DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's preliminary amendment filed on 01/30/2025 is acknowledged.
Claims 1-4, 13, 17, 20, 29, 38-42, 46-48, 50, 52-53 and 71 are pending.
3. Claim 13 is objected to because the abbreviations “MBOP,” “AO,” and “DOTA” are not accompanied by the terms they represent. While it may be possible to find the relevant terms in the specification, the onus of doing so should not be placed on those seeking to determine the scope of the claims. Where possible, claims are to be complete in themselves.
4. 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.
5. Claims 1-4, 13, 17, 20, 29, 38-42, 46-48, 50, 52-53 and 71 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claims 1 and 17 are indefinite in the recitation of domains “derived from” the respective reference molecules, because neither the nature nor the degree of acceptable “derivation” is defined.
(ii) Claims 4, 13,20, and 29 are indefinite in recitations of a signal peptide, an scFv, a transmembrane domain, and an intracellular domain, respectively, which “has” the recited nucleic acid sequence. It appears that the intended meaning was “is encoded by” the recited nucleic acid sequence, which interpretation is provisionally assumed for examination purposes.
(iii) Claim 50 is indefinite in the recitation of “T cells that encode a chimeric antigen receptor.” It appears that the intended meaning was “T cells comprising a nucleic acid encoding a chimeric antigen receptor,” which interpretation is provisionally assumed for examination purposes.
(iv) Claim 50 is further indefinite in the recitation of “binary activated” T cells and NK cells, because the meaning of the term is unknown.
(v) Claim 53 is indefinite because of an inconsistency between the recited “memory, cytotoxic, and regulatory phenotypes,” which are characteristic on T cells, and the generic “immune cell” recited in claim 39 on which claim 53 depends.
(vi) Claim 53 is further indefinite in the recitation of the phrase “a change in phenotype of the immune cells selected from the group consisting of memory, cytotoxic, and regulatory phenotypes,” because (a) it is unknown whether the phenotype changes “to” or “from” memory, cytotoxic, or regulatory, and (b) the phenotype to or from which the change occurs is not defined.
(vii) Claim 71 is indefinite in the recitation of a method for treating “a disease or disorder,” because the subject population is not defined.
(viii) Claim 71 is further indefinite because of the inconsistency between the preamble of the method, “a method for treating a disease or disorder,” and the resolution step, “thereby stimulating the immune cells in the composition.”
(ix) Claims 2-4, 13, 17, 20, 29, 38-42, 46-48, 50, 52-53 and 71 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
6. 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.
7. Claim 71 is rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contain(s) subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not provide a sufficient enabling description of a method for treating a disease or disorder comprising administering an immune cell containing a nucleic acid encoding a cytokine receptor switch as recited in claim 1, and a synthetic small molecule conjugated to a carrier.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
The claim is directed to a method for treating any disease or disorder, comprising administering any immune cell containing a nucleic acid encoding a cytokine receptor switch, and any synthetic small molecule conjugated to a carrier, wherein the cytokine receptor switch comprises an scFv that specifically binds any synthetic, substantially nonimmunogenic small molecule, and an intracellular domain of any cytokine receptor.
The specification describes in Example 1 working examples wherein T cells comprising nucleic acids encoding cytokine receptor switches based on IL-2RA, IL- 2RB, IL-2RG, IL-7RA, IL-15RA, or IL-21R were stimulated on FITC-conjugated-BSA-coated plate in the presence or absence of CD3/CD28 co-stimulation for up to 2 weeks. The results indicate that some of the tested cytokine receptor switches increased effector and/or central memory markers with CD3/CD28-costimulation, and IL7RA-cytokine receptor switch increased central memory markers on CD4.sup.+ T cells without CD3/CD28-costimulation under these conditions. The specification further describes in Example 3 working examples wherein NK92 cells expressing different combinations of cytokine receptor switches were stimulated on FITC-conjugated-BSA-coated plate for up to 7 days. The results indicate that certain cytokine receptor switch combinations promoted cell proliferation and increased expression of an activation marker under these conditions.
Treating a disease or disorder requires that positive clinical outcomes be achieved as a result of administering the treatment with sufficient predictability. The claim does not specify any relationships between the identity of the cytokine receptor on which the therapy is based, the specificity of the scFv component, the identity of the synthetic small molecule, and the nature of disease or disorder being treated. The disclosure does not appear to provide any guidance, direction, or working examples relevant to the claimed method as recited. Accordingly, the entire scope of experimentation required to develop methods of treatment as recited is left to those skilled in the art, the present claims and disclosure amounting to nothing more than an invitation to the skilled artisan to invent such methods.
8. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
9. Claims 1-4, 17, 20, 29, 38-42, 46-48, 50, 52-53 and 71 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Irvine et al. (US 20200345853), and claim 13 is rejected as being anticipated by Irvine et al. as evidenced by Novina et al. (US 20190256597).
Irvine teaches chimeric cytokine receptors comprising a signal peptide, an anti-FITC scFv, a hinge domain, a transmembrane domain, and an intracellular cytokine receptor domain (e.g. [0029], [0030], [0130], [0223]), which are within the scope of at least instant claim 1.
Signal peptides can be derived from any protein that has an extracellular domain or is secreted, and may include any signal peptides known in the art (e.g. [0219]).
The scFv is specific to FITC (fluorescein), exemplified by anti-FITC scFv 4m5.3 (e.g. [0030], [0033], [0176], [0177], [0324], [0327]).
The hinge domain of the chimeric cytokine receptor is derived from CD8 (e.g. [0231], [0244]).
The transmembrane domain of the chimeric cytokine receptor is native to IL2R beta [IL-2RB], IL2R gamma [IL-2RG], or IL-7RA (e.g. [0231], [0244]).
The intracellular domain of the chimeric cytokine receptor is native to IL- 2RB, IL-2RG, IL-4R, IL-7RA, IL-9R, IL-15RA or IL-21R (e.g. [0032], [0234]).
The chimeric cytokine receptor is expressed in an immune cell, such as a T cell or an NK cell, wherein the T cell is CD4+ or CD8+ (e.g. [0026], [0084], [0124]), and wherein the immune cell is activated upon binding of the chimeric cytokine receptor to its ligand (e.g. [0022]-[0026]).
Irvine teaches expressing two different chimeric cytokine receptors, or a chimeric cytokine receptor and a CAR, in an immune cell which is administered to a patient (e.g. [0328]). For that purpose, Irvine exemplifies a pair of chimeric cytokine receptors, one including a target-binding domain including an anti-FITC scFv and an IL-2Rβ intracellular cytokine receptor domain, the second including a target-binding domain including avidin and a common γ chain intracellular cytokine receptor domain [IL-2RG] (e.g. [0327]).
Accordingly, Irvine explicitly teaches all of the limitations of claims 1-3, 17, 38-42, 46-48, 50, 52-53, and 71.
Claim 13 is anticipated by Irvine’s teachings of anti-FITC scFv 4m5.3 [0324], because instant SEQ ID NO 52 is identical to SEQ ID NO: 3 of Novina et al. (US 20190256597) (see SCORE), which is the amino acid sequence of anti-FITC scFv 4m5.3, as disclosed in Example 7 of Novina at [0290].
Claim 4 is included in the rejection, because it was routine in the art to construct fusion proteins with a signal peptide native to the main domains of the fusion protein. Therefore, a skilled artisan would at once envisage an IL-2RB signal peptide as part of chimeric cytokine receptor comprising IL-2RB transmembrane domain and IL-2RB intracellular domain, as taught by Irvine (e.g. [0032], [0231], [0234], [0244]). Claim 4 is anticipated, because the recited SEO ID NO: 4 is the amino acid sequence of IL-2RB signal peptide, and as such is inherent in IL-2RB signal peptide.
Likewise, claims 20 and 29 are anticipated, because the recited SEO ID NOS: 20 and 36 are the amino acid sequences of IL-2RB transmembrane and intracellular domain, respectively, and as such is inherent in Irvine’s teachings of IL-2RB transmembrane and intracellular domains (e.g. [0032], [0231], [0234], [0244]).
10. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
11. Claims 1-4, 13, 20, 29, 38-39, 52-53 and 71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending application USSN 19229839, published as US 20250297220.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of USSN ‘839.
The latter recite an immune cell expressing an engineered cytokine receptor switch comprising an scFv, a transmembrane domain, and a cytokine receptor intracellular domain (claims 218-220), wherein the scFv binds fluorescein or tetraxetan [DOTA] (claims 224-225), and a method comprising administering the immune cell to a cancer patient (claims 236-237).
A signal peptide is required for expression of transmembrane polypeptides, as a person of skill in the art would be aware, and as such would be at once envisaged by a skilled artisan. It was routine in the art before the effective filing date of the claimed invention to optimize binding of chimeric receptors to their targets by providing a hinge domain between the scFv and the transmembrane domain, and therefore a hinge domain would be at once envisaged by a person of skill in the art.
USSN ‘839 further recites intracellular domain comprising one of SEQ ID NOS: 29-34 (claim 221), which are the sequences of intracellular domains of IL-2RA, IL- 2RB, IL-2RG, IL-7RA, IL-15RA and IL-21R, respectively (Table 3 of US 20250297220), and are identical to instant SEQ ID NOS: 34, 36, 38, 42, 46 and 48, respectively.
USSN ‘839 further recites transmembrane domain comprising one of SEQ ID NOS: 23-28 (claim 222), which are the sequences of transmembrane domains of IL-2RA, IL- 2RB, IL-2RG, IL-7RA, IL-15RA and IL-21R, respectively (Table 4 of US 20250297220), and are identical to instant SEQ ID NOS: 18, 20, 22, 26, 30 and 32, respectively.
USSN ‘839 further recites cytokine receptor switch comprising SEQ ID NO: 1 (claim 234), which comprises instant SEQ ID NO: 52 (see SCORE).
Claim 4 is included in the rejection for the same reasons as articulated in section 9 above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. Claims 1-4, 13, 17, 20, 29, 38-39, 46 and 52-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending application USSN 19229806, published as US 20250297022.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of USSN ‘806.
The latter recite an immune cell expressing an engineered cytokine receptor switch comprising a signal peptide, an scFv, a hinge domain, a transmembrane domain, and a cytokine receptor intracellular domain (claims 216 and 227), wherein the scFv binds fluorescein or DOTA (claim 229).
Intracellular domain is exemplified as SEQ ID NO: 29, native to IL-2RA (claims 217-218), identical to instant SEQ ID NO: 34.
Transmembrane domain is exemplified as SEQ ID NO: 23, native to IL-2RA (claims 221-222), identical to instant SEQ ID NO: 34.
Hinge domain is exemplified as SEQ ID NO: 22, native to CD8 (claims 223-224).
Signal peptide is exemplified as SEQ ID NO: 15, native to IL-2RA (claims 225-226), identical to instant SEQ ID NO: 2.
The scFv is exemplified as SEQ ID NO: 21 (claim 228), identical to instant SEQ ID NO: 52 (see SCORE).
When the scFv binds its target, the intracellular domain activates cytokine signaling pathway which causes conversion of the immune cell to memory phenotype (claims 230-232).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
13. The following prior art references, which teach various aspects of the claimed invention, are cited of record but not presently relied upon:
US 20190292533
US 20220214330
US 20230183351
US 20230348556
US 20230149465
US 20180142034
14. Conclusion: no claim is allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
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