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 37, 38 and 47-64 as filed in the preliminary amendment filed February 09, 2024 are pending and under consideration.
Priority
2. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of November 02, 2023 for claims 37, 38 and 47-64 because the claims as currently constituted recite “A kit for treating multiple myeloma, comprising (a) a unit dosage of a T cell expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a hydrophobic portion disposed between an extracellular component and an intracellular component, wherein the extracellular component comprises a BCMA-specific binding domain, and (b) a unit dosage of a γ-secretase inhibitor” and a review of the parent applications does not reveal the claimed kit with a unit dosage of a T cell expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a hydrophobic portion disposed between an extracellular component and an intracellular component, wherein the extracellular component comprises a BCMA-specific binding domain. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
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.
3. Claims 37, 38 and 47-64 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.
Claims 37, 38 and 47-64 as amened in the preliminary amendment of February 09, 2024 are drawn to “A kit for treating multiple myeloma, comprising (a) a unit dosage of a T cell expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a hydrophobic portion disposed between an extracellular component and an intracellular component, wherein the extracellular component comprises a BCMA-specific binding domain, and (b) a unit dosage of a γ-secretase inhibitor”
A review of the specification as filed reveals support for “A kit for treating a hematologic and/or autoimmune disease or disorder, comprising (a) a unit dosage of a BCMA-specific binding protein, and (b) a unit dosage of a γ-secretase inhibitor.“ See original claim 37. However, this does not provide support for “A kit for treating multiple myeloma, comprising (a) a unit dosage of a T cell expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a hydrophobic portion disposed between an extracellular component and an intracellular component, wherein the extracellular component comprises a BCMA-specific binding domain . . .” because a unit dosage of “a T cell expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a hydrophobic portion disposed between an extracellular component and an intracellular component, wherein the extracellular component comprises a BCMA-specific binding domain” is distinct from “a unit dosage of a BCMA-specific binding protein” because it has a distinct structure and function from the BCMA CAR T cell now claimed.
Thus, claims 37, 38 and 47-64 as amened in the preliminary amendment of February 09, 2024 do not have adequate descriptive support in the specification and claims as filed and are 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.
4. Claims 37, 38, 47-52, and 54-56 are 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 unit dosage of a γ-secretase inhibitor, which includes natural products like a nicastrin-specific binding protein. This judicial exception is not integrated into a practical application because the γ-secretase inhibitor can be an individual component of the kit that is not combined with the other kit components. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the kit itself is routine way in the art to package therapeutics and does not change the structure of γ-secretase inhibitor.
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 claims recite a judicial exception, i.e. a natural product which is a natural phenomenon. In particular, the claims recite a γ-secretase inhibitor, which includes natural products like a nicastrin-specific binding protein. In particular, Hur et al. (Exp Mol Med 54, 433–446 (2022)) teach that nicastrin is bound by the natural proteins Aph-1 and Pen-2 in the g-secretase complex. See p. 446-both columns and Fig. 3b. Thus the a γ-secretase inhibitor, which includes natural products like a nicastrin-specific binding protein as claimed, includes naturally occurring proteins. 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 γ-secretase inhibitor can be an individual component of the kit that is not combined with the other kit components and kit itself is routine way in the art to package therapeutics and does not change the structure of γ-secretase inhibitor. For example, the FDA (CPG Sec 430.100 Unit Dose Labeling for Solid and Liquid Oral Dosage Forms, February 1984) teaches that drugs are routinely packaged in a “unit dose” form for the delivery of a single dose that protects the integrity of the dosage until the actual moment of administration. See Background-1st paragraph. 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)).
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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.
Additionally MPEP 2106.05 (d) II teaches that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
The additional limitation of a kit comprising the γ-secretase inhibitor in a unit dosage is routine way in the art to package therapeutics (see FDA, supra) and does not change the structure of γ-secretase inhibitor. Thus the claimed a unit dosage of a γ-secretase inhibitor includes natural products like a nicastrin-specific binding protein that do not have a significanly different structure or function from the naturally occuring proteins. The absence of structural differences taken together with the lack of any functional difference between the claimed γ-secretase inhibitor, like a nicastrin-specific binding protein, and their natural counterparts demonstrates that the recited products are 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.
5. Claim(s) 37, 47, 49-53 and 55-64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2019/090364 A1 (Green et al. May 09, 2019), “Green”.
Green teaches kits comprising BCMA CAR T cells and g-secretase inhibitors in unit doses for treatment of multiple myeloma. See abstract, ¶¶ 0003, 0005, 0047, 0090-0098, 0102-0106 and 0115-0117.
Green teaches the BCMA CAR binding domain is a scFv. See ¶¶ 0016, 0200, 0331 and 0333.
Green teaches the CARs contain transmembrane domains comprising hydrophobic regions that separates extracellular binding domain and the intracellular signaling domain. See ¶¶ 0334, 0385 and 0386.
Green teaches the CARs can comprise a CD3z intracellular signaling domain and CD28 and/or 4-1BB costimulatory intracellular signaling domains. See ¶¶ 0052. 0087, and 0104.
Green teaches the CARs can comprise hinges from IgG, CD8 (cluster of differentiation 8) or CD28 (cluster of differentiation 28) . See ¶¶ 0378-0382.
Green teaches the CARs can comprise spacer domains of about 12 amino acids or about 10 to 100 amino acids or any integer length in the ranges. See ¶¶ 0379.
Green teaches the T cells can be CD4+ or CD8+ T cells. See ¶¶ 0055, 0089, and 0105.
Green teaches the g-secretase inhibitors can be small molecule inhibitors like LY411575, DAPT, and compound 1. See ¶¶ 0082, 0113, and 0269-0270 and p. 209.
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.
6. Claim(s) 37, 38, 47, 49-53 and 55-64 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/090364 A1 (Green et al. May 09, 2019), “Green”.
Green teaches as set forth above.
Green additionally teaches administering lymphodepleting chemotherapy before administration of the CAR-T cells. ¶¶ 0062 and 0179.
Green teaches the formulations of the invention can include chemotherapeutic agents. See ¶¶ 0205 and 0208.
Green teaches additionally administering the cytokine IL-2 as part of the immunotherapy. See ¶ 0187.
Although Green does not teach placing the chemotherapeutic agents or IL-2 in the kit, 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 Green and add the chemotherapeutic agents or IL-2 to the kits of Green because Green teaches using these agents for therapy. One would have been motivated to put the therapeutic agents of Green in the kits of the invention for convenience, consistency, and/or for the purpose of commercial sale.
7. Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/090364 (Green et al. May 09, 2019), “Green” as applied to claims 37, 38, 47, 49-53 and 55-64 above, and further in view of US 2016/0046724 A1 (Brogdon et al. Feb. 18, 2016, IDS), “Brogdon”.
Green teaches as set forth above, but does not teach that the BCMA CAR comprises a scFv from the C11D5.3, C12A3.2, or C13F12.1 antibody
Brogdon teaches anti-BCMA CARs to be expressed in T cells or NK cells for the treatment of multiple myeloma, lymphoma, lung cancer and breast cancer. See abstract, ¶¶ [0003], [0005] and [0190].
Brogdon teaches that the BCMA CAR binding domains comprises a scFv. See [0006] and [0009].
Brogdon teaches that the BCMA CAR scFv domain is derived from the C11D5.3, C12A3.2, or C13F12.1 antibody. See ¶¶ [0085], [0086], [0311]-[0317], Tables 1, 16, 20, 21, 23 and 25.
Brogdon teaches the CAR comprises transmembrane domains selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154. See ¶¶ [0011], [0349] and [0363-0368]. The transmembrane domains like that of CD8 are hydrophobic. See ¶¶ [0349] and [0368].
Brogdon teaches the CAR comprises CD3z, CD28, 4-1BB, and/or OX40 signaling domains. See ¶¶ [0013]-[0020] and [0349].
Brogdon teaches the CAR comprises hinge domains from CD8, IgG, IgG4, and IgD containing a CH2 and CH3 hinge region. See ¶¶ [0012], [0349], [0365]-[0367], and [0634].
Brogdon teaches using naive, CD4+, and CD8+ T cells for generation of CAR T cells. See ¶¶ [0137], [0529], and [1089] and Fig. 19.
Brogdon teaches the BCMA CARs T cells kill multiple myeloma cells in vitro and in vivo. See Example 13 and Figs. 39A-C and 40A-C.
Brogdon teaches making combinations therapy in one dosage unit form. See ¶¶ 0189.
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 Green and Brogdon and use the BCMA CARs constructs and T-cells expressing said CARs and CAR-T of Brogdon in the kits of Green because Green teaches kits with BCMA CAR T cells and a g-secretase inhibitor and Brogdon teaches that the BCMA CARs constructs of the invention are active and effective at killing multiple myeloma cells in vitro and in vivo. Thus one would have been motivated to use the BCMA CAR T-cells of Brogdon in the kits of Green given the effectiveness of the Brogdon BCMA CAR T-cells.
8. Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/090364 (Green et al. May 09, 2019), “Green” as applied to claims 37, 38, 47, 49-53 and 55-64 above, and further in view of US 2009/0220524 A1 (Iwatsubo et al. Sep. 3, 2009), “Iwatsubo”.
Green teaches as set forth above, but does not teach that the g-secretase inhibitor is a nicastrin specific binding protein.
Iwatsubo teaches anti-nicastrin antibodies which inhibit g-secretase activity for the treatment of Alzheimer’s disease and cancer. See Abstract and ¶¶ 0001 and 0015-0019.
Iwatsubo teaches the anti-nicastrin antibodies PPMX0408 or PPMX0410 that inhibit g-secretase activity. See Examples 11 and 15 and Figs. 11 and 22A-C,
Iwatsubo teaches the anti-nicastrin antibodies inhibited the proliferation and viability of cancer and leukemia cell lines. See Examples 12 and 13 and Figs. 15 and 18.
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 Green and Iwatsubo and use the g-secretase inhibiting anti-nicastrin antibodies of Iwatsubo in the kits of Green because Green teaches kits with BCMA CAR T cells and a g-secretase inhibitor and Iwatsubo teaches anti-nicastrin antibodies which inhibit g-secretase activity for the treatment of cancer. Thus one would have been motivated to use the g-secretase inhibiting anti-nicastrin antibodies of Iwatsubo in the kits of Green given the effectiveness of the g-secretase inhibiting anti-nicastrin antibodies of Iwatsubo.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 37, 38, 47, 49-53 and 55-64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,193,994 B2 (Green et al. in view of WO 2019/090364 (Green et al. May 09, 2019), “Green”.
The ‘994 claims are drawn to:
1. A method of treatment, the method comprising: (a) administering a T cell therapy to a subject having multiple myeloma, the cell therapy comprising a dose of T cells expressing a recombinant receptor, wherein the recombinant receptor specifically binds to BCMA; and (b) administering to the subject a compound of the structure:
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or a stereoisomer thereof, or a pharmaceutically acceptable salt or hydrate of either of the foregoing.
6. The method of claim 1, wherein the recombinant receptor is a chimeric antigen receptor.
21. The method of claim 1, wherein the antigen-binding domain is an scFv comprising an amino acid sequence having at least at or about 90% sequence identity to SEQ ID NO:188.
22. The method of claim 21, wherein the antigen-binding domain is an scFv comprising the amino acid sequence set forth in SEQ ID NO:188.
24. The method of claim 1, wherein the method further comprises administering a lymphodepleting chemotherapy prior to administration of the T cell therapy and/or wherein the subject has received a lymphodepleting chemotherapy prior to administration of the dose of T cells expressing a recombinant receptor.
25. The method of claim 24, wherein the lymphodepleting chemotherapy comprises administering fludarabine and/or cyclophosphamide to the subject.
Compound 1 is g-secretase inhibitor. See column 9-lines 1-20.
The ‘994 claims teach as set forth above, but do not teach a kit for treating multiple myeloma, comprising (a) a unit dosage of a T cell expressing a chimeric antigen receptor (CAR), wherein the CAR comprises a hydrophobic portion disposed between an extracellular component and an intracellular component, wherein the extracellular component comprises a BCMA-specific binding domain, and (b) a unit dosage of a γ-secretase inhibitor.
Green teaches as set forth above.
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 the ‘994 claims and Green and add the anti-BCMA CAR T cells and the γ-secretase inhibitor of compound 1 and chemotherapeutic agents or IL-2 to the kits of Green in unit dosage form because the ‘994 claims teach treatment of multiple myeloma with the anti-BCMA CAR T cells and the γ-secretase inhibitor of compound 1 and Green teaches placing these therapeutic agents in kits in unit dose form . One would have been motivated to put the therapeutic agents the ‘994 claims and Green in a kit for convenience, consistency, and/or for the purpose of commercial sale.
10. Claim 48 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,193,994 B2 (Green et al. in view of WO 2019/090364 (Green et al. May 09, 2019), “Green” as applied to claims 37, 38, 47, 49-53 and 55-64 above and further in view of US 2016/0046724 A1 (Brogdon et al. Feb. 18, 2016, IDS), “Brogdon”.
The ’994 claims and Green teach as set forth above, but do not teach that the BCMA CAR comprises a scFv from the C11D5.3, C12A3.2, or C13F12.1 antibody
Brogdon teaches as set forth above.
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 the ’994 claims, Green and Brogdon and use the BCMA CARs constructs and T-cells expressing said CARs and CAR-T of Brogdon in the kits of the ’994 claims and Green because Green teaches kits with BCMA CAR T cells and a g-secretase inhibitor and Brogdon teaches that the BCMA CARs constructs of the invention are active and effective at killing multiple myeloma cells in vitro and in vivo. Thus one would have been motivated to use the BCMA CAR T-cells of Brogdon in the kits of the ’994 claims and Green given the effectiveness of the Brogdon BCMA CAR T-cells.
11. Claim 48 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,193,994 B2 (Green et al. in view of WO 2019/090364 (Green et al. May 09, 2019), “Green” as applied to claims 37, 38, 47, 49-53 and 55-64 above and further in view of US 2009/0220524 A1 (Iwatsubo et al. Sep. 3, 2009), “Iwatsubo”.
The ’994 claims and Green teach as set forth above, but do not teach the g-secretase inhibitor is a nicastrin specific binding protein.
Iwatsubo teaches as set forth above.
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 the ’994 claims, Green and Iwatsubo and use the g-secretase inhibiting anti-nicastrin antibodies of Iwatsubo in the kits of the ’994 claims and Green because Green teaches kits with BCMA CAR T cells and a g-secretase inhibitor and Iwatsubo teaches anti-nicastrin antibodies which inhibit g-secretase activity for the treatment of Alzheimer’s disease and cancer. Thus one would have been motivated to use the g-secretase inhibiting anti-nicastrin antibodies of Iwatsubo in the kits of the ’994 claims and Green given the effectiveness of the g-secretase inhibiting anti-nicastrin antibodies of Iwatsubo.
Conclusion
12. 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