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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-14 in the reply filed on 2/16/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 15-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 2/16/2026.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/926,348 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed method encompasses the same operable steps in claims 1 and 11 of ‘348. Specifically, the instant claims encompass the same sequences that impact cell therapy efficacy as claimed in ‘348. Further dependent claims 2-10 and 12-15 of ‘348 encompass the same limitations as set forth in instant claims 2-14.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 1-14 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.
When the claims are analyzed in light of the specification, the instant invention encompasses any RNA-encoding sequence that is beneficial to cell therapy efficacy and any RNA-encoding sequence that is harmful to cell therapy efficacy.
Regarding function, the claims recite that one RNA-encoding sequence will beneficial to cell therapy efficacy and the other sequence is harmful to cell therapy efficacy. However, the specification provides no description of any RNA-encoding sequences that are either beneficial or harmful to cell therapy efficacy, that would indicate possession at the time of filing. When discussing “beneficial” or “harmful” RNA-encoding sequences the specification teaches in Example 7, starting on pg. 71, that:
“The multimodal approach pursued here, like Castling, promotes the overexpression of beneficial ("good") miRNAs and inhibits the expression of harmful ("bad") miRNAs resulting in a simplified but efficient generation of CAR T cells harboring the desired miRNA modulation.”
The specification continues to teach on pg. 67 lines 9-18:
“Based on this expression profiling of miRNAs isolated from CAR-T cells exposed
to tumor cells, and in view of preliminary assays of miRNAs that are detrimental or beneficial to CAR-T cell efficacy, it is possible to categorize "bad" miRNAs as those having an at least 3-fold increase in expression in CAR-T cells exposed to tumor cells. Such miRNAs are assigned for KO. Similarly, it is possible to categorize "good" miRNAs as those having an at least 2-fold decrease in expression in CAR-T cells exposed to tumor cells or which have low (equal or below 100 RPM, reads per million as measured by transcriptome profiling using deep sequencing technology) and unchanged expression (equal to or less than a 1.5 fold change) when exposed to tumor cells. These miRNAs are assigned for KI.”
However, “good” and “bad” miRNA’s are relative, just as “harmful” and “beneficial” RNA-encoding sequences are relative (see 112b rejection below). Thus, the specification cannot be relied upon in teaching possession of “harmful” and “beneficial” RNA-encoding sequences since the specification’s examples are themselves relative.
The issue of written description regarding the claimed RNA-encoding sequences is further expanded by the art. For example, Ying et al. (2008, Mol. Biotechnol., Vol. 38, pgs. 257-268) teaches that:
“Because most of the miRNA suppresses gene function based on partial complementarity, conceivably one miRNA may target more than one mRNA, and many miRNAs may act on one mRNA, coordinately modulating the intensity of gene expression in various tissues and cells. Therefore, miRNAs may have a broad function in fine-tuning the protein-coding genes.” (pg. 260 col. 1 parag. 3 lines 1-7).
Thus, the nature of RNA-encoding sequences such as miRNA is that they can have more than one target, and this other target may be “beneficial” or “harmful” to cell therapy efficacy, which may be counter to the original target of the miRNA.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their structure. In the instant case, there are no RNA-encoding sequences described to indicate possession of a sequence that is either beneficial or harmful to cell therapy efficacy.
As of the filing date, there was no known or disclosed correlation between beneficial and harmful RNA-encoding sequences to cell therapy efficacy. There is no general knowledge in the art about regarding the activity of beneficial or harmful RNA-encoding sequences with respect to cell therapy efficacy to suggest that general similarity of structure confers the activity.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only characteristics described are in Table 2 with respect to being assigned “KO” or “KI” for miRNA and their expression in CAR-T cells that are exposed to tumor cells. The specification does not teach any other identifying characteristics such as domains relating to function/activity or any other related sequences that would guide the artisan to contemplate RNA-encoding sequences that would function as beneficial or harmful to cell therapy efficacy.
The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of a genus of beneficial and harmful RNA-encoding sequences at the time of filing.
Applicants' attention is directed to the decision in Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, which 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).
With the exception of the sequences referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed polynucleotides, and therefore conception is not achieve regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, none of the RNA-encoding sequences that are either beneficial or harmful to cell therapy efficacy meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In conclusion, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that applicant is in possession of the genus of RNA-encoding sequences that are either beneficial or harmful to cell therapy efficacy thereof as embraced by the claims.
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 1-14 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.
The term “harmful” in claim 1 is a relative term which renders the claim indefinite. The term “harmful” 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.
The specification does not provide a limiting definition for the term “harmful”, rather the specification refers to the harmful RNA-encoding sequences as “bad” miRNA’s (pg. 71 lines 27-30). Additionally, the specification teaches on pg. 3 lines 24-29:
“As a result of contact of a miRNA-expressing T-cell with the tumor and/or tumor environment and the myriad possible downstream effects, when "bad" miRNAs (harmful to the therapeutic effect of the T-cell) are upregulated and "good" miRNAs (beneficial to the therapeutic effect of the T-cell) are down-regulated, it results in dysfunctional T-cell states such as anergy, tolerance, and exhaustion.”
The specification continues to teach on pg. 67 lines 9-18:
“Based on this expression profiling of miRNAs isolated from CAR-T cells exposed
to tumor cells, and in view of preliminary assays of miRNAs that are detrimental or beneficial to CAR-T cell efficacy, it is possible to categorize "bad" miRNAs as those having an at least 3-fold increase in expression in CAR-T cells exposed to tumor cells. Such miRNAs are assigned for KO. Similarly, it is possible to categorize "good" miRNAs as those having an at least 2-fold decrease in expression in CAR-T cells exposed to tumor cells or which have low (equal or below 100 RPM, reads per million as measured by transcriptome profiling using deep sequencing technology) and unchanged expression (equal to or less than a 1.5 fold change) when exposed to tumor cells. These miRNAs are assigned for KI.”
However, it cannot be determined what is encompassed by a harmful RNA-encoding sequence as embraced by the claim since the specification only teaches that the harmful RNA-encoding sequences are bad for the therapeutic effect of the T-cell.
The term “beneficial” in claim 1 is a relative term which renders the claim indefinite. The term “harmful” 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.
The specification does not provide a limiting definition for the term “beneficial”, rather the specification refers to the beneficial RNA-encoding sequences as “good” miRNA’s (pg. 71 lines 27-30). Additionally, the specification teaches on pg. 3 lines 24-29:
“As a result of contact of a miRNA-expressing T-cell with the tumor and/or tumor environment and the myriad possible downstream effects, when "bad" miRNAs (harmful to the therapeutic effect of the T-cell) are upregulated and "good" miRNAs (beneficial to the therapeutic effect of the T-cell) are down-regulated, it results in dysfunctional T-cell states such as anergy, tolerance, and exhaustion.”
The specification continues to teach on pg. 67 lines 9-18:
“Based on this expression profiling of miRNAs isolated from CAR-T cells exposed
to tumor cells, and in view of preliminary assays of miRNAs that are detrimental or beneficial to CAR-T cell efficacy, it is possible to categorize "bad" miRNAs as those having an at least 3-fold increase in expression in CAR-T cells exposed to tumor cells. Such miRNAs are assigned for KO. Similarly, it is possible to categorize "good" miRNAs as those having an at least 2-fold decrease in expression in CAR-T cells exposed to tumor cells or which have low (equal or below 100 RPM, reads per million as measured by transcriptome profiling using deep sequencing technology) and unchanged expression (equal to or less than a 1.5 fold change) when exposed to tumor cells. These miRNAs are assigned for KI.”
However, it cannot be determined what is encompassed by a beneficial RNA-encoding sequence as embraced by the claim since the specification only teaches that the beneficial RNA-encoding sequences are good for the therapeutic effect of the T-cell.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
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