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 .
Claim status
In the reply on 30 October 2025 Applicant has amended claims 4-14 and 16. Therefore, claims 1-20 are herein pending.
Election/Restrictions
Applicant elected without traverse of species heat shock protein for damage-associated molecular pattern (DAMP) and vascular endothelial growth factor (VEGF) for regenerative activity. Claims 1-5, 7-8, and 16 read on the above species.
Claims 6, 9-15, and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Claims 1-5, 7-8, and 16 are herein under examination.
Priority
This application was filed 12/16/2022, which claims Priority from Provisional Application 63297883 filed on 01/10/2022. Thus, the earliest possible priority for the instant application is 01/10/2022.
Information Disclosure Statement
No information disclosure statement (IDS) has been submitted.
Applicant is reminded that 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.
Drawing
The subject matter of this application admits of illustration by a drawing to facilitate understanding of the invention: “the method of making a chimeric antigen receptor (CAR) molecule for CAR T cell. In here, the illustration of CAR will highlight the nature of the CAR composition. The drawing of CAR is sought to be patented without its being necessary for the understanding of the CAR composition. Therefore, Applicant needs to provide the illustration of CAR composition, as required to furnish a drawing under 37 CFR 1.81(c). No new matter may be introduced in the required drawing. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d).
Objection to the Specification
This specification is objected to because the application did not provide proper antecedent basis for the term “damage-associated molecular pattern”. SPEC specifies danger associated molecule is a DAMP. MPEP 2173.03 states that “The specification should ideally serve as a glossary to the claim terms so that the examiner and the public can clearly ascertain the meaning of the claim terms. Correspondence between the specification and claims is required by 37 CFR 1.75(d)(1), which provides that claim terms must find clear support or antecedent basis in the specification so that the meaning of the terms may be ascertainable by reference to the specification. If the specification does not provide the needed support or antecedent basis for the claim terms, the specification should be objected to under 37 CFR 1.75(d)(1). See MPEP § 608.01(o) and MPEP § 2181, subsection IV. Applicant will be required to make appropriate amendment to the description to provide clear support or antecedent basis for the claim terms provided no new matter is introduced, or amend the claim.”
In here, the “damage-associated molecular pattern” doesn’t have clear support or antecedent basis in the specification. Therefore, appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
(Written description)
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 1-5, 7-8, and 16 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 contains subject matter that 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 pre-AIA the inventor, at the time the application was filed, had possession of the claimed invention.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
REQUIREMENTS TO ESTABLISH ACTUAL REDUCTION TO PRACTICE
"In an interference proceeding, a party seeking to establish an actual reduction to practice must satisfy a two-prong test: (1) the party constructed an embodiment or performed a process that met every element of the interference count, and (2) the embodiment or process operated for its intended purpose." Eaton v. Evans, 204 F.3d 1094, 1097, 53 USPQ2d 1696, 1698 (Fed. Cir. 2000).
The same evidence sufficient for a constructive reduction to practice may be insufficient to establish an actual reduction to practice, which requires a showing of the invention in a physical or tangible form that shows every element of the count. Wetmore v. Quick, 536 F.2d 937, 942, 190 USPQ 223, 227 (CCPA 1976). For an actual reduction to practice, the invention must have been sufficiently tested to demonstrate that it will work for its intended purpose, but it need not be in a commercially satisfactory stage of development. See, e.g., Scott v. Finney, 34 F.3d 1058, 1062, 32 USPQ2d 1115, 1118-19 (Fed. Cir. 1994) (citing numerous cases wherein the character of the testing necessary to support an actual reduction to practice varied with the complexity of the invention and the problem it solved). If a device is so simple, and its purpose and efficacy so obvious, construction alone is sufficient to demonstrate workability. King Instrument Corp. v. Otari Corp., 767 F.2d 853, 860, 226 USPQ 402, 407 (Fed. Cir. 1985).
For additional cases pertaining to the requirements necessary to establish actual reduction to practice see DSL Dynamic Sciences, Ltd. v. Union Switch & Signal, Inc., 928 F.2d 1122, 1126, 18 USPQ2d 1152, 1155 (Fed. Cir. 1991) ("events occurring after an alleged actual reduction to practice can call into question whether reduction to practice has in fact occurred"); Fitzgerald v. Arbib, 268 F.2d 763, 765-66, 122 USPQ 530, 531-32 (CCPA 1959) ("the reduction to practice of a three-dimensional design invention requires the production of an article embodying that design" in "other than a mere drawing"); Birmingham v. Randall, 171 F.2d 957, 80 USPQ 371, 372 (CCPA 1948) (To establish an actual reduction to practice of an invention directed to a method of making a product, it is not enough to show that the method was performed. "[S]uch an invention is not reduced to practice until it is established that the product made by the process is satisfactory, and [ ] this may require successful testing of the product."). See MPEP 2138.05.
Claim 1 is broadly drawn to a method of making a regenerative chimeric antigen receptor (CAR) T cell, wherein the CAR has binding affinity for the genus of molecules associated with tissue injury and capable of inducing expression of the genus of molecules possessing regenerative activity. However, the disclosure as originally filed does not provide adequate written description support for the full breadth of the invention as presently claimed.
The specification discloses a method of making a CAR T cell comprising a CAR molecule having affinity for a danger associated molecular pattern (DAMP) such as membrane bound vimentin, heat shock protein, membrane calreticulin, thrombin, troponin, tissue factor, extrinsic factor, complement activator (see SPEC [0027]-[0029], [0031]-[0036]¶). The CAR-T cell is capable of producing a regenerative signal upon activation is a gene element which encodes a molecule or series of molecules that are secreted and the gene element is activated by a specific promoter associated with activation of the population of immune cells, wherein the activators, see SPEC [00131]. Therefore, SPEC has specific adequate support for specific molecules associated with tissue injury.
Furthermore, the specification discloses that the CAR is capable of inducing expression of the IL-3,IL-4, IL-5, IL-10, IL-13, IL-20, Il-35, IL-37, TGF-[Symbol font/0x61] and [Symbol font/0x62], RGF, IGF-1, HGF-1, VEGF, PDGF, PDGF-BB, FGF-1, FGF-2, …CTGF, activin, Galectin1-15, epigen, melanocyte stimulating factor, MIP-1-[Symbol font/0x61] and [Symbol font/0x62], and GDF-11 (see SPEC [0037]-[0077]¶) are possessing regenerative activity. Therefore, CAR is only capable of inducing expression of specific molecules possessing regenerative activity. However, the specification does not show any embodiments that meet all the limitations of the claim reduced to practice. Therefore, an actual reduction to practice of an invention directed to a method of making a product is not established at the time of filling. The successful testing of the product of the current invention is not shows reduced to practice, therefore, it is not established that the product made by the process is satisfactory. See MPEP 2163(I)-(II) and 2163.02.
Therefore, the specification fails to adequately describe the full scope of claim 1. The specification supports only a narrow scope of the inventive concept as described in above, but does not provide support for the full scope of the method of making CAR T cells, wherein the CAR has an antigen binding domain that binds to any molecule associated with tissue injury, nor for a CAR that is capable of inducing expression of any molecule possessing regenerative ability.
In the prior art Abbot et al., (US20160030479A1; published on Feb. 4, 2016; cited in PTO892; hereinafter “Abbot”) provides genetically modified cells, (i.e., T lymphocytes, e.g., human T lymphocytes), that comprise polypeptide polypeptides can, for example, be important for a drug product comprising a cell therapeutic, e.g., a chimeric antigen receptor-expressing CAR T lymphocytes [0005-0006]. The CAR having an antigen binding domain (scFvs) [0089] that binds to a damage to normal tissue (associated with tissue injury), causing the release of molecules known as damage-associated molecular pattern molecule (DAMP) [0090]. Therefore, the antigen is a DAMP, wherein DAMP is a heat shock protein (HSP70) [0088]. Furthermore, Abbot discloses that the CAR associated with inducing expression of vascular endothelial growth factor (VEGF) [0090]. Furthermore, Abbot showing successful testing of the product shows reduced to practice, wherein individual is monitored for two weeks afterwards to establish a reduction of at least 90% ofCD19+ B cells in the individual's blood [0132]-[0135], therefore, reduction to practice of the product made by the process is satisfactory.
Therefore, an actual reduction to practice of instant invention directed to a method of making a product is not established at the time of filling and POSITA cannot predictably identify a method that exercise in this invention of making a regenerative chimeric antigen receptor (CAR) T cell, wherein the CAR is comprising binding capability to DAMP associated with tissue injury and regenerative capability that exercise in this invention.
The Examiner concludes that there is insufficient written description of the instantly claimed genus of method of making a regenerative chimeric antigen receptor (CAR) T cell, wherein the CAR is comprising binding capability to DAMP associated with tissue injury and regenerative capability. Specifically, doesn't have an adequate written description on actual reduction to practice of instant invention directed to a method of making a product is not established at the time of filling. The successful testing of the product of the current invention is not shows reduced to practice, therefore, it is not established that the product made by the process is satisfactory. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed in claim 1 and dependent claims 2-5, and 7-8.
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 1-5, 7-8, 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 and 16 are indefinite because the term “regenerative activity”. The instant specification does not specifically define the “regenerative activity” and there is no apparent art-recognized definition for the term. Therefore, POSITA at the time of the invention would not know encompasses the capability of inducing expression of a molecule possessing “regenerative activity”. See MPEP 2173.05(b). Dependent claims 2-5, 7-8 are rejected as being dependent upon rejected base claim 1.
The term “molecule associated with regenerative activity” in claim 16 is indefinite for insufficient antecedent basis. It should be “molecule possessing regenerative activity”. Obviously, however, the failure to provide explicit antecedent basis for terms does not always render a claim indefinite. If the scope of a claim would be reasonably ascertainable by those skilled in the art, then the claim is not indefinite. See MPEP 2173.05(e).
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.
Anticipated by Abbot et al.
Claims 1-5, 7-8 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Abbot et al., (US20160030479A1; published on Feb. 4, 2016; cited in PTO892; hereinafter “Abbot”).
With respect to claims 1, 5, 7, 8, and 16 Abbot provides genetically modified cells, (i.e., T lymphocytes, e.g., human T lymphocytes), that comprise polypeptide polypeptides can, for example, be important for a drug product comprising a cell therapeutic, e.g., a chimeric antigen receptor-expressing CAR T lymphocytes [0005-0006]. The CAR having an antigen binding domain (scFvs) [0089] that binds to a damage to normal tissue (associated with tissue injury), causing the release of molecules known as damage-associated molecular pattern molecule (DAMP) [0090]. Therefore, the antigen is a DAMP, wherein DAMP is a heat shock protein (HSP70) [0088]. Furthermore, Abbot discloses that the CAR associated with inducing expression of vascular endothelial growth factor (VEGF) [0090].
With respect to claims 2, 3, and 4, Abbot teaches that the cell possesses a transmembrane domain, a costimulatory signaling region, and optionally an intracellular signaling domain (i.e., CD3 zeta signaling domain) [0096], wherein a costimulatory molecule is selected from CD28, 4-1BB and OX40 [0134].
Accordingly, Abbot anticipates the instant claims 1-5, 7-8 and 16.
Anticipated by Frost et al.
Claims 1-5, 7-8 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frost et al., (US 20210317408A1; published on Oct. 14, 2021; cited in PTO892; hereinafter “Frost”), evidentiary reference Jentho et al. (Frontiers in immunology, 12, p.699563, cited in PTO892; hereinafter “Jentho”).
With respect to claims 1, 5, 7, 8, and 16 Frost provides a method and composition for genetically modifying lymphocyte (i.e., T cell) that express chimeric antigen receptor (CAR) [0010], having an antigen binding domain that binds to a damage associated molecular pattern molecule (DAMP) [0219]; wherein said DAMP is membrane heat shock protein (e.g., HPS70 or HPS90 [0421]).
Furthermore, Frost discloses that the CAR capable of inducing expression of vascular endothelial growth factor (VEGF) [0157-0158], [0210-0213].
Although Frost does not specifically disclose that antigen binding domain binds to a molecule (i.e., DAMP) associated with tissue injury, only discloses that CAR has affinity to binds DAMP. In the evidentiary reference Jentho et al. discloses the inherent property of the DAMP that is exposed during, after, or because of disrupted cellular homeostasis such as damage or injury (p. 4 Table 1 of Jentho). Therefore, Frost anticipates the CAR molecule with antigen binding domain binds to DAMP is associated with tissue injury. See MPEP 2131.01 and MPEP 2112 (ii) for case law on inherency. Therefore, this disclosure is considered to read on claims 1 and 5.
With respect to claims 2, 3, and 4, Frost teaches that the cell possesses a transmembrane domain, a costimulatory signaling region, and optionally an intracellular signaling domain (i.e., CD3 zeta signaling domain) [0313], wherein a costimulatory molecule is selected from OX40 and CD28 [0310].
Accordingly, Frost anticipates the instant claims 1-5, 7-8 and 16.
Pertinent References
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure is the following:
Frost et al. US20200397821A1 Pub. Date: Dec. 24, 2020) provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells with the CAR gene vector [0005], wherein, a polypeptide binds a damage associated molecular pattern molecule (DAMP) [0237].
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684