CTNF 17/814,211 CTNF 80625 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 Status of Application/Amendment/Claims Applicant's response filed 03/10/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 09/10/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. With entry of the amendment filed on 08/21/2025, claims 1, 3-6, 10-22, 25 and 36 are pending. After further consideration, claim 12 has been rejoined. Claims 1, 3-6, 10-12, 16-22, 25 and 36 are currently under examination. Claims 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The 103 and Double Patenting Rejections are withdrawn in view of the new rejections herein. New Claim Rejections Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. Claims 1, 3-6, 10-12, 16-22, 25 and 36 is/are rejected under 35 U.S.C. 103 as being as being obvious over Radovic-Moreno et al. (WO 2015/187966), Mortensen et al. ("Next generation adoptive immunotherapy—human T cells as carriers of therapeutic nanoparticles." Journal of nanoscience and nanotechnology 7.12 (2007): 4575-4580), Wang et al. ("Purification of a human prostate specific antigen." The Journal of urology 167.2 (2002): 960-964 see entire reference cited on 892 mailed 06/17/2024) and Banga et al. (J. Am. Chem. Soc. 2014 9866-9869). Regarding Claim 1, 3, 5 and 6, Radovic-Moreno discloses a composition comprising a pharmaceutically acceptable carrier (pg. 33, In 25-30) having a spherical nucleic acid (SNA) nanostructure (pg. 2, In 19-20), the SNA comprises a nanoparticle (pg. 2, Iine 20-21), an oligonucleotide on the surface of the nanoparticle (pg. 2, Iine 22-23), and an antigen (pg. 7, Iine 7-16). Radovic-Moreno discloses the nanoparticle includes a liposome core (pg 14, lines 21-30) and teach the oligonucleotide is linked with a tocopherol (page 5, lines 11). Radovic-Moreno discloses the oligonucleotide comprises a sequence that is a TLR9 agonist or a CpG (see pages 3-5, bottom 24-25). Radovic-Moreno discloses SNA are useful for mediating immune stimulatory effects for treatment of cancer and can be used as a vaccine (pg 35 line 28-30) and teach the nanostructure can be delivered to a subject via in-vivo or ex-vivo administration for therapeutic use (pg 33 line 20). Radovic-Moreno does not specifically disclose a composition comprising a carrier and a SNA or methods of administering the nanostructure to a cell for ex-vivo use to treat a subject, however the broadest reasonable interpretation of the teachings of Radovic-Moreno are interpreted to mean the SNA nanoparticle (nanostructure) can be administered to a cell ex vivo wherein the cell is administered to subject for therapeutic use as an active agent. As evidenced by Naldini, Luigi. ("Ex vivo gene transfer and correction for cell-based therapies." Nature Reviews Genetics 12.5 (2011): 301-315), this interpretation is in line with the meaning of ex-vivo treatment. Naldini teach Ex vivo cell therapies are based on the ability to isolate stem, progenitor or differentiated cells from a patient or a normal donor, expand them ex vivo — with or without genetic modification — and administer them to the patient (see page 301 first para.). The prior art teach it is well known that therapeutic nanoparticles can be transfected into T-cells for adoptive cell immunotherapy in treatment of diseases such as cancer (see page 4575-4576 and Fig. 1 of Mortensen et al.). Mortensen et al. teach incubating other types of nanoparticles with a tumor specific T cells can provide the T cell with new properties (see page 4575). Mortensen et al. teach the main advantage of upgrading the T cell by including a payload is that the T cell is helped by the nanoparticle to kill a cell such as a cancer cell (see page 4575). Mortensen et al. also teach cells comprising nanoparticles can proliferate and those daughter cells comprise the nanoparticle (see 4577-4578). One of skill in the art would have used the SNA nanoparticle for adoptive cell immunotherapy as taught by Mortensen et al. to deliver of the cell ex-vivo as a therapeutic agent wherein the cell has new advantages properties. It would have been obvious to one of ordinary skill in the art to use a composition comprising a pharmaceutical carrier and a SNA nanoparticle in ex-vivo methods to treat cancer particularly given nanoparticles can be transferred into T-cells that gain new therapeutic properties to target cancer cells as taught by Mortensen et al. Regarding claims 10-11, Radovic-Moreno disclose the nanoparticle can comprise additional oligonucleotides in addition to the oligonucleotide attached to the nanoparticle (see page 18 lines 3-12). Regarding claims 18, 19, 21, 22, 35 and 36, Radovic-Moreno discloses the liposome core can have up to 1000 oligonucleotides on the surface (page 17 lines 20-25), teach the antigen can be encapsulated or on the surface of the nanoparticle (see page 29 line 24-30) and can be a cancer antigen (page 31), which meets the limitations of claim 1 of a “tumor-associated antigen”. Radovic-Moreno does not disclose the cancer antigen is associated with any specific cancer as in claim 36, however Radovic-Moreno disclosed the cancer antigen can be prepared from cancer cells and thus it would have been obvious to make the prostate cancer antigen from prostate cancer cells (see page 31 line 4-13), the methods of which are taught by Wang et al. (see entire reference). This meets the limitation of claim 36. Regarding claim 25, Radovic-Moreno disclose the nanostructures can be delivered in an appropriate adjuvant to provoke an immune response as in a vaccine (see page 33 line 25 to page 34 lines 1-30) and it would have been obvious to use the composition comprising the cell as a vaccine. Regarding claims 4, 12, 16 and 17, Banga discloses a composition comprising a liposomal spherical nucleic acid (SNA) and a Tocopherol-modified DNA , wherein the lipid is DOPC (see Scheme 1 and pages 9866-9867) and wherein the oligonucleotide is an antisense that effectively knockdown expression (see page 9866 col. 2). Banga et al. teach the nanoparticle is less than 50 nanometers (see 9866 second column) and it would have been obvious to use a lipid such as DOPC given Banga et al. teach this architecture stabilized the construct and facilitates cellular internalization and use an antisense as the oligonucleotide (see abstract). Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed. Claim Rejections - 35 USC § 112 07-30-01 AIA The following is a quotation 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 35 U.S.C. 112 (pre-AIA), first paragraph: 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. Written Description 07-31-01 AIA Claim s 1, 3-6, 10-12, 16-22, 25 and 36 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated: To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood , 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co. , 43 USPQ2d 1398. The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc ., 935 F.2d at 1563-64, 19 USPQ2d at 1117. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species 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 functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The claims are drawn to a genus of cells comprising a pharmaceutically acceptable carrier and a spherical nucleic acid (SNA) comprising a nanoparticle, an CpG nucleotide and any tumor-associated antigen with the function of becoming an active agent due to entry into any cell. The specification describes the activity of the agents as performing multiple functions in an immunotherapeutic mode of action such as transfer of SNA and components to other cells and direct attack of target cells (0007). When determining 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 complete structure. In the instant case, the specification describes in Example 1, administration of T chaperones (T-cells exposed to SNA) i.v. to tumors in mice which resulted in the ability to induce T cell priming in vivo, the ability to retain long term killing functions and the ability to induce T chaperone exosomal antigen transfer for bystander priming (pages 24-25). The specification does not describe all the broad immunotherapeutic functions claimed when the SNA is administered to any cell type and therefore this example does not encompass the vast number of different cells types and immunological functions that can occur in a cell or subject. It is then 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 genera. In the instant case, the only other identifying characteristics are methods of inducing T cell priming, antigen transfer and T-cell killing functions. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination. Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant a vast number of cells having any number of immunotherapeutic functions after being contacted with a SNA, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed. "A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) ( emphasis added ). Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin , 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester , 358 F.3d at 927, 69 USPQ2d at 1895. 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). The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618. Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every variation of different cells having a SNA nanoparticle with the function of becoming an active agent performing multiple functions in an immunotherapeutic mode of action. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder , 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the compositions comprising an acceptable carrier and a cell having a SNA and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention. Response to Arguments Applicant’s argument is persuasive against Beduneau et al. and thus arguments against the previous 103 will not be addressed. Applicant then argues unexpected results wherein the specification demonstrates unexpected results using two different tumor models with different model antigens (B16/gp100 and LLC1-OVA/OVA-I), demonstrating that the effect is not limited to a particular antigen. The specification at paragraph [0007] states that "[t]hese SNA-loaded cells perform multiple functions in an immunotherapeutic mode of action. Among the demonstrated activities of these cells, once re-introduced to animal models, are 1) the transfer of SNA and SNA components (adjuvant polynucleotides (e.g., a CpG oligonucleotide), antigens) to other cells (such as an antigen presenting cell (APC)); and 2) direct attack of target cells." See, e.g., paragraph [0007] of the application as filed. A skilled artisan could ascertain from this data a trend that would allow reasonable extension of the probative value to the full scope of the claims. Importantly, these unexpected results are supported by experimental data in the specification (Examples 1, Figures 5-8), not mere attorney argument . In response, given the interpretation of Radovic-Moreno who teach methods of administering the nanostructure to a cell for ex-vivo use to treat a subject and the prior art teachings of Mortensen et al. who make it obvious to use the method of ex-vivo use of the SNA for adoptive cell therapy, the results of the cell becoming an active agent are not unexpected with respect to the breadth of the definition of an active agent. Mortensen et al. teach incubating other types of nanoparticles with a tumor specific T cells can provide the T cell with new advantageous properties. With respect to the demonstrated activities of these cells, once re-introduced to animal models, are 1) the transfer of SNA and SNA components (adjuvant polynucleotides (e.g., a CpG oligonucleotide), antigens) to other cells (such as an antigen presenting cell (APC)); and 2) direct attack of target cells, MPEP 716.02(c) states “Evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978)” and “Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977)”. Applicant’s claim that the invention demonstrates unexpected results does not shown a significance equal to or greater than the expected properties of upgrading a T cell with the nanoparticle because Mortensen et al. teach this step can destroy and attack the target cancer cells and thus one would expect the claimed invention to have the same effect on cancer cells when T-cells are contacted with a SNA are useful for mediating immune stimulatory effects for treatment of cancer as taught by of Radovic-Moreno. MPEP 716.02(c) also states "Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). Thus the claimed unexpected results of immune functions, direct attack of target cells and transfer of SNA nanoparticle to other cells is an expected benefit of upgrading a T cell with a therapeutic nanoparticle, as taught by Mortensen et al. It was known in the prior art that nanoparticles can be transfected into T cells which provides the T cells with new properties and it would have been obvious to expose T cells to SNA for treatment of cancer ex-vivo as described by Radovic-Moreno. The unexpected properties of the claimed invention are not shown to have a significance equal to or greater than the expected properties and the expected beneficial results are evidence of obviousness. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111 . The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm. If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199. /KIMBERLY CHONG/ Primary Examiner Art Unit 1636 Application/Control Number: 17/814,211 Page 2 Art Unit: 1636 Application/Control Number: 17/814,211 Page 3 Art Unit: 1636 Application/Control Number: 17/814,211 Page 4 Art Unit: 1636 Application/Control Number: 17/814,211 Page 5 Art Unit: 1636 Application/Control Number: 17/814,211 Page 6 Art Unit: 1636 Application/Control Number: 17/814,211 Page 7 Art Unit: 1636 Application/Control Number: 17/814,211 Page 8 Art Unit: 1636 Application/Control Number: 17/814,211 Page 9 Art Unit: 1636 Application/Control Number: 17/814,211 Page 10 Art Unit: 1636 Application/Control Number: 17/814,211 Page 11 Art Unit: 1636 Application/Control Number: 17/814,211 Page 12 Art Unit: 1636 Application/Control Number: 17/814,211 Page 13 Art Unit: 1636 Application/Control Number: 17/814,211 Page 14 Art Unit: 1636
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