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 .
1. Claims 61-79 as filed on November 19 , 2024 are pending and under consideration.
Information Disclosure Statement
2. The information disclosure statement filed June 30, 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the lined-out information referred to therein has not been considered.
Specification
3. The disclosure is objected to because of the following informalities: the αβhIL2 mutein sequences in paragraphs [0285-0286] on page 97 of the specification filed November 19, 2024 should be labeled with SEQ ID NO: 9.
Appropriate correction is required.
Claim Objections
4. Claim 74 is objected to because of the following informalities: the word “hyperprofroliferative” on line 8 should be spelled “hyperproliferative” . 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.
5. Claims 61-64 and 69-79 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.
The claims are drawn to contacting tissues samples with an αβhIL2 mutein for the production of TILs and cell products comprising TILs. The specification teaches that IL2 refers to naturally occurring IL-2 and that human IL2 is abbreviated hIL2. See p. 42-¶ 0117. The specification teaches that the term “mutein” is used to refer to a polypeptide comprising one or more modifications to the primary structure (e.g., amino acid insertions, deletions, substitutions and modifications at one or more sites) relative to the primary structure of the parent polypeptide from which it was derived. See p. 44-¶ 0128. However, the specification does not teach what an αβhIL2 mutein is or to what it is limited. It is not clear if an αβhIL2 mutein is different from other IL2 muteins or if it has a different binding activity to the IL2 receptor or its subunits as compared to other IL2 muteins or IL2. Thus, given that the scope of IL2 muteins encompassed by an αβhIL2 mutein is unclear and indefinite the claims that recite αβhIL2 mutein (directly or indirectly) without more definition are also indefinite. The claims will be interpreted to encompass any mutein of hIL2.
Claim 70 recites the limitation "the administration of the quantity of antigen activated T-cells to the subject" in part ii). There is insufficient antecedent basis for this limitation in the claim which does not refer to administration of a quantity of antigen activated T-cells to the subject.
Claim 70 recites the limitation "the isolated population of cells" in part iii). There is insufficient antecedent basis for this limitation in the claim which does not refer to an isolated population of cells.
Regarding claim 74, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 74 recites the broad recitations of lymphoblastic leukemia (ALL) and hyperproliferative scars, and the claim also recites B-lineage ALL and T-lineage ALL and keloid scars ,which are the narrower statement(s) of the limitations. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 75, the preamble is drawn to an ex vivo method of preparing a population of antigen activated T cells. However the claimed method produces an expanded cell population comprising activated TILs. Thus, it is unclear if the objective of the claimed method is to prepare a population of antigen activated T cells or produce an expanded cell population comprising activated TILs. Thus, the conflicting objective and result of the method makes the method of claim 75 indefinite.
Claim 76 recites the limitation "the cell product" in lines 1-2 There is insufficient antecedent basis for this limitation in the claim which does not refer to a cell product.
Claim 79 recites use of an αβhIL2 mutein ex vivo for the activation and expansion of antigen activated T-cells. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP 2173.05 (q). Thus claim 79 is indefinite because it does not set forth any steps involved in the processes of preparing.
Claim Rejections - 35 USC § 112
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.
6. Claims 62, 63 and 79 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 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. This is a new matter rejection.
New claims 62 and 63 are drawn to:
62. The method of claim 61, wherein the method further comprises a step of administering to the subject a therapeutically effective amount of a second αβhIL2 mutein prior to step (a) and/or after step (c), wherein the first and second αβhIL2 muteins are the same or different.
63. The method of claim 61, wherein the method further comprises the steps of: (i) administering to the subject a therapeutically effective amount of a αβhIL2 mutein prior to step (a); and (ii) administering to the subject a therapeutically effective amount of a αβhIL2 mutein following step (c), wherein each of the αβhIL2 muteins are the same; the αβhIL2 muteins administered in steps (i) and (ii) are the same; the αβhIL2 mutein administered in step (i) and used in step (c) are the same, or each of the αβhIL2 muteins are different αβhIL2 muteins.
Although the specification as filed teaches the use of a first αβhIL2 mutein ex vivo to prepare a polyclonal population of cells enriched for tumor antigen experienced T cells and administering the population of cells to a subject and administering to said subject a therapeutically effective amount of a second αβhIL2 mutein, wherein the first αβhIL2 mutein and second αβhIL2 mutein are the same or different (see ¶¶ 0026-0029 of the specification filed 11/19/2024), the specification does not teach administering to the subject a therapeutically effective amount of a second αβhIL2 mutein with activated TILs in the various orders claimed, e.g. prior to step (a). Thus, claims 62 and 63 are new matter.
Regarding claim 79, although the specification teaches various methods to induce proliferation and expand antigen activated T cells with an αβhIL2 mutein (See ¶¶ 0042-0043 of the specification filed 11/19/2024), the specification does not teach the generic method of use of a αβhIL2 mutein as claimed in claim 79. Thus, claim 79 is new matter.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
7. Claim 79 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See MPEP 2173.05 (q). and Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
8. Claims 77 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e. a natural product) without significantly more. The claim(s) recite(s) a cell product produced by the method of claim 75, which is a population of activated TILs. This judicial exception is not integrated into a practical application because the cell product is a population of activate TILs treated with an αβhIL2 mutein. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is simply drawn to the cell product.
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The recent Eligibility Guidance (2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance and 2018 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019) address the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions). “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception.
In Prong One of Step 2A it is determined if the claim recites a judicial exception. If the claim recites a judicial exception then Prong Two of Step 2A determines whether the claims recites additional elements that integrate the exception into a practical application.
If the answer to Prong Two of Step 2A is no, Step 2B is used to determine whether the claim as a whole amounts to significantly more than the exception by the recitation of additional elements.
The present claims are directed to a product so Step 1 is satisfied.
With respect to Step 2A MPEP 2106.04(c) II(C)(2) teaches:
In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e., the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). In sum, the claimed genes were different, but not markedly different, from their naturally occurring counterparts (the BRCA genes), and thus were product of nature exceptions.
In Ambry Genetics, the court identified claimed DNA fragments known as "primers" as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because "single-stranded DNA cannot be found in the human body". The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence. 774 F.3d at 760, 113 USPQ2d at 1243-44. The patentee also argued that the primers had a different function than when they are part of the DNA strand because when isolated as a primer, a primer can be used as a starting material for a DNA polymerization process. The court disagreed, because this ability to serve as a starting material is innate to DNA itself, and was not created or altered by the patentee:
In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction--a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here--the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.
Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, because the characteristics of the claimed primers were innate to naturally occurring DNA, they lacked markedly different characteristics from nature and were thus product of nature exceptions. A similar result was reached in Marden, where the court held a claim to ductile vanadium ineligible, because the "ductility or malleability of vanadium is . . . one of its inherent characteristics and not a characteristic given to it by virtue of a new combination with other materials or which characteristic is brought about by some chemical reaction or agency which changes its inherent characteristics". In re Marden, 47 F.2d 958, 959, 18 CCPA 1057, 1060, 8 USPQ 347, 349 (CCPA 1931
For Prong One of Step 2A the claim recites a judicial exception, i.e. a natural product which is a natural phenomenon. In particular, the claim recites a cell product produced by the method of claim 75, which is a population of activated TILs. So the answer to Prong One of Step 2A is yes the claims do recite a judicial exception.
For Prong Two of Step 2A the claims do not integrate the exception into a practical application. The judicial exception is not integrated into a practical application because the cell product is a population of activate TILs treated with an αβhIL2 mutein. This would produce TILs as they naturally respond to IL2. See Sim et al. (Cytokine & Growth Factor Reviews 25 (2014) 377–390), abstract § 2.1-IL-2, and Fig. 1. So the answer to Prong Two of Step 2A is no.
With respect to Step 2B MPEP 2106.05 (I) teaches that
The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)).
An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?") (emphasis added)); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"). Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
With respect to Step 2B MPEP 2106.05 (d) teaches that:
Another consideration when determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry.
If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.
. . .
On the other hand, Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 67, 101 USPQ2d 1961, 1964 (2010) provides an example of additional elements that were not an inventive concept because they were merely well-understood, routine, conventional activity previously known to the industry, which were not by themselves sufficient to transform a judicial exception into a patent eligible invention. Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79-80, 101 USPQ2d 1969 (2012) (citing Parker v. Flook, 437 U.S. 584, 590, 198 USPQ 193, 199 (1978) (the additional elements were "well known" and, thus, did not amount to a patentable application of the mathematical formula)). In Mayo, the claims at issue recited naturally occurring correlations (the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that a drug dosage will be ineffective or induce harmful side effects) along with additional elements including telling a doctor to measure thiopurine metabolite levels in the blood using any known process. 566 U.S. at 77-79, 101 USPQ2d at 1967-68. The Court found this additional step of measuring metabolite levels to be well-understood, routine, conventional activity already engaged in by the scientific community because scientists "routinely measured metabolites as part of their investigations into the relationships between metabolite levels and efficacy and toxicity of thiopurine compounds." 566 U.S. at 79, 101 USPQ2d at 1968. Even when considered in combination with the other additional elements, the step of measuring metabolite levels did not amount to an inventive concept, and thus the claims in Mayo were not eligible. 566 U.S. at 79-80, 101 USPQ2d at 1968-69.
Claim 75 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim is simply drawn to the cell product. Thus the cell product does not have a significanly different structure or function from the naturally TILs The absence of structural differences taken together with the lack of any functional difference between the claimed cell product and its natural counterparts demonstrates that the recited cell product is not markedly different from what exists in nature.
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.
9. Claim(s) 61, 62, 64, 65, 67, and 69-79 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020/131547 A1 (Chartier-Couraud et al. June 25, 2020), “Chartier”.
Regarding claims 61, 75, 76, 77 and 79, Chartier teaches a method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs comprising: (a) obtaining a first population of TILs from a tumor resected from a subject by processing a tumor sample obtained from the subject into multiple tumor fragments; (b) performing a priming first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, OKT-3, and optionally comprising antigen presenting cells (APCs), to produce a second population of TILs, wherein the priming first expansion is performed for a first period of about 1 to 7 days to obtain the second population of TILs, wherein the second population of TILs is greater in number than the first population of TILs; (c) performing a rapid second expansion by contacting the second population of TILs with a cell culture medium comprising orthogonal IL-2, OKT-3, and APCs, to produce a third population of TILs, wherein the rapid second expansion is performed for a second period of about 1 to 11 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs; (d) engineering the TILs to express orthogonal IL-2Rβ ; and (e) harvesting the therapeutic population of TILs obtained from step (d). See claims 1, 2, 130, and 215 and ¶ 1587.
Chartier teaches the orthogonal IL2 can be used in the methods and products of the inventions, is human IL-2 which contains mutations with respect to the wild type human IL2. See ¶¶ 1587-1595.
Chartier teaches that “ex vivo” refers to an event which involves treating or performing a procedure on a cell, tissue and/or organ which has been removed from a subject's body. See ¶ 0388. Thus, the above method performed on TILs from a tumor resected is an ex vivo method.
Regarding claims 61, 62, 72 and 75-79, Chartier teaches in claim 103:
A method for treating a subject with cancer, the method comprising administering expanded tumor infiltrating lymphocytes (TILs) comprising:
(a) obtaining a first population of TILs from a tumor resected from a subject by processing a tumor sample obtained from the subject into multiple tumor fragments;
(b) performing a priming first expansion by culturing the first population of TILs in a cell culture medium comprising IL-2, OKT-3, and antigen presenting cells (APCs) to produce a second population of TILs, wherein the priming first expansion is performed in a container comprising a first gas-permeable surface area, wherein the priming first expansion is performed for about 1 to 7 days to obtain the second population of TILs, wherein the second population of TILs is at least 50-fold greater in number than the first population of TILs;
(c) performing a rapid second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, OKT-3, and APCs, to produce a third population of TILs, wherein the number of APCs added to the rapid second expansion is at least twice the number of APCs added in step (b), wherein the rapid second expansion is performed for about 1 to 11 days to obtain the third population of TILs, wherein the third population of TILs is a therapeutic population of TILs, wherein the rapid second expansion is performed in a container comprising a second gas-permeable surface area;
(d) harvesting the therapeutic population of TILs obtained from step (c);
(e) engineering the TILs produced in step (d) to express orthogonal IL-2Rb;
(f) transferring the harvested TIL population from step (e) to an infusion bag;
(g) administering a therapeutically effective dosage of the TILs from step (f) to the subject; and
(h) administering a therapeutically effective dosage to the subject of an IL-2 ortholog capable of binding to said expressed orthogonal IL-2Rβ.
Chartier teaches the orthogonal IL2 can be used in the methods and products of the inventions, is human IL-2 contains mutations with respect to the wild type human IL2. See ¶¶ 1587-1595.
Chartier teaches that “ex vivo” refers to an event which involves treating or performing a procedure on a cell, tissue and/or organ which has been removed from a subject's body. See ¶ 0388. Thus, the above method performed on TILs from a tumor resected is an ex vivo method.
Regarding claims 65 and 67, Chartier teaches the orthogonal IL2 contains substitutions at position 22 of the IL2. See ¶¶ 1589, 1594, and 1596. Chartier teaches the orthogonal IL2 of SEQ ID NO: 133, which is identical to SEQ ID NO: 6 mutein of the instant specification, contains a mutation at position 22, which is 95% identical to SEQ ID NO: 4. See ¶¶ 0377 and Appendix.
Regarding claims 61, 64, 75, and 79, Chartier teaches that the production methods antigen activated and expand T cells in the TILs. See ¶¶ 0168, 0431-0438, p58- ¶ 0462 and ¶ 0559.
Regarding claims 69 and 73, Chartier teaches that the orthogonal IL-2 can be fused to the Fe domain of lgG, albumin, or other molecules to extend its half-life, e.g. by pegylation, glycosylation, and the like as known in the art. See ¶¶ 1599 and 1663.
Regarding claim 70, Chartier teaches that the tumor is a solid tumor and isolating TILs from whole blood or tumor digests. See ¶¶ 0107, 0120-0122, 0228 and 0458-0459.
Regarding claims 70, 71 and 73, Chartier teaches prior to administering a therapeutically effective dosage of TIL cells to the patient, a non-myeloablative lymphodepletion regimen can be administered to the patient. See ¶¶ 0107 and 0110-0111 and claim 106.
Regarding claims 73 and 76, Chartier teaches the orthogonal cytokine receptor IL2- Rb is inserted by a gammaretroviral or lentiviral method into the first population of TILs, second population of TILs, or harvested population of TILs, or combinations thereof. See ¶¶ 0834 and 0859.
Regarding claims 73 and 76, Chartier teaches the orthogonal IL-2 receptor is human CD122 with mutations at positions 133 and 134, including H133D and Y134F. See ¶¶ 1593 and 001597.
Regarding claim 74, Chartier teaches that the tumor is a solid tumor including breast cancer, ovarian cancer, lung cancer, bladder cancer, and melanoma. See ¶¶ 0107 and 0120-0122 and claims 113-123.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
10. Claim(s) 61-65, 67, and 69-79 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/131547 A1 (Chartier-Couraud et al. June 25, 2020), “Chartier”.
Chartier teaches as set forth above, but does not teach administering to the subject a therapeutically effective amount of a αβhIL2 mutein prior to step (a); isolating a tissue sample from the subject, the tissue sample comprising a population of TILs.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Chartier administering to the subject a therapeutically effective amount of a αβhIL2 mutein prior to isolating a tissue sample from the subject because Chartier teaches that the IL2 ortholog mutants can be used to expand and activate the TILs. Thus, one would have been motivated to administer the IL2 ortholog mutants prior to isolation of the TILs to expand the number of TILs obtained for production and stimulate an initial anti-tumor response in the patient.
11. Claim(s) 66 and 68 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/131547 A1 (Chartier-Couraud et al. June 25, 2020), “Chartier” as applied to claims 61-65, 67, and 69-79 above, and further in view of US 2021/0196796 A1 (Penaflor-Aspuria et al. July1, 2021), “Penaflor-Aspuria”.
Chartier teaches as set forth above, but does not teach using N-terminal deletion mutants of the IL2 ortholog mutants
Penaflor-Aspuria teaches using the IL2 ortholog mutants with N-terminal deletions for the treatment diseases including cancer and for the production of T cells and TILs. See claims 1, 24, and 29 and ¶¶ 0118, 0169, 0193, 0542, and 0570.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Chartier and Penaflor-Aspuria and use the IL2 ortholog mutants with N-terminal deletions of Penaflor-Aspuria in the methods of Chartier because Penaflor-Aspuria teaches using the IL2 ortholog mutants with N-terminal deletions for the treatment diseases including cancer and for the production of T cells and TILs. One would have been motivated to use the IL2 ortholog mutants of Penaflor-Aspuria TIL production and cancer treatment to optimize the TIL production and cancer treatment.
Conclusion
12. Claims 61-79 are rejected. No claims allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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/PETER J REDDIG/Primary Examiner, Art Unit 1646
Alignment of SEQ ID NO: 6 with SEQ ID NO: 133 of Chartier
Query Match 100.0%; Score 673; Length 133;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APTSSSTKKTQLQLSQLLVLLKAILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APTSSSTKKTQLQLSQLLVLLKAILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLE 60
Qy 61 EELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR 120
Qy 121 WITFCQSIISTLT 133
|||||||||||||
Db 121 WITFCQSIISTLT 133
BHY18155
ID BHY18155 standard; protein; 133 AA.
XX
AC BHY18155;
XX
DT 20-AUG-2020 (first entry)
XX
DE Human interleukin 2 (IL-2), SEQ ID 133.
XX
KW IL-2 protein; Interleukin-2 ligand; cancer; cell expansion; cytostatic;
KW immunotherapy; lymphocyte; prophylactic to disease; t-lymphocyte;
KW therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2020131547-A1.
XX
CC PD 25-JUN-2020.
XX
CC PF 12-DEC-2019; 2019WO-US065892.
XX
PR 19-DEC-2018; 2018US-0782330P.
XX
CC PA (IOVA-) IOVANCE BIOTHERAPEUTICS INC.
XX
CC PI Chartier-Courtaud C, Fardis M;
XX
DR WPI; 2020-57188N/055.
XX
CC PT Expanding tumor infiltrating lymphocytes (TILs) into therapeutic
CC PT population of TILs by performing priming expansion by culturing
CC PT population of TILs in cell culture medium, and harvesting therapeutic
CC PT population of TILs, and engineering TILs.
XX
CC PS Disclosure; SEQ ID NO 133; 516pp; English.
XX
CC The present invention relates to a novel method for expanding tumor
CC infiltrating lymphocytes (TILs) into a therapeutic population of TILs.
CC The method comprises: (a) obtaining a first population of TILs from a
CC tumor resected from a subject by processing a tumor sample obtained from
CC the subject into multiple tumor fragments; (b) performing a priming first
CC expansion by culturing the first population of TILs in a cell culture
CC medium comprising IL-2, OKT-3, and antigen presenting cells (APCs) to
CC produce a second population of TILs; (c) performing a rapid second
CC expansion by supplementing the cell culture medium of the second
CC population of TILs with IL-2, OKT-3, and APCs to produce a third
CC population of TILs, where the number of APCs added in the rapid second
CC expansion is at least twice the number of APCs; (d) harvesting the
CC therapeutic population of TILs; (e) engineering the TILs to express
CC orthogonal interleukin-2 receptor beta (IL-2R beta); and (f) transferring
CC the harvested and engineered TIL population to an infusion bag. The
CC invention further claims: (1) a method for treating a subject with cancer
CC ; (2) a therapeutic population of TILs made by the method; (3) a TIL
CC composition comprising the therapeutic population of TILs and a carrier
CC or a cryopreservation media; (4) a sterile infusion bag comprising the
CC TIL composition; (5) a cryopreserved preparation of the therapeutic
CC population of TILs; (6) a method for expanding T cells; and (7) a method
CC for producing a therapeutic population of lymphocytes. The tumor
CC infiltrating lymphocyte of the present invention is useful for preventing
CC and treating cancer. Note: SEQ ID NO: 136 is described in page 36 of the
CC specification, but no further sequence has been shown.
Alignment of SEQ ID NO: 4 with SEQ ID NO: 6 of the instant specification
Title: US-18-576-329-4
Perfect score: 680
Sequence: 1 APTSSSTKKTQLQLEHLLLD..........IVEFLNRWITFCQSIISTLT 133
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 133 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : US-18-576-329-6.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 644 94.7 133 1 US-18-576-329-6 METHODS AND COMPOS
ALIGNMENTS
RESULT 1
US-18-576-329-6
Query Match 94.7%; Score 644; DB 1; Length 133;
Best Local Similarity 95.5%;
Matches 127; Conservative 2; Mismatches 4; Indels 0; Gaps 0;
Qy 1 APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLE 60
|||||||||||||| ||: |: |||||||||||||||||||||||||||||||||||||
Db 1 APTSSSTKKTQLQLSQLLVLLKAILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLE 60
Qy 61 EELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNR 120
Qy 121 WITFCQSIISTLT 133
|||||||||||||
Db 121 WITFCQSIISTLT 133
Prosecution Insights