, and 21 have been examined on their merits.
Withdrawn Rejections
Applicant’s arguments, see remarks, filed 09 June 2026, with respect to claims 1, 5, 6, 11, and 21 have been fully considered and are persuasive. Specifically, the amendments to claim 1. The rejection under 35 U.S.C. § 103 of claims 1, 5, 6, 11, and 21 has been withdrawn.
Claim Objections
This is a new objection.
Claim 21 is objected to for an improper incorporation by reference. The attempt to incorporate subject matter into this application by reference to “Genbank accession number BX648244” is ineffective because there is no canonical sequence for this accession number because the sequence can be modified at any time with a different version. Therefore, this reference point represents a specific reference to a vague entity that is a moving object depending on the genome build number and/or version number and does not represent a specific sequence.
The incorporation by reference will not be effective until correction is made to comply with 37 CFR 1.57(c), (d), or (e). If the incorporated material is relied upon to meet any outstanding objection, rejection, or other requirement imposed by the Office, the correction must be made within any time period set by the Office for responding to the objection, rejection, or other requirement for the incorporation to be effective. Compliance will not be held in abeyance with respect to responding to the objection, rejection, or other requirement for the incorporation to be effective. In no case may the correction be made later than the close of prosecution as defined in 37 CFR 1.114(b), or abandonment of the application, whichever occurs earlier.
Any correction inserting material by amendment that was previously incorporated by reference must be accompanied by a statement that the material being inserted is the material incorporated by reference and the amendment contains no new matter. 37 CFR 1.57(g).
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.
Claims 1, 5-6, 11, and 21 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 is a lack of written description rejection.
This is a new rejection necessitated by Applicant’s amendments to the claims.
Claim 1 recites a cell comprising a genetic modification within the SPATA13 gene on chromosome 13q12.12, wherein the cell is a human cell, wherein the genetic modification is an inserted, stably integrated transgene encoding a protein of interest, wherein the transgene is stably expressed without causing significant alterations in the expression of endogenous genes in a cell relative to a corresponding human cell of the same type lacking the integrated transgene.
Accordingly, the claims are directed to a structurally-undisclosed genus of protein expression functionally-defined as not causing alterations in the expression of endogenous genes. The cell of claim 1 may broadly comprise any type of human cell and any stably integrated transgene at any location on the SPATA13 gene, which encodes a protein.
An adequate written description of a genetically modified cell that lacks an undefined alteration in endogenous gene expression requires more than a mere statement that it is part of the invention. What is required is either (1) a description of a common core structure shared among the members (species) of the functionally described genus or (2) a disclosure of a representative number of species of the functionally described genus. It is not sufficient to define a genus of stably integrated transgenes encoding a protein of interest solely by its desired biological property, i.e., the lack of alterations in the expression of any endogenous genes, to include the gene wherein the transgene is to be inserted. Thus, claiming all human cells genetically modified within the SPATA13 that do not alter expression of endogenous gene expression, without defining what means will do, or without disclosing a representative number of species, is not in compliance with the written description requirement.
Although the specification contemplates the likelihood of any gene being inserted into the SPATA13 gene at a specific range of 13q12.12 not creating alterations in endogenous gene expression, the only example of this process exhibiting an apparent lack of alteration in endogenous gene expression is the cmycERtam gene in the creation of the CTX0E03 neural stem cell line (instant specification at p. 16). Also disclosed in the instant specification at p. 18, since the CTX0E03 cell line was generated using a retroviral vector, it is important to consider the possibility that insertional mutagenesis and oncogenic activation might occur. Therefore, the stable integration of a transgene could alter the expression of oncogenic genes to include SPATA13. The assumption that the SPATA13 gene has no known function (instant specification, p. 21) does not provide sufficient description for one of ordinary skill to stably insert any transgene in any human cell at any location on the SPATA13 gene and expect the result of no alteration in expression of any endogenous gene when considering the complex molecular pathways in cells. Additionally, the instant disclosure does not provide the requisite metric to determine how this lack of alteration in other endogenous genes would be determined, as discussed in the 112(b) rejection below.
Accordingly, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of stably inserting any transgene in any human cell at any location on the SPATA13 gene and expect the result of no alteration in expression of any endogenous gene at the time the application was filed.
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 1, 5-6, 11, and 21 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.
This is a new rejection necessitated by Applicant’s amendments to the claims.
The term “significant” in claim 1 is a relative term which renders the claim indefinite. The term “significant” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Without any standard, measurement, or functional definition, and no recognized art standard it is not clear what the scope of “significant” would include or exclude for the claimed method. The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973).
Additionally, claim 1 appears to contradict itself as inserting any transgene within SPATA13, which is an endogenous gene, could cause significant alterations in the expression of SPATA13. This contradiction also renders the scope of the claim indefinite.
Claim 21, option c states within the third intron of a cDNA, however, cDNA does not comprise introns. Thus, renders the scope of the claim indefinite.
Additionally, claim 21 (c) references a Genbank accession number and nucleotide coordinates are considered reference points representing a specific reference to a vague entity that is a moving object depending on the specific genome build number. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)). Claim 21 recites “Genbank accession number BX648244”. There is no canonical sequence for this accession number because the sequence can be modified at any time with a different version. Therefore, this reference point represents a specific reference to a vague entity that is a moving object depending on the genome build number and/or version number and does not represent a specific sequence.
The accession number should either be removed or replaced by a SEQ ID NO.
Furthermore, claim 21 (d-g) reference nucleotide locations relative to the P-terminus and nucleotide coordinates are considered reference points representing a specific reference to a vague entity that is a moving object depending on the specific genome build number. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)). These locations would vary depending on the genome build number and could also vary depending on the type of cell. Therefore, this reference point represents a specific reference to a vague entity that is a moving object depending on the genome build number and/or type of cell and does not represent a specific sequence.
The dependent claims are included in the rejection because they do not remedy the issues.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICHOLAS A. HUMPHRIES whose telephone number is (703)756-5556. The examiner can normally be reached Monday - Friday, 7:30am - 4:30 pm.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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