DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of group I, claims 1-11, in the reply filed on 3/20/26, is acknowledged. Upon reconsideration, the species election requirement as to a species of agonist is withdrawn., Claims 12 and 15-19 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1-11 are being acted upon.
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 1-11 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.
Claim 1 recites the limitation ""the anti-cancer effect" in line 1. There is insufficient antecedent basis for this limitation in the claim
Claims 6-7 recite the limitation “the GCN2 pathway agonist” in line 1. There is insufficient antecedent basis for this limitation in the claims. Additionally, claims 6-7 are unclear since they recite that the agonist is added immediately, or within two weeks following “isolation of the T cell population”. However, claim 1, from which the claims depend, does not recite a step of “isolation”, rendering the claims unclear and indefinite.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-3, 6-7, 9-11 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(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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of environments or agonists that activate the GCN2 pathway.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP 2163.
The instant claims are directed to a method for improving the anti-cancer effect of T cells comprising culturing the T cells in an environment that activates the GCN2 pathway, such as by including a GCN2 pathway agonist. This broadly encompasses a genus of structurally and functionally distinct conditions and agonists. For example, the claims would encompass conditions or agonists that act on GCN2 itself, or any other molecule in the GCN2 pathway. The claims would encompass structurally and functionally distinct conditions or agonists, such as peptides, small molecules, nucleic acids, or antibodies. The state of the art is such that GCN2 is extremely complex and can be induced by a variety of stress responses, and building a model for GCN2 activation is fraught with difficulty (see Masson, 2019). See also Gold, 2022, which teaches that the GCN2 pathway can be activated by a variety of stresses, but that the effect on cells can range from apoptosis to proliferation and it is dependent on the stress type, length, intensity and other factors. The specification does not disclose a correlation between structure and function, nor does it disclose a representative number of species. The only species of conditions disclosed are culture under amino acid starvation or with GCN2 the specific chemical compounds recited in claims 4-5. These are not sufficiently representative of the broad genus of different agonists and environments encompassed by the present claims. For example, the present claims would encompass nucleic acid or peptide agonists, but none are disclosed. The present claims would encompass conditions and agents that act on numerous distinct downstream GCN2 pathway signaling molecules but none are disclosed.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of antibodies and inhibitors encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002).
In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
Claims 1-3, 5-7, 9-11 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:
A method for improving the anti-cancer effect of T cells comprising culturing the T cells with a GCN2 pathway agonist, wherein the agonist is halofuginone, or comprising culturing the T cells in an environment that is amino acid deficient or depleted;
does not reasonably provide enablement for:
A method for improving the anti-cancer effect of T cells comprising culturing the T cells in an environment that activates the GCN2 pathway.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
The instant claims are directed to a method for improving the anti-cancer effect of T cells comprising culturing the T cells in an environment that activates the GCN2 pathway, such as by including a GCN2 pathway agonist. This broadly encompass a genus of structurally and functionally distinct conditions and agonists. For example, the claims would encompass conditions or agonists that act on GCN2 itself, or any other molecule in the GCN2 pathway. The claims would encompass structurally distinct conditions or agonists, such as peptides, small molecules, nucleic acids, or antibodies. . The state of the art is such that GCN2 is extremely complex and can be induced by a variety of stress responses, and building a model for GCN2 activation is fraught with difficulty (see Masson, 2019). See also Gold, 2022, which teaches that the GCN2 pathway can be activated by a variety of stresses, but that the effect on cells can range from apoptosis to proliferation and it is dependent on the stress type, length, intensity and other factors. Furthermore, while certain compounds such as halofuginone act as GCN2 agonists, other structurally related compounds, such as MAZ1310 and MAZ1442, lack activity in cell based assays (see Keller, 2012, of record).
Thus, based on the unpredictability of the art and the breadth of the claims, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the instant claims. The instant specification discloses culturing T cells with halofuginone, or under conditions of amino acid starvation. However, no examples or guidance are provide for practicing the method using any other conditions that activity the GCN2 pathway or using any other agonist. Thus, based on the unpredictability of the art, the breadth of the claims, and the lack of guidance provided by the instant specification, it would require undue experimentation to practice the full scope of the claimed method.
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.
Claim(s) 1-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated WO 2010/019210 (of record).
WO 2010/019210 teaches a method comprising providing a population of T cells and culturing the population of T cells with the GCN2 pathway agonist halofuginone, which activates GCN2 (See, paragraphs 55, 529, 531, 550-552, for example). WO 2010/019210 teaches adding halofuginone to the culture immediately following isolation of the T cell population (see paragraph 531, 550-552 and 55, in particular). WO 2010/019210 teaches an embodiment wherein T cells are cultured in a medium that is amino acid depleted or deficient (see paragraph 59, in particular). WO 2010/019210 teaches culturing CD8 T cells (See paragraph 68, 96 Fig. 5, and 10 in particular). The method would inherently improve the “anti-cancer” effect of the T cells, since it is identical to the claimed method. Regarding claim 5, it is noted that WO 2010/019210 also teaches culturing the T cells with MAZ1310, which anticipates the claim.
Claim(s) 1, 8-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vodnala, 2019.
Vodnala teach a method of culturing T cells to increase “stemness” and multipotency, comprising providing a T cell population and culturing the T cells in the presence of elevated extracellular potassium (see entire document). Vodnala teaches that doing so results in a starvation response with depletion of amino acid uptake, i.e. an environment that is amino acid deficient. Thus, the conditions of Vodnala are inherently an environment that activates the GCN2 pathway. Vodnala teach culturing CD8 T cells and culturing TIL (See page 6, in particular). Vodnala teach that the method is an important strategy for improving T cell based immunotherapy for cancer and improve anti-tumor function (i.e. improving the anti-cancer effect of T cells, see page 11, in particular).
Claim(s) 1, 8-11 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 2021/0332326, as evidenced by Vodnala, 2019.
The ‘326 publication teaches teach a method of improving anti-cancer effect of T cells comprising providing a T cell population and culturing T cells in the presence of elevated extracellular potassium. As evidenced by, Vodnala doing so results in a starvation response with depletion of amino acid uptake, i.e. an environment that is amino acid deficient and thus inherently an environment that activates the GCN2 pathway. The ‘326 publication teaches culturing CD8 T cells, TIL, or CAR-T cells (See paragraph 10 and 138, in particular).
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.
Claim(s) 1, 8-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vodnala, 2020, in view of Alizadeh, 2019.
The teachings of Vodnala are described above.
The reference differs from the claimed invention in that it does not explicitly teach culturing CAR T cells.
Alizadeh teaches culture of CAR-T cells and that methodologies that increase their stemness and anti-tumor activity are important for adoptive T cell therapies.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use CAR T cells, as taught by Alizadeh, as the T cells for culture in the method of Vodnala. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Alizadeh teaches culture of CAR-T cells and that methodologies that increase their stemness and anti-tumor activity are important for adoptive T cell therapies.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
.
Prosecution Insights