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 11/07/2024 is acknowledged.
Claims 1-2, 5, 7-23 and 26-37 are pending.
3. The title of the invention is not descriptive, because “D3” is typically understood by those skilled in the art as referring to vitamin D3. A new title is required that is clearly indicative of the invention to which the claims are directed.
4. 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.
5. Claims 1-2, 5, 7-23 and 26-37 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) Claims 1-2, 5, 7-15, 18-21 and 26-37 are indefinite in the recitation of “D3,” because the identity of the product is unknown. Applicant is invited to consider using “DLL3,” the standard name of the protein.
(ii) Claims 9 and 14 are indefinite in the use of exemplary language “such as,” because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
(iii) Claim 10 is indefinite in the recitation of “cyno” D3, because the meaning of the term is unknown.
(iv) Claim 10 is further indefinite in the recitation of “EC50s at nM grade,” because (a) it is unclear whether the term “nM grade” is different in scope from the term “nanomolar range” typically used by those skilled in the art, and (b) the EC50 value that defines whether or not a given molecule is within the scope of the claim is unknown.
(v) Claim 20 is indefinite in the recitation of the term “modulating,” because it is ambiguous as to the direction (positive or negative) of the effect on the immune response.
(vi) Claim 20 is further indefinite in the recitation of “D3 related immune response,” because the nature or degree of “relatedness” (e.g. direct or indirect) are not defined.
(vii) Claim 20 is further indefinite in the recitation of “a subject,” because the subject population is not defined.
(viii) Claim 21 is indefinite because of the following contradiction: one of the embodiments of the claim is directed to a method of “preventing” cancer, “wherein the cancer is D3 positive or overexpresses D3.” “Preventing” cancer means performing the method steps before cancer exists, and a cancer which does not exist cannot be D3 positive or overexpress D3.
(ix) Claim 26 is indefinite in the recitation of a kit for “diagnosing” generically recited cancer, because it is unknown how the D3-binding molecule contained in the kit can be used to determine whether or not a generically recited cancer is present.
(x) Claim 37 is indefinite in the recitation of “D3-binding molecule to bound,” because the meaning of the phrase is unknown. It appears to contain a typographical error, but the intended meaning of the phrase is unclear.
(xi) Claim 37 is further indefinite in the recitation of the phrase “presence or absence ... of the D3-binding molecule” in the sample, because the D3-binding molecule is not expected to be naturally present in a sample obtained from a subject.
(xii) Claim 37 is further indefinite, because it is unknown how the “presence or absence,” or the “level of association,” is related to the outcome of “diagnosing.”
(xiii) Claim 37 is further indefinite in the recitation of “target molecules,” because their identity is unknown.
(xiv) Claims 2, 5, 7-23 and 26-37 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.
6. 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.
7. Claims 21-23 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a method for treating a D3-positive or D3-overexpressing cancer comprising administering the recited D3-binding molecule, does not reasonably provide enablement for a method for preventing a D3-positive or D3-overexpressing cancer comprising administering the same molecule.
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.
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 only effective approaches to cancer prevention 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).
The specification provides no 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 cancer, 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 cancer. Accordingly, the entire scope of experimentation required to develop methods of preventing cancer by administering the recited D3-binding molecule 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.
8. Claims 27, 29, 31 and 33 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a D3-binding molecule comprising CDR1, CDR2 and CDR3 sequences from the same antibody, does not reasonably provide enablement for a D3-binding molecule comprising CDR sequences from different antibodies.
The specification does not enable one of skill in the art to make and use the invention commensurate with the scope of the 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.
The specification discloses in Example 2 and Tables A and B that the VHH amino acid sequences of D3-binding molecules recited in claim 1 originate from at least four distinct antibodies independently produced by immunization of Camelidae animals and phage display.
It is well established in the antibody arts that the formation of a functional antigen-binding site generally requires all six CDRs (three CDRs in the case of VHH) to contribute contact residues for binding to the target epitope. For example, D’Angelo et al. (2018) found that while different HCDR3s can be identified within a target-specific antibody population after in vitro selection, the majority of antibodies with the same HCDR3 sequence within unselected populations do not bind the target (e.g. the Abstract).
Therefore, it is unpredictable whether the molecules as defined by the claims, which may contain CDRs from different antibodies, have the D3-binding function. The specification provides insufficient direction or guidance regarding how to produce functional antibodies broadly defined by the claims. Undue experimentation would be required to make and use the invention commensurate with the scope of the claims based on the disclosure as-filed.
9. Conclusion: no claim is allowed.
10. 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.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
Prosecution Insights