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 without traverse of Group I and species of antibody that binds CD73 which comprises the CDRs of species (5) in the reply filed on 08/27/2025 is acknowledged.
The restriction requirement is made final.
Specification
The disclosure is objected to because of the following informalities: In paragraph [0004], last sentence, “no antibodies has been” should be --no antibodies have been--. In [0022] last line, “cells causes” should be --cells cause--. In [0041], first sentence, “a tumor is shrunk is known” is confusing.
Appropriate correction is required.
The use of the term GL Sciences ([0058], [0072]), Promega ([0060], [0099]), biolegend ([0092], [0095], [0096]), Origene ([0093]), and Miltenyi ([0102]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is encouraged to carefully review the specification for other occurrences of the above trade name or mark and for those in the specification not listed above.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See [0084] and [0127].
Information Disclosure Statement
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.
Nucleotide and/or Amino Acid Sequence Disclosures
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 patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), 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 the USPTO patent electronic filing system 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 the USPTO patent electronic filing system 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:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figs. 2, 5-1, 5-2, 14-1 and 14-2.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The legend on Figure 24 recites “Blue” and “Red”, but no color appears.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Interpretation
Claim 1 in the preamble says “comprising complementarity determining regions of any combination of heavy and light chains selected from the group consisting of:…” This is being interpreted as meaning any combination of the heavy and the light chain as set forth in (1) or (2) or (3)… or (8), and not meaning mixing-and-matching of a heavy chain from one set and light chain from another (e.g., not heavy chain CDR1-3 of (1) and light chain CDR1-3 of (3)). There is no disclosure of switching heavy or light chains or CDRs thereof between different disclosed antibodies. However, it is acknowledged that in claim 1, species (5) and (7) [antibodies _006 and _008] have the same light chain CDR1-3.
Claim Objections
Claim 11 is objected to because of the following informalities: The end of claim 11 says “colorectalcancer colorectal cancer”. It appears the “colorectalcancer” was intended to be deleted. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-12, 14 and 16 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-10, 12, 14 and 16 are indefinite because they recite “human-type antibody derivative”. The specification does not define the term but only provides examples, e.g., [0017] where the antibody is described by binding CD73 and suppressing cancer and may have certain 3 heavy and 3 light chain variable region CDRs. While claim 3 lists types of human-type antibody derivatives which are human-type antibody variants selected from a humanized antibody, a chimeric antibody, a polyvalent antibody and a multispecific antibody, or a functional fragment thereof, it is unclear what about a polyvalent or multispecific antibody make it a human-type derivative. Also, it is unclear what the difference between a human-type antibody derivative and a human-type antibody variant is (see claim 3). What is encompassed by a “human-type antibody derivative” is unclear and, as a result, the metes and bounds of the claims is unclear.
Claims 10 and 11 are indefinite because a composition must comprise more than one component. It is unclear what the composition includes besides the antibody or human-type antibody derivative according to claim 1, and it is unclear if the antibody or derivative is an active ingredient of the composition or merely present in trace amounts. Knowing whether the antibody or derivative is critical to the composition is necessary to understand the breadth of the claim. If the antibody or derivative is the active ingredient, this rejection could be obviated by adding to the end of the claim a phrase such as, “and a diluent”.
Claim 12 is indefinite because it recites measuring AMP metabolism … “under a culture condition”. There is nothing in the claim about any particular parameters of the culture condition. It is unclear if the phrase means any culture condition or refers to a particular unspecified culture condition (e.g., in vitro).
Claim 12 is also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted step is: measuring cytotoxicity. The claim is indefinite because there is no connection between measuring whether or not AMP metabolism of the cancer cells from the subject which are contacted with the antibody or derivative of claim 1 has to do with measurement of cytotoxicity. Cytotoxicity is generally defined by damage or death of a cell. There is nothing in the claim measuring that.
Claim 14 is indefinite because it is unclear if in vitro AMP metabolism suppression is being designated as an indicator of enhancement of cytotoxicity against cancer cells collected from a subject administered the antibody or human-type antibody derivative. If it is, then this should be made clear.
Claim 14 is also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted step is: when the administration to the subject takes place relative to the in vitro cancer cell AMP metabolism measurement. Both the chronological connection as well as whether the cancer cells of the in vitro assay are the same ones (not merely the same type of cancer cells) which are/were subjected to enhancement of cytotoxicity after administration to the subject.
Claim 16 recites the limitation "the cancer cell collected from the subject" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(d)
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.
Claim 16 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. Claim 16 is drawn to a “measurement kit comprising the antibody or the human-type antibody derivative according to claim 1…”. It then recites an intended use. However, there is nothing to distinguish the kit from the antibody or human-type antibody derivative of claim 1 because claim 16 has nothing in addition to the antibody or the human-type antibody derivative recited in claim 1. As a result, claim 16 does not further limit claim 1. 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(a)
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.
Claim 7 is 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.
Claim 7 is drawn to an antibody or human-type antibody derivative according to claim 1 which induces cytotoxicity against cancer cells but not against normal cells. There are two issues related to lack of written description for the instant claim. First, not all cancer cells express CD73, to which the antibody binds. If the cancer cell does not express CD73, the instant antibody would not reasonably be expected to induce cytotoxicity against it. While most cancers appear to express some CD73 protein at some level, not all do (e.g., The Human Protein Atlas, NT5E, Cancer, https://www.proteinatlas.org/ENSG00000135318-NT5E/cancer 2025, “Protein Expression Summary” graph states “Lymphomas and testicular cancers showed weak positivity or were negative”,)
Second, normal cells are known to express CD73 (e.g., The Human Protein Atlas, NT5E, https://www.proteinatlas.org/ENSG00000135318-NT5E, 2025, “Protein Expression and Localization”). The specification has not described how to not induce cytotoxicity against normal cells which express CD73. Chen et al. (Immunotherapy (2019) 11(11), 983–997, p. 983, middle) teaches that CD73 is a receptor found not only on tumor cells but also on stromal cells such as endothelial cells and certain leukocytes. Further, in pathological conditions including inflammation, ischemia and hypoxia, CD73 protects tissue from destruction (p. 983, middle). It also promotes immunosuppression by generating adenosine, which induces regulatory T cells (p. 983, last paragraph). However, Chen teaches that one report found decreased CD73 expression in poorly differentiated advanced-stage endometrial carcinoma and ovarian high-grade serous carcinoma and CD73-generated adenosine inhibits their disease progression (p. 984, first paragraph). Nevertheless, the adenosine that CD73 activation generates usually suppresses antitumor immunity (p. 990, fourth paragraph). CD73 expression is generally recognized as correlating with poor cancer prognosis and CD73 is expressed by many different cancers and promotes tumor growth and metastasis (p. 984, second paragraph). In vitro and in vivo research on CD73 led to the conclusion that (p. 984, last sentence), “These results indicate a complex and contextual role for CD73 in regulating cancer cell viability, stemness and immune suppression, warranting further investigation in vivo.” This is shown also by CD73 expression in prostate epithelium being associated with immune suppression and progression of prostate cancer but in stroma associated with good disease prognosis (p. 987, end of first full paragraph).
Example 11 of the specification shows antibody binding to cells endogenously expressing CD73. Example 18 showed these same cells (MDA-MB-231) used in a breast cancer mouse model when treated with the antibody led to a tendency for increase in tumor-infiltrating T cells. Example 20 shows (Fig. 31) when a human CD73 knock-in mouse model with transplanted colorectal cancer cell line expressing human CD73 was treated with an anti-mouse PD-L1 antibody combined with anti-CD73 002_6_h4 antibody, there was slightly lower, though insignificant, reduction in tumor volume compared to the combination of an isotype hIgG and the anti-PD-L1 antibody. In the examples of the specification, the cancer or cancer cells to be treated expressed CD73.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). It does not appear applicant was in possession of an antibody or human-type antibody derivative which induces cytotoxicity against cancer cells that do not express CD73 and, separately, which induces cytotoxicity against cancer cells expressing CD73 but not normal cells.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
US Patent 11,613,577 B2 teaches anti-CD73 antibodies and showed that one, Hu101-28, increased T cell response measured by IFNgamma production (e.g., Figs. 16-17). It did so by blocking enzymatic activity of CD73 and inducing internalization of the cell surface CD73 (Example 8). The antibody was able to inhibit tumor growth in a mouse A375 xenograft model (Example 10). The antibody had a different sequence than the elected species of the instant application. This shows the state of the art for anti-CD73 antibodies.
US 11,312,785 B2 teaches anti-CD73 antibodies (Table 9) which reduce cell surface levels of CD73 (Example 4), inhibit adenosine production (Example. 5) and induce T cell proliferation and IFNgamma release (Example. 6). The antibodies have a different sequence than the elected species of the instant application. This also shows the state of the art for anti-CD73 antibodies.
Allowable Subject Matter
Claim 1 would be allowable for the elected species if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. Note there is no generic claim.
Claims 2-6, 8-12 and 14 would be allowable for their elected specie if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims if independent claim 1 is rewritten or amended to also overcome the rejection under 35 USC 112(b) set forth in this Office action (see above).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Official papers filed by fax should be directed to (571) 273-8300. NOTE: If applicant does submit a paper by fax, the original signed copy should be retained by the applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
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 .
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
October 16, 2025