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 .
Response to Applicants’ Arguments and Amendments
A non-final was sent to applicants April 17, 2025. Then, applicants significantly amended the claims and added different types of inventions which had not been previously examined. Because the claims were so significantly altered and significantly differed from the previously examined claim set, the examiner conducted a second restriction which applicants then responded to. The claims have been changed from a method for differentiation and expansion to a clear treatment method. Because of the claim amendments, the former rejections are withdrawn and new rejections are put forward.
Restriction/Election
Applicant’s election without traverse of Group I (Claims 1-8,10-11), Species I (Genetically engineering the CD8+ T lymphocyte cells to secrete IL2 muteins, which signal through IL2Rβγ), Species II (SEQ ID: 6), Species III (1. Culturing said CD8+ T cells with soluble IL2 mutein), Species IV (an antibody that binds to IL2α), Species V (IL-7), Species VI (tumor draining lymph nodes), Species VII (express a CAR), Species VIII (alpha (CD25), Species IX (the inhibition of the interaction of the IL-2 receptor with its cognate protein occurs by downregulating the alpha subunit of the IL-2 receptor) in the reply filed on February 23, 2026 is acknowledged. Claims 16-23,25-30, and non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II-III and non-elected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 23, 2026.
Claim Objections
Claim 6 is objected to because of the following informalities: “cells culturing” should be –cell culturing--. Appropriate correction is required.
Oath
An appropriate oath needs to be provided by applicants.
Claim Rejections - 35 USC § 112
Enablement Rejection
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 1-8,10-11 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 enablement requirement. The claim contain 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 test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experiment to make and use the invention based on the content of the disclosure is undue.
Nature of the Invention:
The invention involves the administration of CD8+ T lymphocytes with a central memory phenotype to a subject for the treatment of cancer. The claims also recite that the CD8+ T lymphocytes experience signaling through the intermediate affinity IL-2 receptor (IL2rβγ), wherein said signaling is enhanced by culturing said CD8+ T lymphocytes with a soluble IL2 mutein or by genetically altering the genome of said CD8+ T lymphocytes prior to the expansion. A particular method/methods of administration are not specified.
Breath of the Claims:
The instant set of claims are so broad that they encompass any method of administration including placing CD8+ T lymphocytes in a foot cream that is then administered to feet. The claims also state that signaling through the intermediate affinity IL2 receptor can be enhanced by genetically altering the genome of the CD8+ T lymphocytes prior to expansion.
Teachings from the Prior Art:
June et al US 20150322169 teaches that T cells can be administered using: “aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The compositions described herein may be administered to a patient subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous (i.v.) injection, or intraperitoneally. In one embodiment, the T cell compositions of the present invention are administered to a patient by intradermal or subcutaneous injection. In another embodiment, the T cell compositions of the present invention are preferably administered by i.v. injection. The compositions of T cells may be injected directly into a tumor, lymph node, or site of infection (Paragraph 269 of June).”
Applicants Specification/Guidance/Working Examples
Example 8 of Applicants’ specification mentions that such cells can be administered by intravenous administration. The specification does not mention other methods of administration such as creams, intranasal sprays, oral tablets, etc.
The specification/Applicants’ PG Publication US 20220152107 mentions a few examples of genetic engineering. Paragraph 8 of PG Publication 20220152107 mentions that the lymphocytes can be engineered to express a T cell receptor (TCR) or a chimeric antigen receptor (CAR); however, this paragraph does not expressly state how this enhances signaling through the intermediate affinity IL2 receptor. Thus, it does not appear that TCRs or CARs alone can enhance signaling.
Furthermore, in regards to PG Publication US 20220152107, Paragraphs 26-29 provide more detailed examples of genetic engineering: genetically engineering the lymphoid cells to secrete a soluble protein, which block the IL2-IL2Rα interaction or, genetically engineering the lymphoid cells to decrease the expression of the IL2Rα receptor subunit (CD25) at the cell surface or, genetically engineering the lymphoid cells to increase the expression of the intermediate affinity IL-2 receptor at the cell surface. Paragraph 47 states, “genetically engineering the lymphoid cells to secrete IL2 muteins, which preferentially signals though the intermediate affinity IL2R.” These are the ways in which intermediate affinity binding can be enhanced through genetic engineering. No other examples are provided. These are the ways that the cells are genetically engineered so that they can be used as a successful therapy.
Conclusion: Applicants specification only mentions intravenous administration of the T cells with the central memory phenotype. It is unclear if other methods of administration taught in the prior art would work for T cells with the central memory phenotype in the treatment of cancer. Furthermore, the claims are only enabled for the following methods of genetic engineering: 1. genetically engineering T lymphoid cells to secrete a soluble protein which blocks the IL2-IL2Rα interaction, 2. genetically engineering the T lymphocyte to decrease the expression of IL2Rα receptor subunit (CD25) at the cell surface, 3. genetically engineering the T lymphoid cells to increase the expression of the intermediate affinity IL-2 receptor at the cell surface, and 4. genetically engineering the T lymphoid cells to secrete IL2 muteins that signal through the intermediate affinity IL2 receptors. Currently, the claims are also rejected under a 112(b) rejection, therefore, examiner is unable to state what is enabled.
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 1-8 and 10-11 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 instant claims recite an extraction step wherein CD8 T cells are harvested from a subject, a culturing step wherein signaling through an intermediate affinity IL-2 receptor is enhanced by culturing said CD8+ T lymphocytes with a soluble IL2 mutein or by genetically altering the genome of said CD8+T lymphocytes prior to the expansion step, an expansion step, a differentiation step following the expansion step. The claims do not clearly state at which point the T cells have a central memory phenotype; therefore, the process is unclear. The actual claim limitations of claim 1 do not even mention T cells with a central memory phenotype in any of the active method steps. Therefore, it is not clear what cell population is being administered to the subject. Because of such indefiniteness, the examiner cannot determine if the population is therapeutic or problematic (such as involving the administration of a non-homogenous population of cells).
Conclusion
All claims stand rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638