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 .
Restrictions/Elections
Applicant’s election of the following invention/species without traverse, as set forth in the Reply filed 13 August 2025, is acknowledged:
Applicant elects Group I, encompassing claims 22-25 and 27-49.
Applicant further elects (a) the method does NOT further comprise measuring levels of MDSCs from a blood sample collected from the subject, (b) a PD-1 antibody as an immune checkpoint inhibitor, and (c) radiation therapy as an additional therapy.
Claims 22-25 and 30-49 read on elected Group I and the elected species.
Status of the Claims
Claims 22-49 are currently pending. Claims 26-29 are withdrawn. Claims 22-25 and 30-49 are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record.
Claim Rejections - 35 USC § 112
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 22-25 and 32-45, 48-49 are rejected under 35 U.S.C. 112(a) 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.
Applicant claims a administering “a TGFβ inhibitor” and “immune checkpoint inhibitor”. While the instant specification discloses several antibodies capable of inhibiting TGFβ (see, e.g., Examples), this is not considered to be representative of the vast and unknowably large structural diversity encompassed in the instant claims. Similarly, the instant claims encompass administration of any and all types of immune checkpoint inhibitors, when only anti-PDL1 antibodies are described (see, e.g., Examples).
Generic claims drawn to substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. See Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
Along these same lines, a more recent Federal Circuit decision, Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), describes how when an antibody is claimed 35 U.S.C. § 112(a) requires adequate written description of the antibody itself not just a description of the sequence to which the antibody binds. See Amgen, 872 F.3d at 1378-79.
Therefore, claiming inhibitors solely with reference to said functional property, e.g., claiming the genus of all inhibitors, which encompass small molecules, nucleotides, antibodies, etc., that inhibit TGFβ would not be sufficient to meet the written description requirement when the structures of antibodies having those properties have not been adequately described. See MPEP § 2163.
Claims 22-25 and 30-49 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the measurement of CD8-positive cells and combined treatment with TGF-β and immune checkpoint inhibition in bladder cell cancer and melanoma, does not reasonably provide enablement for doing so in all cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims.
The claims require a method of treating cancer in a subject comprising measuring CD8-positive cells in a tumor, margin, and stroma compartments from a tumor sample obtained from the subject followed by administering a combination therapy comprising a TGF-β inhibitor and immune checkpoint inhibitor, if the level of CD8-positive cells is at least 5% higher in the stroma and/or margin compartments relative to the tumor compartments, wherein cancer encompasses both any cancer type.
State of the prior art/Predictability of the art.
The prior art demonstrates that an additive anti-tumor response with combining a TGF-β inhibitor with an immune checkpoint inhibitor depends on the type of cancer1, 2
Working examples.
Working examples only investigate bladder cell cancer and melanoma (see, e.g., Example 30 in particular).
Guidance in the specification.
The specification does not provide guidance on, e.g., cancers with minimal T-cell infiltration or TGF-β-driven tumor immune evasion.
Amount of experimentation necessary.
Undue additional research is required in order to determine if embodiments of the instant invention are operable. Additional research would be undue because there is no reasonable expectation that the proposed invention will be operable in treating all cancers e.g., cancers with minimal T-cell infiltration or TGF-β-driven tumor immune evasion. Thus, there is insufficient information provided in order for an artisan to design and execute an experiment to test cancers other than bladder cell cancer and melanoma, if any, will respond to the instant invention as claimed.
For the reasons discussed above, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with this claim and it would require undue experimentation for one skilled in the art to use the claimed methods.
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 42-43 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.
Claims 42-43 are indefinite in the recitation of “wherein the TGFβ inhibitor is used in conjunction with at least one additional therapy selected from…”, as it is unclear whether the additional therapy is in addition to the “immune checkpoint inhibitor” recited in instant claim 22. Appropriate correction and/or clarification is required.
Priority
The earliest effective U.S. filing date afforded the instantly claimed invention has been
determined to be 11 January 2020, the filing date of Provisional Application No. 62/959,909, to which Int. Application No. PCT/US2021/012969 claims priority to.
Conclusion
Claims 22-25 and 32-49 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Friday 5:00AM - 2:30PM PT.
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/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 Sow, H. S., Ren, J., Camps, M., Ossendorp, F., & ten Dijke, P. (2019). Combined Inhibition of TGF-β Signaling and the PD-L1 Immune Checkpoint Is Differentially Effective in Tumor Models. Cells, 8(4), 320.
2 Löffek, S. (2018). Transforming of the tumor microenvironment: Implications for TGF‐β inhibition in the context of immune‐checkpoint therapy. Journal of oncology, 2018(1), 9732939.