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 .
DETAILED ACTION
Claim Status
1. In the Amendment filed on 17 February 2026, claims 20 and 23 were modified. Claims 1-19, 21, and 35-36 were canceled without prejudice or disclaimer. New claims 37-42 were added. Claims 20, 22-34, and 37-42 are under consideration.
Election/Restrictions
2. Applicant's election with traverse of Group III (claims 22-26) in the reply filed on 2/17/26 is acknowledged. The traversal is on the ground(s) that the subject matter of all the claims in Groups I, III, and IV form a single general inventive concept due to the technical relationship among the subject-matter (for example, the methods recited in Group I can be utilized in the elected method (Group III) where the number of ANTXR1+ fibroblasts are quantified). Similarly, the methods of Groups III and IV utilize the same, or similar immunotherapeutic agents for the treatment of subjects whose tumor samples comprise ANTXR1+ fibroblasts or ANTXRI+ FAP+ fibroblasts. Due to these shared technical relationships, examining Groups I, III, and IV at the same time promotes efficiency for both the USPTO and Applicants, while imposing no undue burden on the Examiner. Moreover, no unity of invention rejection was issued in PCT/EP2021/062090, of which the instant application is a U.S. National Stage Application.
This argument was carefully considered but is not found persuasive because the special technical feature of Groups I, III, and IV appears to be measuring ANTXR1+ in fibroblasts in a cancer sample as taught by Szot et al. (J. Clin. Invest. 2018, 128(7): 2927-2943) and is therefore not a special technical feature as it does not make a contribution over the prior art.
3. Applicant argues that the restriction requirement is contrary to the international standards, however, the U.S. Patent and Trademark Office is not bound by the interpretation of the prior art and claims expounded in the IPER.
4. The requirement is still deemed proper and is therefore made FINAL.
5. Claims 27-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 2/17/26. Currently claims 22-26 and 37-42 are under consideration.
Priority
6. The instant application has a priority date of May 7, 2020. This application is the U.S. national stage application of International Patent Application No. PCT/EP2021/062090, filed May 7, 2021, which claims the benefit of EP Application No. 20305454.9, filed May 7, 2020.
Information Disclosure Statement
7. 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 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the Examiner on form PTO-892 or Applicant on PTO-1449 cited the references they have not been considered.
8. The Information disclosure Statement (IDS) filed on 11/4/22 has been considered as to the merits before the First Action.
Specification
9. 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. For example, see page 43 lines 26, page 54 line 3, and page 60 line 7.
10. The disclosure is objected to because of the following informalities: The cross reference section should be updated to include “EP Application No. 20305454.9, filed May 7, 2020”. Appropriate correction is required.
Abstract
11. Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
12. The abstract utilizes legal phraseology. See “said” – Appropriate correction is required.
Claim Objections
13. Claims 22-26 and 37-42 are objected to because of the following informalities: The claims utilize several acronyms “ANTXR1, FAP, CAF, LAMP5, SDC1, CD9, CAR, and IDOI” without first defining what it represents in the independent claim. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym. For example, CAF is cancer-associated fibroblast as defined on page 1 line 25 of the disclosure. However, Applicant is cautioned not to introduce new matter into the claims. Appropriate correction is required.
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.
14. Claims 22-26 and 37-42 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.
A. The terms “low number and percentage” in claims 22 and 23 are relative terms which renders the claim indefinite. The terms are not defined by the claims, 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 recited it is not clear as to what will be considered a low number or low percentage. Therefore the metes and bounds of the claim can not be determined. It is suggested that an actual unit of measurement (a low number is less than 50 or a low percentage is less than 10%) in order to obviate the rejection. Appropriate correction is required.
Claim Rejections - 35 USC § 102
15. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
16. Claim(s) 22-24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Szot et al. (J. Clin. Invest. 2018, 128(7): 2927-2943, IDS filed 11/4/22).
Szot et al. disclose the measurement of TEM8 and its expressed in tumor-associated fibroblasts, pericytes, and endothelium. While TEM8 was originally identified in tumor endothelial cells, subsequent studies revealed widespread TEM8 expression throughout the tumor stroma. To determine which stromal cell types expressed TEM8, the researchers performed co-IF staining on human colorectal tumors. TEM8 colocalized strongly with CAF markers, including FAP, a-smooth muscle actin (α-SMA), and PDGFRB (Figure 1C). While TEM8 was expressed in stromal cells throughout the tumor (Supplemental Figure 3), fibroblast expression was heterogeneous, with high levels detectable in some, but not all, FAP+, α-SMA+, and PDGFRB+ stromal cells. Therein teaching TEM8+FAP+ fibroblasts or ANTXR1+FAP+fibroblasts.
Although fibroblasts were the most prominent TEM8+ stromal cell type, in some tumors TEM8 was detectable in CD146+ endothelial cells (ECs) and desmin+ pericytes (Figure 1D and Supplemental Figure 4). See page 2929.
Claim Rejections - 35 USC § 103
17. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
18. Claims 22-25 and 37-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Szot et al. (J. Clin. Invest. 2018, 128(7): 2927-2943, IDS filed 11/4/22) in view of Ana Costa et at., CANCER CELL, vol. 33, no. 3, 1 March 2018 (2018-03-01), pages 463-479. IDS filed11/4/22) and Anne-Marie Givel et al., (NATURE COMMUNICATIONS, vol. 9, no. 1, 13 March 2018 (2018-03-13), IDS filed 11/4/22).
Szot et al. (J. Clin. Invest. 2018, 128(7): 2927-2943) discloses the measurement of TEM8 and its expressed in tumor-associated fibroblasts, pericytes, and endothelium. While TEM8 was originally identified in tumor endothelial cells, subsequent studies revealed widespread TEM8 expression throughout the tumor stroma. To determine which stromal cell types expressed TEM8, the researchers performed co-IF staining on human colorectal tumors. TEM8 colocalized strongly with CAF markers, including FAP, a-smooth muscle actin (α-SMA), and PDGFRB (Figure 1C). While TEM8 was expressed in stromal cells throughout the tumor (Supplemental Figure 3), fibroblast expression was heterogeneous, with high levels detectable in some, but not all, FAP+, α-SMA+, and PDGFRB+ stromal cells. Therein teaching TEM8+FAP+ fibroblasts or ANTXR1+FAP+fibroblasts.
Although fibroblasts were the most prominent TEM8+ stromal cell type, in some tumors TEM8 was detectable in CD146+ endothelial cells (ECs) and desmin+ pericytes (Figure 1D and Supplemental Figure 4). See page 2929.
Szot et al. do not teach the analyzes of a subset of CAF cells in their cancer analyses.
However, Costa et al. discloses the differentiation of cancer associated fibroblasts into different sub-groups. The researchers disclose that the CAF-S1 sub-group has immunosuppressive properties and also describes their importance in predicting cancer treatment (see first page, grey square with the title Significance; Discussion, last paragraph on page 476).
While, Givel et al. list a number of possible genes that are over-expressed in the CAF-S1 subgroup (see Table 2). In Givel ANTXR1 is listed twice as a marker that is over- represented compared to the CAF-S4 sub-group. Thus, starting from Givel, the skilled person facing the objective technical problem, would consider any of the genes listed in Givel to arrive at the solution proposed.
Therefore it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to add the CAF sub-group as taught by Costa et al. and Givel et al. to the cancer treatment measuring ANTXR1-FAP-Fibroblasts as exemplified by Szot et al. because Costa et al. disclosed that the CAF-S1 sub-group had immunosuppressive properties and described their importance in predicting cancer treatment (see first page, grey square with the title Significance; Discussion, last paragraph on page 476).
One skilled in the art would have been motivated to measure CAF in order to predict cancer treatment and increase treatment efficacy.
Absent evidence to the contrary the use of known treatment regimens as recited in claims 37-42 is deemed an obvious design choice previously taught by the prior art. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945); In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988).
Therefore it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the known cancer treatment agents as recited to treat a patient in need therein in order to prevent patient death.
Allowable Subject Matter
19. Claim 26 is 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.
20. For reasons aforementioned, no claims are allowed.
Remarks
21. References considered relevant but not relied on for rejections:
A. Chen et al. Cancer Res, 73(18), pages 5821-33, 2013
B. Chaudhary et al. Cancer Cell, 21, pages 212-226, 2/14/12
22. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lisa Cook whose telephone number is 571-272-0816. The examiner works a flexible schedule but can normally be reached on Monday, Thursday, and Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at telephone number 571-270-3505. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
Remsen
571-272-0816
5/31/26
/LISA V COOK/Primary Examiner, Art Unit 1642
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