Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election/Restrictions
2. Applicant’s election without traverse of antibody 1A, having a variable heavy chain of SEQ ID NO: 235 (CDRs of SEQ ID NOs: 266, 267 and 268) and a variable light chain of SEQ ID NO: 236 (CDRs: SEQ ID NOs: 269, 270 and 271), as the species of antibody that binds to calcium channel flower homolog protein, and cancer as they species of disease/disorder, in the reply filed on 22 June 2026 is acknowledged. Election was made without traverse in the reply filed on 22 June 2026.
Status of Application, Amendments, and/or Claims
3. The Response filed on 22 June 2026 has been entered in full. Claims 1-12 are pending and the subject of this Office Action.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 30 December 2025 has been considered by the Examiner.
Specification
Nucleotide and/or Amino Acid Sequence Disclosures
5. REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via EFS-Web or Patent Center as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web or Patent Center as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
The file size is incorrect (See image below for correct file name and size).
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Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version), with the file size in bytes;
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Improper Markush
6. Claims 1-2, 5-6 and 8-9 are rejected (and dependent claims 3-4, 7 and 11-12 are also rejected) on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
7. In the instant case, the Markush grouping of antibodies which bind a calcium channel flower homolog protein recited in claims 1-2, 5-6 and 8-9 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the various antibodies do not share a substantial structural feature as they all have different amino acid sequences, and they bind to different antigens or epitopes thereof. Therefore, there is no substantial common structural feature and a common use that flows from the substantial structural feature.
8. To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
9. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
10. Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. From the specification it is presumed that the recited function, i.e., “binds to a calcium channel flower homolog protein that behaves as Flower-Win protein”, “binds to a calcium channel flower homolog protein that behaves as Flower-Lose protein” and “binds to a calcium channel flower homolog protein that behaves as Flower-Win protein and binds to a calcium channel flower homolog protein that behaves as Flower-Lose protein”, can be attributed to the antibody as recited in claim 8. Therefore, claim 8 fails to further limit the claim from which it depends (claim 8) by altering the structure or adding additional components. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
11. 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.
12. Claims 5-7 are 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 pre-AIA the applicant regards as the invention.
13. Claim 5 is rejected as being indefinite for reciting the limitation “cellular fitness”. Since neither the art nor the Specification provide an unambiguous definition of what would constitute “cellular fitness”, the metes and bounds of the claim cannot be determined. The discussion of such at pp. 1-2 paragraphs [0004] - [0005] is noted but vague, and fails to breathe life and meaning into the term, and thus insufficient to render the claim definite.
14. Claims 6-7 are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 112 (Scope of Enablement)
15. 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.
16. Claims 5-12 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 methods of (1) treating solid tumors in a subject in need thereof, or (2) inhibiting apoptosis of stromal cells in the tumor microenvironment, does not reasonably provide enablement for methods of (1) treating any kind of cancer, or (2) treating the breadth of diseases encompassed by the instant claims. 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/or use the invention commensurate in scope with these claims.
17. Factors to be considered in determining whether a disclosure enables one skilled in the art to make and use the claimed invention in its full scope without resorting to undue experimentation include: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature or complexity of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. See In re Wands, 8 USPQ2d. 1400 (Fed. Cir. 1988).
18. In the instant case, the claims are broadly drawn to methods of increasing cellular fitness of a population of cells, or preventing apoptosis of a population of cells, or a combination thereof, comprising contacting said population of cells with an antibody that binds to calcium channel flower homolog protein. The claims also recite a method of treating a cancer, or a disease or condition in a subject in need thereof, comprising administering to said subject an antibody that binds to calcium channel flower homolog protein. Thus the claims encompass complex and unpredictable subject matter, involving the effects of complex biological molecules on diseased physiological states. As was found in Ex parte Hitzeman, 9 USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. This invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology”, Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert, denied, 502 U.S. 856 (1991).
19. The specification provides detailed direction and guidance regarding the tumor growth inhibiting effects of the claimed anti-CACFD1 antibodies. Specifically, the Specification teaches that the claimed anti-CACFD1 antibodies block competitive apoptotic elimination of stromal cells in the tumor microenvironment, and attenuate the growth/volume and metastasis of solid tumors (See pp. 114-115, for example). However, the data presented in the Specification does not provide any guidance on the treatment of the breadth of diseases or conditions encompassed or specifically recited in the claims, nor does it provide any guidance for the treatment of cancers that are not characterized by tumors, such as leukemias, lymphomas, and myelomas. Furthermore, the Specification does not provide any guidance on inhibiting/preventing apoptosis of cells that are not within the tumor microenvironment, and there are no working examples directed to such.
20. The state of the art indicates that “cancer” is an extremely broad term that encompasses many conditions that do not involve tumor formation. For example, Arber et al. (2016, Blood 127:2391-2405) provide a non-exhaustive list of over 50 types of leukemias at p. 2392, Table 1. Swerdlow et al. (2016, Blood 127:2375-2390) provide an even longer but non-exhaustive list of lymphomas at p. 2376, Table 1. None of these cancers are characterized by tumor formation. These references evidence that there are many specific types of “cancer” that are not characterized by tumors, and thus serve to illustrate the breadth of the claims compared to the more limited scope of detailed guidance and working examples provided by the application.
21. While the level of skill in the art is high, the amount of guidance provided regarding how to use the antibodies to effectively treat any of the large number of diseases/conditions, treat cancers that are not characterized by tumors, or prevent apoptosis if cells not located in the tumor microenvironment, is completely lacking. Accordingly, the amount of experimentation required to determine how to use the recited antibodies in the recited methods is quite extensive.
22. Due to the large quantity of experimentation necessary to determine how to use the recited antibodies to treat the breadth of conditions/diseases encompassed by the claims, treat cancers that are not characterized by the presence or formation of tumors, or prevent apoptosis in any population of cells; the lack of direction/guidance presented in the specification regarding the same, the absence of working examples directed to the same, the complex nature of the invention, the contradictory state of the prior art, the unpredictability of the effects of complex biological molecules on diseased physiological systems, and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Summary
23. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jon M. Lockard whose telephone number is (571) 272-2717. The examiner can normally be reached on Monday through Friday, 8:00 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached on (571) 272-2911. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JON M LOCKARD/
Examiner, Art Unit 1647
July 11, 2026
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