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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 03/26/2026 is acknowledged. The traversal is on the ground(s) that there is no undue burden placed on the Examiner to search and consider all claims. This is not found persuasive because the instant application is a 371 of PCT/US2022/021274 and thus the election requirement was made under the unity of invention guidelines, which do not consider search burden when restricting claims. Therefore, Applicant's argument is moot.
The requirement is still deemed proper and is therefore made FINAL.
Claims 13-23 and 30-36 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/26/2026.
Status of Claims
Claims 1-23 and 29-36 are pending. Claims 13-23 and 30-36 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 03/26/2026. Claims 1-12 and 29 will be examined on the merits.
Priority
Provisional application 63/164,137 is acknowledged as disclosing the claimed invention and the effective filing date is 03/22/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 09/14/2023 has been considered. Signed copies are enclosed.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 7 is objected to because of the following informalities: claim 7 recites an effective amount of an antibody "as defined in" claim 1. Claim 1 recites limitations of the CDRs of the antibody, but does not define a single specific antibody. Suggested language would include “the antibody…of claim 1” or “an antibody…as recited in claim 1”. Appropriate correction is required.
Claim 29 is objected to as it is dependent on a non-elected claim. Claim 29 recites the method of claim 13 in the preamble. Although this is an intended use limitation of the claim and therefore does not bear patentable weight, the preamble should still be amended so as to not refer to a non-elected claim.
Claim Interpretation
Claim 8 recites “the method of claim 7, wherein the disease or disorder is a cancer and a metastasis thereof.” Examiner is interpreting this to mean the disease or disorder is only a cancer that has metastasized, as the claim as written requires both a cancer and a metastasis thereof. If this interpretation is incorrect, Examiner suggests amending the claim for clearer language.
Claim Rejections - 35 USC § 112
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.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “prolong survival time” in claim 12 is a relative term which renders the claim indefinite. The term “prolong survival time” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As written, the amount of time the subject must survive after treatment in order to be considered "prolonged survival time" is unclear, as neither the claim nor the specification recite a definition and the term is subjective in the art.
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 7 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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.
The instant claims are drawn to a method for inhibiting enolase 1 (ENO1)-downstream signaling and/or treating a disease or disorder associated with activation of ENO1-downstream signaling comprising administering to a subject an effective amount of the antibody as defined by claim 1. Further claims limit the disease or disorder to a metastasized cancer (as set forth under claim interpretation above), selected from the group consisting of lung cancer, brain cancer, breast cancer, cervical cancer, colon cancer, gastric cancer, head and neck cancer, kidney cancer, leukemia, liver cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer and testicular cancer, and most specifically, metastasized lung cancer. Other claims are drawn to administering an effective amount of the antibody, either to inhibit tumor growth and metastasis in the subject, or to prolong survival time in the subject.
The specification teaches, in paragraph [0088], that activation of ENO-1 downstream signaling is associated with a proliferation disease or disorder, for example, a cancer and a metastasis thereof. The specification does not give any other examples of a disease or disorder associated with activation of ENO1-downstream signaling beyond the list of cancers that includes “lung cancer, brain cancer, breast cancer, cervical cancer, colon cancer, gastric cancer, head and neck cancer, kidney cancer, leukemia, liver cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer and testicular cancer, which have been observed to have the features of overexpression of ENOl mRNA or protein.” Paragraph [0089] of the specification teaches that “an effective amount” is the amount of active ingredient (i.e. antibody) to confer a desired effect, and will vary based on many factors, and can be determined by one skilled in the art of dosing. Paragraph [0090] teaches that the subject can be a mammal, more preferably a human, and that a subject in need of treatment may have a target disease/disorder associated with activation of ENO1-downstream signaling, and again only provide the example of cancer. Paragraph [0091] only teaches a subject in need to be treated by the method possesses cells or tissues that overexpress ENO1. The examples in the specification teach that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors, and is associated with poor survival in cancer patients (paragraph [00113]). The examples provide support for the claimed invention via in vitro cell line experiments and in vivo lung cancer murine model experiments (paragraphs [00165-00168], figures 7-8).
Therefore, sufficient support is presented in the specification for a method of inhibiting ENO1-downstream signaling using the disclosed antibody, as evidenced by the data in figures 7E-I. Moreover, sufficient support is presented in the specification for claim 10, which specifies that the disease associated with activation of ENO1-downstream signaling is lung cancer.
The specification does not provide any other examples of ENO1-associated diseases outside of cancers, and does not provide any working examples beyond lung cancer.
The art supports the role of ENO1 as an oncoprotein in a variety of cancers, as taught by Huang et al., (2022) Mol Ther Oncolytics Jan 3;24:288-298. Therefore, the specification and the state of the art support a method of treating a metastasized cancer wherein the cancer is selected from the group consisting of lung cancer, brain cancer, breast cancer, cervical cancer, colon cancer, gastric cancer, head and neck cancer, kidney cancer, leukemia, liver cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer and testicular cancer. Moreover, the specification defines ‘an effective amount’ as the amount of antibody needed to reduce tumor growth, which is supported for lung cancer in the examples (figure 8A-B) and can be extrapolated to other forms of cancer in view of Huang et al.
However, there is no support in the specification for any disease or disorder associated with ENO1 signaling. Several autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and vasculitis, are hallmarked by overexpression of ENO1, or auto-anti-ENO1 antibodies circulating, as are many cancers (Angeletti et al, (2021), Autoimmunity reviews, 20(12), 102977). However, manifestations of autoimmune diseases and cancer are very different, as evidenced by Elkoshi ((2022) Front. Immunol. 13:821598). There is no evidence provided in the art or in the specification that treatment with an anti-ENO1 antibody will successfully treat an autoimmune disease marked by aberrant ENO1 signaling. Moreover, the specification only identifies proliferation diseases or disorders, and autoimmune diseases do not all feature proliferation issues, as cancers do. Therefore, claim 7 as written does not have sufficient written description support that the Applicant had, at the time of filing, a method of treating any disease or disorder associated with activation of ENO1-downstream signaling.
Finally, claim 12 is drawn to administering an effective amount that will “prolong survival time” in the subject. As recited in paragraph 13 above, the term “prolong survival time” is indefinite, as no parameters for prolonged survival are recited in the claim or specification. Figure 8C in the specification shows that antibody administration does extend survival, but with a great amount of variation in the amount of time survived, and the median survival is only increased by a few weeks (11 to 17 days, depending on the dose). More clarity is needed to determine if claim 12 is adequately supported by the specification.
Taken together, claims 7 and 12 do not meet the written description requirement of USC 112(a).
Allowable Subject Matter
Claims 1-6 are allowed.
The following is an examiner’s statement of reasons for allowance: The antibody of claim 1, the further limited antibody of claims 2 and 3, and the nucleic acid, host cell, and composition that feature the antibody of claim 1 are free of the art as of the effective filing date, 03/22/2021.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Claims 8-11 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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