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 .
DETAILED ACTION
1. Applicant’s amendment and response filed 6/9/26 is acknowledged and has been entered. Amended claims 1 and 3 and newly added claims 13-15 are presently being examined. Claim 1 is an independent claim.
2. The terminal disclaimer filed on 6/9/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11,633,428 or US Patent No. 11,633,429 has been reviewed and is accepted. The terminal disclaimer has been recorded. Accordingly, the double patenting rejections of record in the last office action based upon these said patents have hereby been withdrawn.
3. Claim interpretation: The specification discloses at [0087] that pharmaceutical compositions and formulations can be prepared by mixing the active ingredients with one or more optional pharmaceutically acceptable carriers in the form of lyophilized formulations or aqueous solutions, and that these carriers are generally nontoxic to recipients at the dosages and concentrations employed. With regard to “pharmaceutical composition” recited in the instant claims, the term “pharmaceutical” must be weighed with the structural limitations of the claim. If the composition merely comprises a known composition, the term carries little weight absent evidence of structural difference.
The specification discloses at [0030] that as used herein a “disruption” or “alteration” of a gene refers to the elimination or reduction of expression of one or more gene products encoded by the subject gene in a cell as compared to the level of expression of gene product in the absence of the alternation, with exemplary gene products including mRNA and protein products encoded by the gene. The alteration may be transient or reversible, and in other cases, permanent. In some embodiments, gene activity or function, as opposed to expression is disruption, with exemplary methods including gene silencing, knockdown, knockout, and/or gene alteration techniques such as gene editing.
4. 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.
5. Claims 1, 3 and 13-15 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 written description rejection.
This is a new ground of rejection necessitated by Applicant’s amendment filed 6/9/26. Applicant has canceled claims 2 and 4-12 and has amended instant base claim 1 to recite that the cells are CD4+CD25+ Tregs that comprise disrupted expression of SRC-3 and one or more CRISPR reagents that target SRC-3.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.' " Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP 2163 I.A.
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." See MPEP 2163 II.3.
Applicant has broadly claimed:
A pharmaceutical composition comprising engineered CD4+CD25+ Tregs comprising:
(a) disrupted expression of SRC-3, and (b) one or more CRISPR reagents that target SRC-e (as is recited in instant base claim 1);
The pharmaceutical composition of claim 1, wherein the engineered CD4+CD25+ Tregs are FoxP3+ (as is recited in dependent claim 3);
The pharmaceutical composition of claim 1, wherein the engineered CD4+CD25+ Tregs are autologous or allogenic with respect to a subject (as is recited in claim 13);
The pharmaceutical composition of claim 1, wherein the one or more CRSPR reagents comprise one or more guide RNAs and a CAS9 enzyme (as is recited in claim 14); and
The pharmaceutical composition of claim 1, further comprising pharmaceutically acceptable excipients (as is recited in claim 15).
As such, the pharmaceutical composition comprises CD4+CD25+ Treg cells comprising:
a) (any) disrupted expression of SRC-3, and b) (any) one or more CRISPR reagents that target SRC-3, wherein the one or more agents in claims 1, 3, 13 and 15 are generically recited but have the functional property of disrupting expression of SRC-3 in the Treg cells, or wherein in claim 14 they are recited as subgenera of one or more CRISPR reagents that target SRC-3 that comprise one or more guide RNAs and a Cas9 enzyme (i.e., the Tregs are exposed ex vivo to an effective amount of one or more agents that target SRC-3) to disrupt expression of SRC-3 (e.g., [0015]) in order to create the said pharmaceutical composition.
The specification does not disclose a representative number of species of one or more agents that target SRC-3, nor sufficient relevant identifying characteristics in the form of structure or functional characteristics coupled with a known or disclosed correlation between structure and function, nor the Tregs that comprise them.
The specification discloses that in specific embodiments, the agent that targets endogenous SRC-3 may be nucleic acid CRISPER reagents ([0015]) such as RNA-guided nucleases such as a CRISPR-associated nuclease (Cas) that can be specifically designed to be targeted to the sequence of the SRC-3 gene or a portion thereof ([0044]).
The specification discloses at [0030] that as used herein a “disruption” or “alteration” of a gene refers to the elimination or reduction of expression of one or more gene products encoded by the subject gene in a cell as compared to the level of expression of gene product in the absence of the disruption or alteration, with exemplary gene products including mRNA and protein products encoded by the gene. The alteration may be transient or reversible, and in other cases, permanent. In some embodiments, gene activity or function, as opposed to expression is disrupted, with exemplary methods including gene silencing, knockdown, knockout, and/or gene alteration techniques such as gene editing. The specification discloses that the altered gene expression is carried out by effecting a disruption in the gene, such as a knock-out, insertion, missense or frameshift mutation such as biallelic frameshift mutation, deletion of all or part of the gene such as one or more exons or portions therefore, and/or knock-in. In some embodiments, the altered gene expression can be effected by sequence-specific or targeted nucleases, including DNA-binding targeted nucleases such as CRISPER-associated nuclease (Cas), specifically designed to be targeted to the sequence of the SRC-3 gene or a portion thereof ([0044], [0052]-[0066]). The specification discloses that the target sequence for SRC-3 may comprise any polynucleotide and the target sequence may be located in the nucleus or cytoplasm of the cell ([0067]).
There is no evidence of record for a representative number of species of such agents that target the disruption of SRC-3 either in the specification or the art, nor a structure function relationship therefore.
Evidentiary reference Synthego (2026, Chapter 01: 1-8) teaches that the guide RNA should be specific for only the target DNA sequence and not anywhere else in the genome, the design of which must be experimentally verified and/or predicted using sophisticated computational biology tools. In addition, critical parameters for gRNA design for knockouts must be ascertained as the location target DNA range for guide RNA is quite narrow. Synthego teaches that multiple gRNAs targeting the same gene has been shown to improve editing efficiently, increasing the chance of generating a knockout. Although Synthego teaches a proprietary CRISPR design tool, experimentation still must be engaged in to design and test one or more CRISPR reagents that have the functional property of targeting disruption of SRC-3, and particularly considering that the definition of disruption of SRC-3 in the instant specification is much broader than just knocking out SRC-3, as is enunciated above. See entire reference.
The specification discloses and the art evidences that the identities of the sequences of the nucleic acid or amino acid molecule inhibitors (i.e., the one or more CRISPR reagents that target SRC-3 and have the functional property of disrupting expression of SRC-3) cannot be envisioned a priori. Experimentation must be engaged in to determine their identities.
There is also no evidence for a representative number of species of such agents having the requisite functional property, as the genus of such agents are structurally diverse, including wherein they are sequences. In addition, as there are potentially many CRISPR nucleic acid disruptors of SRC-3 that produce Tregs having different genetic disruptions, and the identities of these cells cannot be envisioned a priori, and there is no evidence of record for a representative number of such Tregs.
The specification teaches a genetically engineered mouse model where SRC-3 was specifically deleted in Foxp3-expressing Treg cells by treatment of the mice with tamoxifen, resulting in activation of Cre and excision of exons 11 and 12 of the SRC-3 gene (not by CRISPR-mediated knockout) ([0021]).
The specification also discloses at Example 3 that an enriched and expanded population of CD4+ cells from mice were subjected to nucleofection with a Cas9-NCoA3 guide RNA ribonucleoptorein using a nucleofection kit, but does not disclose the identity of the guide RNA. The said example discusses disrupted expression in terms of ablating SRC-3 ex vivo in T cells obtained from mice using CRISPR-based gene targeting ([0117]), i.e., this example discusses completely removing, silencing or destroying the function of the gene (and not including knocking it down). Recall that the specification discloses at [0030] that as used herein a “disruption” or “alteration” of a gene refers to the elimination or reduction of expression of one or more gene products encoded by the subject gene in a cell as compared to the level of expression of gene product in the absence of the disruption or alteration, with exemplary gene products including mRNA and protein products encoded by the gene. However, even if the specification were to have provided for reduction of expression, this one species in itself would not provide adequate written description for the genus of one or more CRISPR reagents that target SRC-3 and the Tregs that comprise a disruption in SRC-3, including in view of Treg cells from different species of animals/mammals and including in view of the broad definition in the instant specification for “disrupted expression of SRC-3”.
Therefore, it appears that the instant specification does not adequately disclose the breadth of the immune cell and the agent having the functional property of targeting SRC-3 or that targets the disruption of SRC-3 recited in the instant composition claims. In light of this, a skilled artisan would reasonably conclude that Applicant was not in possession of the genus of all such immune cells and agents at the time the instant application was filed.
Applicant has argued in the amendment and response filed 6/9/26 (at section “II”) that because the originally filed disclosure provides support for the present claim amendment for one or more CRISPR reagents that target SRC-3, the written description requirement is satisfied. Applicant points to paragraph [0111] and [0113], alleging that they provide detailed experimental protocols to obtain the pharmaceutical composition recited by presently amended claim 1.
However, Applicant’s arguments are not persuasive for the reasons enunciated in the instant rejection.
6. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 6, 8 and 12 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.
Applicant has canceled claims 6, 8 and 12.
7. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10 and 12 under 35 U.S.C. 102(a)(i) as being anticipated by Xu et al. (PNAS, 2000, 97(12): 6379-6384, IDS reference).
Applicant has canceled claims 10 and 12
8. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10 and 12 under 35 U.S.C. 102(a)(i) as being anticipated by Song et al. (PNAS, 2016, 113(18): 4970-4975, IDS reference).
Applicant has canceled claims 10 and 12
9. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10 and 12 under 35 U.S.C. 102(a)(i) as being anticipated by Wang et al. (Mol. Endocrinol. 2011, 25(12): 2041-2053, IDS reference).
Applicant has canceled claims 10 and 12.
10. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 1-3 under 35 U.S.C. 102(a)(i) as being anticipated by Tanaka et al. (Cell Reports 5/22/2018, 23: 2318-2329, IDS reference) as evidenced by Singer, Bernhard. (2013, Re: How does culture with anti-CD3/anti-CD28 mAb alone compare to culture with anti-CD3/anti-CD28 mAb and subsequent treatment with PMA/Ionomycin?. Retrieved from: https://www.researchgate.net/post/How-does-culture-with-anti-CD3-anti-CD28-mAb-alone-compare-to-culture-with-anti-CD3-anti-CD28-mAb-and-subsequent-treatment-with-PMA-Ionomycine/51812f7ccf57d7a07600002a/citation/download, one page) and Tran et al. (Blood, 2007, 110: 2983-2990).
Applicant has amended the claims to recite that the Treg cells comprise disrupted expression of SRC-3 and one or more CRISPR reagents that target SRC-3, limitations that the art reference does not teach.
11. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10-12 under 35 U.S.C. 102(a)(i) as being anticipated by
WO2015164818 A1.
Applicant has canceled claims 10-12.
12. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10-12 under 35 U.S.C. 102(a)(i) as being anticipated by
US 9,683,237.
Applicant has canceled claims 10-12.
13. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10-12 under 35 U.S.C. 102(a)(i) as being anticipated by US 9,683,237.
Applicant has canceled claims 10-12.
14. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10 and 12 under 35 U.S.C. 103 as being unpatentable over Eedunuri et al. (Mol. Endocrinol. 2015, 29(8): 1170-1183, IDS reference).
Applicant has canceled claims 10 and 12.
15. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 1-3 as being unpatentable over Tanaka et al. (Cell Reports 5/22/2018, 23: 2318-2329, IDS reference) in view of Tran et al. (Blood, 2007, 110: 2983-2990), and as evidenced by Singer, Bernhard. (2013).
Applicant has amended the claims to recite that the Treg cells comprise disrupted expression of SRC-3 and one or more CRISPR reagents that target SRC-3, limitations that the art references do not teach.
16. Applicant’s amendment filed 6/9/26 has overcome the prior rejection of record of claims 10-12 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,497,772.
Applicant has canceled claims 10-12.
17. Applicant’s amendment filed 6/9/2026 has overcome the prior rejection of record of claims 10-12 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 9,683,237 (IDS reference) in view of WO2015164818 A1.
Applicant has canceled claims 10-12.
18. No claim is allowed.
19. 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.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights