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 03/11/2024 is acknowledged.
Claims 24, 35, 38, 49, 57, 59, 61, 83-90, 92, 95, 117-118 and 122 are pending.
3. The specification is objected to because page 66 of the specification as-filed (dated 08/22/2023) is blank. While it is not clear whether any text is missing, appropriate correction or clarification is required in response to this office action.
4. Claim 61 is objected to because of an apparent typographical error in the phrase “peripheral blood lymphocytes, or T cells r CD4+ and/or CD8+ cells” (emphasis added). Appropriate correction or clarification is required.
5. 35 U.S.C. § 101 reads as follows:
"Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title".
6. Claim 86 rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claim is directed to "a cell" comprising the recited antibody, nucleic acid, vector, or conjugate, but does not specifically limit the cells to non-human cells or to cells in vitro. Therefore, the term "cell" in is interpreted to encompass, inter alia, a cell present in a human being, and therefore being inseparable from the human being itself. The scope of the claim, therefore, encompasses a human being, which is non-statutory subject matter. See 1077 O.G. 24, April 21, 1987. Applicant is invited to consider amending the claim to recite "isolated" and/or "non-human" cell to overcome this rejection.
7. 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.
8. Claims 24, 35, 38, 49, 57, 59, 61, 83-90, 92, 95, 117-118 and 122 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) Claim 24 is indefinite in the recitation of an antibody or antigen binding fragment which is capable of specifically binding to a generically recited sialic acid-binding immunoglobulin-like lectin (Siglec), because it is unknown which of the 14 diverse members of the Siglec family (e.g. Van Houtum et al., 2021) the antibody binds to.
(ii) Claim 24 is further indefinite in the recitation of a “Siglec or a functionally active fragment thereof,” because it is unknown which Siglec function(s) is/are within the scope of the claim.
(iii) Claim 59 is indefinite in the recitation of an antigen-binding fragment selected from “one or more of the groups consisting of” Fab, Fab', a Fv fragment, F(ab')2, F(ab)2, scFv, di-scFv, VHH, and dAb, because it is unknown what groups the listed formats are grouped into.
(iv) Claims 61, 90, 95, 118 and 122 are indefinite in the recitation of the term “include,” because the scope of the limitations following the term is unclear. While the claim and ordinary meaning of the verb “to include” is similar to “to comprise,” in the context of the claims the word “includes” appears to be used to mean “is,” e.g. “Siglec includes [is?] Siglec-15,” “immune cells include [are?] immune cells derived from human,” “cytokine includes [is?] an inflammatory factor,” condition included [is?] colon cancer,” etc.
(v) Claims 61 and 118 are indefinite in the use of the term “preferably,” because it is unclear whether or not the preferred embodiments constitute claim limitations. Description of examples or preferences is properly set forth in the specification rather than the claims.
(vi) Claim 61 is indefinite in the recitation of the ability to inhibit a tumor with “a tumor” volume inhibition rate of about 23% or more, because it is unknown what tumor and under what conditions are inhibited by the recited quantitative value. Tumor inhibition critically depends on the specific tumor type and the specific conditions, as a person of skill in the art would be aware.
(vii) Claim 61 is further indefinite in the recitation of the ability to inhibit a tumor with a tumor volume inhibition “rate” of about 23% or more, because “rate” is change of a value over a unit of time, and time is not specified in the claim.
(viii) Claim 61 is further indefinite in the recitation of “an inflammatory factor,” because it is unclear what types inflammatory factors (e.g. dietary choices, lifestyle habits, environmental exposures) are within the scope of the claim.
(ix) Claim 61 is further indefinite in the recitation of the following phrase (emphasis added): “the immune cells include lymphocytes, or peripheral blood lymphocytes, or T cells r [sic] CD4+ and/or CD8+ cells,” because the mixing of conjunctions “or” and “and/or” makes it unclear whether the limitations are required to be present in the alternative or together.
(x) Claims 86 and 92 are indefinite in the recitation of a cell comprising the “immunoconjugate” comprising the antibody or antigen binding fragment according to claim 24. According the specification, ‘the term “immunoconjugate” generally refers to a conjugate formed by the conjugation of other reagents (e.g., a chemotherapeutic agent, a radioactive element, a cytostatic agent, and a cytotoxic agent) to the antibody or antigen-binding fragment thereof (e.g., via covalent attachment of a linking molecule)’ ([0199] of US 20240124576). Accordingly, an immunoconjugate is formed in vitro, by chemically binding a reagent to an antibody. Therefore, a cell cannot “express” an immunoconjugate, and so it is unclear what is meant by a cell comprising the immunoconjugate.
(xi) Claim 95 is indefinite, because it is unclear how detecting Siglec in a sample is accomplished by administering the antibody (or nucleic acid, vector, etc.), or whom the antibody (or nucleic acid, vector, etc.) is administered to.
(xii) Claim 95 is further indefinite in the recitation of “using” the kit, because the claim does not set forth any active, positive steps delimiting how “using” is actually practiced.
(xiii) Claim 117 is indefinite in the recitation of “a disease and/or condition,” because the target subject population is not defined.
(xiv) Claim 117 is further indefinite in the recitation of “administering the kit comprising the antibody or antigen binding fragment according to claim 24.” A person of skill in the art would be aware that a kit comprising a therapeutic antibody typically comprises the antibody packaged in a container, such as a vial or a syringe, and instructions for use. It is unclear how administering a vial or instructions may contribute to prevention or treatment of a disease or condition.
(xv) Claim 117 is further indefinite, because the recitations of “the nucleic acid molecule,” “the vector,” “the immunoconjugate,” “the cell,” “the pharmaceutical composition,” “the pharmaceutical combination,” and “the kit” lack proper antecedent basis in the base claim.
(xvi) Claim 118 is indefinite in the recitation of Siglec15-“associated” tumor, because neither the nature nor the requisite degree of the association is defined.
(xvii) Claims 35, 38, 49, 57, 59, 61, 83-90, 92, 95, 117-118 and 122 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.
9. 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.
10. Claims 117-118 and 122 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a method of treatment of a Siglec-15-positive tumor,
does not reasonably provide enablement for:
(i) a method of prevention of any disease and/or condition, including a Siglec-15-positive tumor, or
(ii) a method of treatment of a generically recited “disease and/or condition,” including generically recited tumor, generically recited solid tumor, Siglec15-“associated” tumor, or colon cancer.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims without undue experimentation.
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.
(i) In the medical context, preventing a disease involves identifying healthy human subjects susceptible the disease, applying the treatment, and, after a sufficiently long period of time has elapsed, ascertaining that the absence of the disease in the subjects is due to the treatment and not some other factors. Therefore, the burden of enabling a method of preventing a disease is much greater than that of enabling a method of treating a disease, due to the inherent difficulty of identifying healthy human subjects susceptible the disease, and especially the hurdle of proving that the administered treatment was the factor that resulted in prevention of the disease. The specification does not appear to provide sufficiently specific working examples, guidance or direction as to how one skilled in the art would screen the population to select the subjects in need of prevention of any of the diseases within the scope of the claims, nor is guidance or direction provided as to the protocol to be utilized in order to establish the efficacy of the claimed treatment in preventing these conditions.
Regarding cancer prevention, the only effective approaches known in the art are those based on lifestyle changes (see e.g. Balducci, 2016). “Although a number of agents are available for the chemoprevention of breast and prostate cancer, so far none of them has yielded a reduction of cancer-related death.” (Id., p. 321). Accordingly, the entire scope of experimentation required to develop methods of preventing cancer of any disease or condition by administering the recited antibody 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. Given the resource-intensive nature of the required experimentation, the risks involved and the extremely low expectation of success, the skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
(ii) Regarding treating a generically recited “disease and/or condition,” a person of ordinary skill in the art would have been aware of the enormous variety of pathological processes in terms of etiology, pathogenesis, and molecular and cellular mechanisms, and so a great majority of diseases would not be treatable by any single therapeutic intervention. In the absence of sufficient guidance, direction, or working examples in the present disclosure, it is at best unpredictable whether a given disease out of a practically infinite number of diseases encompassed by the scope of the claims is treatable by the recited antibody; thus the experimentation left to those skilled in the art would be unnecessarily, and improperly, extensive and undue.
Regarding treating a generically recited tumor, solid tumor, or colon cancer, the precent specification discloses in Example 6 that Siglec-15 protein suppresses T cell proliferation, and anti-Siglec-15 antibodies reverse the suppression (Figs. 5 and 6), i.e. the effect of anti-Siglec-15 antibodies is based upon their binding to Siglec-15. This is consistent with the teachings of Wang et al. (2019, cited on IDS), who found that Siglec-15 suppresses antigen-specific T cell responses in vitro and in vivo, and antibody blockade of Siglec-15 amplifies anti-tumor immunity in the TME and inhibits tumor growth in some mouse models (e.g. the Abstract). Wang concludes that Siglec-15 is a potential target for cancer immunotherapy, and announces a phase I clinical trial to test the effect of a humanized mAb (NC318) to Siglec-15 in solid tumors (NCT03665285) (p. 664).
Accordingly, anti-Siglec-15 antibodies affect anti-tumor immune response, and thereby tumor growth, only in Siglec-15-positive tumors, whether Siglec-15 is expressed by the tumor cells or by other cells in tumor microenvironment. Therefore, any experimentation aimed at treating Siglec-15-negative tumors would almost certainly be unsuccessful, and as such unnecessary, improper and undue. Regarding Siglec15-“associated” tumors, it is not clear whether such tumor is Siglec-15-positive (see subsection 8(xvi) above), and therefore the same considerations as presented above in this paragraph apply Siglec15-“associated” tumors.
11. The following prior art and post-filing date documents are cited of record as pertinent to the present invention:
US 9464133 teaches and claims administering anti-Siglec-15 antibody to subjects suffering from bone destruction accompanying multiple myeloma or cancer metastasis to bone, or giant cell tumor (e.g. claims 1, 7, 8, 10, 14 and 16).
Stanczak et al. (2023) Siglec receptors as new immune checkpoints in cancer. Molecular Aspects of Medicine 90:101112, p. 1-9.
12. Conclusion: no claim is allowed.
13. 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