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 .
1. Formal Matters
A. In the response filed 9/16/26, Applicants elected SEB and IFN-g.
B. Claims 1-7, 9, 10, 18, 20, 22-25, 34-37 and 68 are pending and are the subject of this Office Action.
2. Claim Objections
A. Though not incorrect, it is noted that IFN uses the Greek symbol “g”, whereas TNF does not use the Greek symbol.
B. Claim 36 is objected to since “live cell” should be hyphenated.
3. Claim Rejections - 35 USC § 112(a) – written description
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.
A. Claim 34 is rejected under 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
This is a genus claim. The number of known cytokines is extensive (Holdsworth et al.) and the specification only provides adequate written description of IFN-g, IL-2, TNFa and IL-6. In addition, the Examiner was able to find GM-CSF as being released. However, other than these, neither the specification, claims, nor prior art provide written description of other cytokines or other molecules which are able to be measured in response to the method of the claim.
The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, IFN-g, IL-2, TNFa, IL-6 and GM-CSF are insufficient to describe the genus. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus. Thus, Applicant was not in possession of the claimed genus at the time the invention was made.
B. Claims 37 and 68 are rejected under 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
These are genus claims. Other than requiring a bispecific molecule that activates T cells and binds to immortalized cells, the specification and claims do not indicate what distinguishing attributes are shared by the members of the genus. Thus, the scope of the claims includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between/among genus members is permitted. The specification and claims do not provide any guidance as to what changes should be made. Structural features that could distinguish compounds in the genus from others in the nucleic acid, protein, or small organic molecule class are missing from the disclosure. No common structural attributes identify the members of the genus.
Qin (second paragraph of the Introduction) states –
So far, over 100 BsAbs are undergoing clinical research. Among these, thirteen BsAbs have been granted market approval, with nine targeting the CD3 receptor (Figs. 1 and 2, and Table 1). In the architecture of a T-cell redirecting BsAb, one arm is designed to bind to the tumor cell surface antigen tumor associated antigens (TAA), while the other arm is connected to the CD3ε subunit of the T cell receptor complex (TCR)
Therefore, it appears that, as late as 2024, after the instant filing date, at most, the bispecific antibodies that would fall into the instant genus would be those that target the CD3 receptor. It is unclear, however, how many were known at the time of the instant invention.
Other than this teaching by Qin and the instantly disclosed embodiment CD19-CD3 BiTE, the general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, CD19-CD3 BiTE, alone, or, at most, those binding CD3 that were known in the art at the time of the instant invention, are insufficient to describe the genus. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus. Thus, Applicant was not in possession of the claimed genus at the time the invention was made.
4. Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 1-6, 9, 20, 22-25 and 34 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Benson et al. (WO 2021/108455 – cited on the IDS filed 6/7/24).
The claims are essentially drawn to assessing potency of TILs by coculturing them with immortalized cells comprising a molecule that activates a T cell.
Regarding claims 1-6 and 9, Benson teaches that TILs can be activated by using a TCR agonist (e.g., a CD3 agonist, including OKT3; paragraph [007], [015], [028]). Paragraph [009] teaches that TILs can be cocultured with immortalized cells, including K562 ([015]). It is noted that paragraph [0099] of the published application teaches that K562 cells are immortalized cells that can be used in the instant claims. Genetically modified TILs are taught in paragraph [039].
Regarding claims 23 and 24, the K562 cells would meet these limitations, as they are a line of immortalized human cells.
Regarding claim 25, K562 cells can be engineered to express OKT3 ([0187]).
Regarding claim 34, TILs can be evaluated for IFNg release ([0235]).
5. Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A. Claims 7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Benson et al. in view of Chen et al. The teachings of Benson are seen above under 35 USC 102. Benson does not teach a membrane-bound OKT3 scFv. However, Chen teaches a membrane-tethered anti-CD3 scFv, which includes OKT3 (Abstract).
B. Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Benson et al. in view of Litton et al. The teachings of Benson are seen above under 35 USC 102. Benson does not teach bacterial superantigens. However, Litton teach that “[a]ntibody-targeted superantigen therapy induces tumor-infiltrating lymphocytes, excessive cytokine production, and apoptosis in human colon carcinoma” (Title).
C. Claims 35 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Benson et al. in view of Wei et al. (cited on the IDS filed 9/16/26). The teachings of Benson are seen above under 35 USC 102. Benson does not teach assessing the potency of TILs. However, Wei do teach the “[a]ssessment of the presence and potential of tumor-infiltrating lymphocytes in patients with acute myeloid leukemia” (Title). In addition, the “Purpose” of the research was to evaluate the anti-tumor activity of TILs against cancer (AML) cells. The fact that the TILs possessed anti-tumor activity indicates that one or more of “growth, cell death and/or viability of the immortalized cells” (instant claim 35) was observed. Lactase dehydrogenase was measured (see “Cell-mediated cytotoxic assay”).
D. Claims 37, 68 in view of either (1) Benson or (2) Benson in view of Wei, each in view of Hoffman and Gore. The teachings of Benson are seen above under 35 USC 102. Benson does not teach the use of bispecific molecules that activate T cells. However, Hoffman and Gore teach the “bispecific T-cell engaging or BiTE® antibodies), which directly recruit effector T cells to augment the anti-neoplastic effect” (Abstract; see also the Title). This is the same bispecific molecule described in the instant specification.
6. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
