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 Invention group II, drawn to a method of treating a subject for cancer that is positive for a stromal marker, claims 16-18, in the reply filed on 08/25/2026 is acknowledged. New claims, 19-26, are considered under the invention group II.
Claim 1 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species/invention, there being no allowable generic or linking claim.
Applicant timely traversed the restriction (election) requirement in the reply filed on 08/25/2026.
The traversal is on the grounds that there is not a serious burden on the examiner to search all of the claims together, with reference to MPEP 803.
The requirement for the restriction of Inventions group I and group II is still deemed proper, because a special technical feature i.e., stromal marker was identified in the earlier filled restriction requirement, the said feature was shared between the restricted inventions, and the said technical feature did not make a contribution over prior art. Therefore, there’s no unity between the restricted groups, as the groups do not contain a special technical feature which contributes over the prior art. Also, the method requires materially different components other than the cell. A search of the cells would not necessarily overlap with a search of the method. Therefore, the restriction is made FINAL.
Claims 16, 18-26 are presented for examination on the merits.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/27/2026, 09/25/2025 and 01/17/2024 have been considered by the examiner.
Drawings
The drawings were received on 01/17/2024. These drawings are acceptable.
Foreign Priority
Receipt is acknowledged of a certified copy of foreign priority application 074489.
Claim Status
Claims 1, 16, 18-26 are pending
Claims 2-15 and 17 are cancelled
Claims 16, 18-26 are under examination
Claim objections.
Claim 16, element (a) recites “stomal antigen”. Appropriate spelling correction is required.
Claim 22 include periods before the end of the claim (e.g. “i.” in claim 22). Periods are only allowed at the end of a claim. Applicant is directed to MPEP 608.01(m) which states “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i).”
To overcome this objection to claim 22, it is recommended that Applicant amend all instances of periods before the end of the claim to parentheses (for example, “i.” in claim 22 would be amended to “i)” or “(i)”). Appropriate correction is required.
Claim 26, the acronyms are recited before the antigen names which are in parentheses. Usually, the acronyms are in parentheses following the name. Appropriate conventional recitation is requested.
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.
Claims 16,18- 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite.
Regarding claim 16, this claim recites “the stromal marker” under the wherein clause, a stromal marker was not previously recited in the claim. Therefore, the claim has insufficient antecedent basis and it is not clear what stromal marker is referred to by the claim as recited. Therefore, the claim is indefinite.
Regarding claim 18, this claim recites including thyroid in parenthesis. This appears to be a preferential example of a head and neck cancer. Therefore, it is not clear if the recited element inside parenthesis is a limitation of the claim or not. Therefore, the instant claim is indefinite for failing to clearly and distinctly point out the subject matter.
Regarding claim 25, the claim recites binding of the BTTS to FAR activates expression of IL-2 in the tumor. It is not clear how an immune cell comprising the circuit recited in claim 16 leads to expression of IL-2 in the tumor. Example given in specification page 35 recites IL-2 expression by the immune cell. Therefore, the claim is indefinite for failing to clearly point out the subject manner.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16, 18-26 are rejected under 35 U.S.C. 102(2) as being anticipated by US 20210023136, Lim et al., 2021, as evidenced by Lan et al., 2008 and Zhu at al., 2023
Regarding claim 16, Lim teaches a cancer treatment method comprising, administering a genetically modified immune cell (reads on engineered immune cell) (claim1), to a subject that has solid tumor (claim 6) expressing an antigen present on a stromal cell (0061) in the tumor microenvironment, wherein the said immune cell comprises a molecular circuit (abstract, claim 1) with the following components.
A) binding- triggered transcriptional switch (BTTS) that binds a priming antigen expressed in a priming cell (claim1 a), wherein in the priming cell is a stromal cell (0061).
a nucleic acid sequence encoding an antigen-specific therapeutic (claim 1b), wherein the antigen-specific therapeutic is secreted by the immune cell (claim 10), Lim also recites, in some instances the immune cell encoding the circuit of their disclosure may involve a non-limiting examples of cytokines of which the expression/ secretion can be modulated by the circuit, including IL-2 (0085, 0086) which is a pro-inflammatory cytokine as evidenced by Lan et al., 2008.
a nucleic acid sequence encoding an antigen-specific therapeutic (claim 1b), wherein the antigen-specific therapeutic is an immune receptor which is a chimeric antigen receptor (CAR) (claim 9), and the target killing by the immune cell is activated when the CAR is bound to the respective tumor antigen (Example 2: multi receptor circuits for IF/THEN gated T cell activation, 0272-0273).
Wherein in some instances activation of the immune cell through a circuit induces the expression of cytokines including pro-inflammatory cytokines such as IL-2 (0086), the circuit is activated when BTT is bound to its priming antigen (claim 1). CAR is either expressed or not expressed on the surface of the immune cells (claims 8 and 9), “NOT” gate may prevent the expression or activation of particular component of the circuit such as CAR (0237). The BTT containing immune cells or the CD8+ synNotch AND-gate T cells first sense the corresponding surface antigen via their respective BTTs (i.e., synNotch receptor) which then induces the expression of the corresponding CAR in order to target the cells expressing the CAR binding antigens (Example 2: multi receptor circuits for IF/THEN gated T cell activation, 0272-0273). Therefore Lim reads on the limitations recited under the wherein clause.
Regarding claim 18, Lim teaches examples of treatable cancers that present priming cells to activate the BTT circuit such as breast cancer, prostate cancer, pancreatic cancer, lung cancer, colorectal cancer, and ovarian cancer (0063).
Regarding claim 19, Lim teaches that the treatment may involve the expression of cytokines including but not limited to IL-2, IL-12,IL-7, IL-15 (0086).
Regarding claim 20, Lim teaches that the specificity of BTTS is determined by the specific binding member of the extracellular domain (0177), and the said specific binding member is an antibody such as a single chain FV (scFV)(0179) or nanobody (0026)which binds to stromal antigen (0061, claim 1a).
Regarding claim 21, Lim teaches the SynNotch BTTS (0188) which comprises an intracellular domain (0189 b) wherein in useful BTTS’s the functional intracellular domain is a transcription factor (0185, fig 1C). Binding of SynNotch induces the cleavage of SynNotch at one or more proteolytic cleavage sites, thereby releasing the intracellular domain that triggers the production of an encoded payload. Depending on the context, the said payload is expressed on the cell surface (0189), an example of a SynNotch with binding triggered expression of CAR immune receptor is shown in fig.1C. In some instances pay load induced by binding of BTTS to its respective priming antigen (0134), i.e., a stromal antigen in some instances(0061) include a secreted therapeutic (claim 10), in some instances the said secretion is a cytokine (0087), such as IL-2 (0086) which is pro-inflammatory, as evidenced by Lan et al., 2008
Regarding claim 22, Lim teaches that BTT comprises
an extracellular domain comprising a specific binding member (0189), BTTs binds a priming antigen expressed in a priming cell (claim1 a), wherein in the priming cell is a stromal cell (0061).
a transmembrane domain (0185)
binding of the specific binding member induced cleavage of the of SynNotch (an example of BTT, according to claim) at one or more proteolytic cleavage sites (0189).
binding of the specific binding member induce synNotch cleavage that release the intracellular domain which triggers the production of an encoded payload. In some instances pay load is induced by binding of BTTS to its respective priming antigen (0134), i.e., a stromal antigen (0061) include a secreted therapeutic (claim 10), in some instances the said secretion is a cytokine (0087), such as IL-2 (0086) which is pro-inflammatory, as evidenced by Lan et al., 2008.
In addition, BTT binding to its priming antigen (i.e., stromal marker) activates the expression of an antigen-specific therapeutic (claim1), wherein the antigen-specific therapeutic is CAR or Tcell receptor (claims 8 and 9). Lim also provide non-limiting examples of “IF/THEN” (0239) and ”NOT” gates involving CAR (an immune receptor) expression, wherein CAR is either expressed or not expressed on the surface of the immune cells( claims 8 and 9). Therefore, Lim reads on “transcriptional activator inducing the expression of immune receptor if the immune receptor is not constrictively expressed”.
Regarding claim 23, Lim teaches that the immune cell/ host cell is a cytotoxic T cell (0228, 0205).
Regarding claim 24, Lim teaches the immune receptor to be CAR or TCR (claims 9, 44).
Regarding claim 26, Lim teaches that BTTS binds a priming antigen expressed in a priming cell (claim1 a), wherein in the priming cell is a stromal cell (0061). Lim also teaches the priming/targeting antigen CDHII (0077), and a non-limiting examples of cancer associated antigens including PDGFR (0128). PDPN and LRRC15 are stromal marker/antigens as evidenced by Zhu at al., 2023. Therefore, Lim teaches the requisite limitations of claim 26.
Therefore, the reference anticipates the claimed invention.
Conclusion
No claim is allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HASHANTHI ABEYRATNE-PERERA whose telephone number is (571)272-6562. The examiner can normally be reached Monday-Friday 7:30 am- 5:00pm.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/ Examiner, Art Unit 1632
/PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632
