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 amendment, filed on 11/10/2023, is acknowledged.
3. Claims 1-14 are pending.
4. Applicant’s IDS, filed 11/10/2023, 02/17/2025, 07/15/2025, is acknowledged.
5. Claim 1 is objected to because SEQ ID NO: 1 and SEQ ID NO: 5 contain undefined amino acid (Xaa) without specifying the alternative of Xaa discloses in the Sequence Listing, for example SEQ ID NO: 1, wherein X5 is E, N or D. It is suggested to amend claim 1 to specific the Xaa positions in SEQ ID NOs: 1 and 5.
6. The following is a quotation of 35 U.S.C. 112(b) (Pre AIA , 35 U.S.C. 112, second paragraph):
(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.
7. Claim 5 is rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
The recitation “positions 92-132 in the amino acid sequence of GITR protein” in claim 5 is indefinite because it is indefinite to recite amino acid positions without structural feature as a reference, i.e., SEQ ID NO. It is not clear whether the amino acids positions refer to the mature extracellular domain starts at Q26 or at the N terminal signal peptide.
8. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
9. Claims 8-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating cancer comprising administering the anti-GITR antibody comprising the CDRs of SEQ DI NOs: 1-6, does not reasonably provide enablement for methods recited in claims 8-13. 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.
The claims are directed to a genus of methods for prevention or treatment of cancers including solid cancers and hematological cancer in claims 8-9.
Claims 10-11 encompass a broad genus of methods for immunopotentiation resulting in activating immune cells, inhibiting regulatory T cells, and increasing immune proteins.
Claims 12-13 encompass a broad genus of methods for prevention and treatment of immune-related diseases including infectious diseases, inflammatory diseases and autoimmune diseases.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized 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, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification under example 7 discloses the anti-cancer efficacy of anti-GITR antibody in MC38 Colon carcinoma model (in vivo). In particular, the specification discloses MC38 tumor cells were subcutaneously inoculated into the right flank region of C57BL6 hGITR knock-in mice. Inoculated mice were treated with anti-GITR 51 B VH3/Vk4 antibody produced in CHO cells (Group 2). The tumor size (volume) measurements are depicted in Fig. 14. The anti-GITR 51B VH3/Vk4 antibody exhibited a significant tumor growth inhibitory effect compared to control group treated with PBS.
The results of example 3 shows (Figs. 12 and13) show that the anti-GITR 51B VH3/Vk4 antibody increased cytokine (IL-2 and IFN-γ) production in CD4+ and CD8+ T cells from NSCLC HCC patient’s PBMC at a higher level than the refence antibody 28F3 in vitro (see sections 6.2 and 6.3).
Example 5 shows anti-tumor (ovarian) effect on anti-GITR antibody.
4.3. Immunomodulation of T regulatory cells (Treg) and NK cells by anti-GITR antibody.
4.2. Enhancement of CD8+ T cell proliferation by anti-GITR antibody.
The scope of the claims encompasses the treatment and prevention of each and every cancer, each and every immune-related disease including each and every infectious disease, each and every inflammatory disease and each and every autoimmune disease and immunopotentiation/enhancement of immune response with the claimed anti-GITR 51 B VH3/Vk4 antibody.
The specification does not provide exemplification of animal model to treat and prevent each and every cancer, each and every immune-related disease including each and every infectious disease, each and every inflammatory disease and each and every autoimmune disease and immunopotentiation/enhancement of immune response with the claimed anti-GITR 51 B VH3/Vk4 antibody. Besides cancer, no effect of any therapy was administered to treat or prevent each and every each and every immune-related disease including each and every infectious disease, each and every inflammatory disease and each and every autoimmune disease and immunopotentiation/enhancement of immune response with the claimed anti-GITR 51 B VH3/Vk4 antibody.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized 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, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
Besides the cancer killing, the specification fails to provide enablement for preventing cancers, treating and preventing each and every immune-related disease including each and every infectious disease, each and every inflammatory disease and each and every autoimmune disease and immunopotentiation/enhancement of immune response with the claimed anti-GITR 51B VH3/Vk4 antibody.
Given the relatively incomplete understanding in correlating between the 51B VH3/Vk4 antibody and in vivo animal models to clinical treatment and prevention each and every cancer, autoimmune disease, each and every inflammatory disease, each and every inflammatory disease, and immunopotentiation/enhancement of immune response involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims, the claims are not enabled. See MPEP 2164.08.
In re Fisher, 166 USPQ 18 indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are drawn to the treatment of patients suffering from each and every cancer, autoimmune disease, each and every inflammatory disease, each and every inflammatory disease, and immunopotentiation/ enhancement of immune response using the anti-GITR antibody 51B. No working empirical data demonstrated that the anti-GITR antibody 51B would be use for the claimed treatments. The specification lacks empirical data on the in vivo efficacy of the anti-GITR antibody 51B on subjects suffering from each and every cancer, autoimmune disease, each and every inflammatory disease, each and every inflammatory disease, and immunopotentiation/ enhancement of immune response. The experiments in the specification never successfully used the anti-GITR antibody 51B to treat and prevent each and every cancer, autoimmune disease, each and every inflammatory disease, each and every inflammatory disease, and immunopotentiation/enhancement of immune response.
The lack of any working examples is exacerbated because the invention is in a highly unpredictable art-autoimmune/inflammatory/cancer/immunopotentiation related disorders - and while the level of skill of in the art may be high, the state of the prior art is that it is in fact unknown and untested what are the underlying molecule and physiologic bases of the therapeutic effects of the anti-GITR antibody, 51B in the related disorders with anti-GITR antibody 51B.
Importantly, Davar (Targeting GITR in cancer immunotherapy – there is no perfect knowledge, Oncotarget, 22 Jun 2023) reported that multiple GITR agonist antibodies advanced to clinical trials have failed to produce significant anti-tumor activity in human patients. Overall, the clinical results obtained so far with GITR agonist agents have demonstrated specific immune effects in the expected immune cell populations based on preclinical studies. However, these effects have not produced substantial therapeutic activity in human cancer patients.
The burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to autoimmune/ inflammatory/ cancer/immunopotentiation related disorders within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized to prove the efficacy of the presently claimed anti-GITR antibody in preventing autoimmune/ inflammatory/cancer/immunopotentiation related disorders state.
If the use disclosed is of such nature that the art is unaware of successful treatments with chemically analogous compounds, a more complete statement of how to use must be supplied.
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements...However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims.” MPEP § 2164.03.
"Substantiating evidence may be in the form of animal tests which constitute recognized screening procedures with clear relevance to utility in humans. See Ex parte Krepelka, 231 USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein." Ex parte Maas, 9 USPQ2d 1746.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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September 21, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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