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 .
DETAILED ACTION
Claim Status
Applicant’s amendment filed June 10, 2024 has been received and entered.
Claims 4, 8, 10, 15, 22, 26, 28, 33 have been amended.
Claims 5-7, 9, 11-12, 16, 23-25, 27, 29-30, and 34 have been canceled.
Claims 1-4, 8, 10, 13-15, 17-22, 26, 28, and 31-33 are pending and under consideration.
Priority
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, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US22/20459 filed March 15, 2022, which is a continuation of U.S. Application 17/209,160 filed March 22, 2021, which is a continuation-in-part of PCT/US19/59275 filed October 31, 2019, which claims the benefit of U.S. Provisional Application 62/753,485 filed October 31, 2018.
However, Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date 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 35 U.S.C. 112(a) except for the best mode requirement. 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 35 U.S.C. 112(a) for one or more claims of this application.
The instant claims are drawn to a method for treating or preventing CAR T cell related toxicity in a subject in need thereof, the method comprising administering to the subject CAR T cells having a GM-CSF gene inactivation, GM-CSF gene knock-down or gene knockout, wherein after administration the CAR T cells expand and persist in blood of the subject leading to improved OSS, PFS, and OS compared to WT CAR T cells and complete or partial remission of the cancer and/or tumor.
The administration of GM-CSFk/o CAR T cells for preventing CAR T cell toxicity as recited in instant claims 1-4, 8, 17, 19-22, 26 was first disclosed in provisional application 62/753,485 filed October 31, 2018.
However, prior applications 62/753,485 and PCT/US19/59275, do not disclose or contemplate the expansion or persistence of GM-CSFk/o CAR T cells as set forth in instant claims 10, 18, and 28. The first disclosure of expansion and persistence of GM-CSFk/o CAR T cells is in application 17/209,160. In addition, improved tumor efficacy as recited in claims 14-15 is first disclosed in PCT/US19/59275. However, there is no mention of area under the curve (AUC) as recited in claim 13 in any of the prior applications or the instant specification.
Therefore, the claims are entitled to the benefit of the following priority dates as follows:
62/753,485 filed October 31, 2018 – Claims 1-4, 8, 17, 19-22, and 26
PCT/US19/59275 filed October 31, 2019 – Claims 14-15
17/209,160 filed March 22, 2021 – Claims 10, 18, and 28
18/283196 filed September 20, 2023 – Claim 13
Should Applicant disagree with the examiner’s factual determination as to the disclosure of the particular subject matter, Applicant may point out the particular places within the prior applications that disclose the aforementioned limitations.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on September 20, 2023 and August 18, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Interpretation
Claim 15 recites “the method of claim 12”, however, claim 12 has been canceled. For the purpose of examination, claim 15 is being treated as “the method of claim 10”.
Claim 17 is drawn to a method for increasing CAR T cell proliferation by administering GM-CSFk/o CAR T cells. The CAR T cell proliferation is interpreted as referring to increasing proliferation of GM-CSFk/o CAR T cells versus WT CAR T cells, and is not interpreted as administering GM-CSFk/o CAR T cells after WT CAR T cell therapy (e.g., CART19), which is not supported by the instant disclosure.
Claim 33 recites “the method of claim 30”, however, claim 30 has been canceled. For the purpose of examination, claim 33 is being treated as “the method of claim 28”.
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.
Claims 10, 13-15, 18-20, 28, and 31-33 are rejected under 35 U.S.C. 112(b) second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 10 and 28 recite, “the GM-CSFk/o CAR T cells expand and persist in blood of the subject from a peak level of GM-CSFk/o CAR T cell expansion during the first 30 days after administration of the GM-CSFk/o CAR T cells and expansion of the GM-CSFk/o CAR T cells up to at least 90 days to 180 days after the administration”. The claims further recite that “expansion and persistence can continue for up to 24 months”.
It is unclear how the GM-CSFk/o CAR T cells can peak at 30 days if they continue to expand 90-180 days, continuing up to 24 months”. Specifically, how can the number of CAR T cells be greater at day 30 than at days 90-180, or even at 2 years, if they continue to expand and persist? Furthermore, the instant specification provides no definition for “peak level” or means of measuring a “peak level” of GM-CSFk/o CAR T cells.
In addition, claims 10 and 28 recite that the expansion of GM-CSFk/o CAR T cells up to at least 90 days to 180 days. It is unclear whether the cells expand and persist for up to 90 days, or do they expand for at least 90 days? For example, if the cells expand and persist for 50 days, which is “up to” 90 days, but is not “at least 90 days”, is that within the scope of the claim? As such, one of ordinary skill in the art cannot determine the metes and bounds of the claims.
Claims 13-15 and 31-33 are included in the rejection as they depend from a rejected independent claim and do not clarify the issue.
Claims 13 and 31 recite, “persistence as measured by area under the curve”, however it is unclear what the curve in which persistence is being compared to.
Claims 14-15 and 32-33 are included in the rejection as they depend from a rejected independent claim and do not clarify the issue.
Claim 15 recites the limitation "the method of claim 12". However, claim 12 has been canceled and there is insufficient antecedent basis for this limitation in the claim.
Claim 18 recites the limitation "expansion of GM-CSFk/o CAR-T cells". However, there is insufficient antecedent basis for this limitation in the claim.
Claim 19 recites “wherein reduction or elimination of the production of GM-CSF by the GM-CSFk/o CAR-T cells increases production and expansion of the GM-CSF by the GM-CSFk/o CAR-T cells”. The claim language as written is confusing. Specifically, how can reducing or eliminating GM-CSF production in GM-CSFk/o CAR-T cells increase the production of GM-CSF in the same cells?
Claim 20 is included in the rejection because it depends from a rejected independent claim and do not clarify the issue.
Claim 33 recites the limitation "the method of claim 30". However, claim 30 has been canceled and there is insufficient antecedent basis for this limitation in the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1 is rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Sentman et al. (WO 2015/066262; cited IDS 8/18/2025) (“Sentman”). This reference qualifies as prior art under both 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
The instant claims are drawn to a method for treating or preventing CAR T cell related toxicity in a subject comprising administering CAR T cells having a GM-CSF gene inactivation, GM-CSF gene knock-down or gene knockout (GM-CSFk/o CAR T cells)
Sentman discloses a method for preventing toxicity of adoptive cell therapy comprising administering to a subject in need, a population of cells deficient in the expression or activity of GM-CSF thereby preventing toxicity of the adoptive cell therapy [claim 1], wherein the adoptive cell therapy comprises chimeric antigen receptor-bearing lymphocyte therapy [claim 3], wherein the population of cells comprise a GM-CSF gene deletion or GM-CSF gene disruption [claim 4].
Therefore, absent a showing of any difference, the methods disclosed by the prior art are deemed to anticipate the claimed methods.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Sentman et al. (WO 2015/066262; cited IDS 8/18/2025) (“Sentman”).
The instant claims are drawn to a method for treating or preventing CAR T cell related toxicity in a subject comprising administering CAR T cells having a GM-CSF gene inactivation, GM-CSF gene knock-down or gene knockout (GM-CSFk/o CAR T cells), wherein the subject has lymphoma or leukemia, such as lymphoblastic leukemia (ALL), wherein the GM-CSFk/o CAR T cells target CD19.
The teachings of Sentman have been set forth above.
Sentman discloses methods for preventing toxicity of CAR T cell therapy by administering to a subject in need, GM-CSF CAR T cells as the result a GM-CSF gene deletion or GM-CSF gene disruption. Such toxicity includes a cytokine storm or cytotoxicity toward healthy cells [0005]. Cells deficient in GM-CSF can result in a measurable decrease in cytokine production up to 90% [0012].
The CAR-modified T cells can be engineered to recognize tumor cells via binding of the CAR to its tumor-associated antigen, independent of T cell receptor-MHC/peptide interactions. As a result, T cells are activated and can efficiently eliminate tumor cells. Antigens specific for cancer which may be targeted by the CARs include CD19 for B cell lymphoma [0062] and additional targets of B cell diseases [0063]. The CAR T cells can be used to treat a variety of cancers including acute lymphoblastic leukemia, B cell lymphoma and various leukemias [0072]. Such therapy can reduce the size of a tumor, eliminate tumor growth or regrowth [0069]. Using GM-CSF deficient CAR T cells can prevent a cytokine storm that may occur when a high dose of activated lymphocytes or CAR-bearing lymphocytes are given to a patient [0011].
Sentman discloses GM-CSF deficient CAR T cells for the use in treating various cancers as recited in the instant claims. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Sentman et al. (WO 2015/066262; cited IDS 8/18/2025) (“Sentman”) as applied to claims 1, 3-4, and 8 above, and further in view of Garfall et al. (US 2018/0252727; cited IDS 8/18/2025) (“Garfall”).
The instant claims are drawn to a method for treating or preventing CAR T cell related toxicity in a subject comprising administering CAR T cells having a GM-CSF gene inactivation, GM-CSF gene knock-down or gene knockout (GM-CSFk/o CAR T cells), wherein the CAR T cell related toxicity comprises neurotoxicity and/or cytokine release syndrome (CRS).
The teachings of Sentman are set forth above.
Sentman teaches the GM-CSFk/o CAR T cells can be used to cytokine storm, but does not specifically teach the GM-CSFk/o CAR T cells are used to treat CRS or neurotoxicity.
Garfall teaches CAR T cells with anti-CD19 specificity can be used to treat hematologic malignancies associated with CD19 expression, such as diffuse large B cell lymphoma and multiple myeloma, but the treatment is associated with adverse advents, including cytokine release syndrome (CRS). CRS is a serious and common adverse side effect CAR T cell-based therapies, with potentially life-threatening toxicity [0005, 0156]. Symptoms of CRS can include neurologic toxicity, disseminated intravascular coagulation, and cardiac dysfunction [0326].
Garfall teaches that GM-CSF is elevated in patients with the most severe form of CRS (grades 4-5) [0238, 0850], which makes it an ideal target for alleviating CRS.
The teachings of Sentman differ from the instant invention in that although GM-CSF deficient CAR T cells are disclosed to prevent cytokine storm associated with CD19 CAR T therapy in treating various cancers, the subjects are not explicitly taught as having CRS.
It would have been obvious to one of ordinary skill in the art to prevent or minimize CRS by administering GM-CSF deficient CAR T cells given that Sentman teaches administering GM-CSF deficient CAR T cells to prevent cytokine storm and Garfall teaches GM-CSF is implicated in severe CRS associated with CAR T therapy. Thus, the prior art references as combined provided a prima facie case of obviousness for the instant invention.
Claims 1, 3, 10, 13-15, 17-22, 26, 28, and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Sentman et al. (WO 2015/066262; cited IDS 8/18/2025) (“Sentman”) as applied to claims 1, 3-4, and 8 above, and further in view of Durrant et al. (US 2019/0284271) (“Durrant”).
The instant claims are drawn to a method for treating or preventing CAR T cell related toxicity in a subject comprising administering CAR T cells having a GM-CSF gene inactivation, GM-CSF gene knock-down or gene knockout (GM-CSFk/o CAR T cells), wherein GM-CSF production is reduced up to 99%, in a patient with cancer and/or a tumor, wherein the levels of the GM-CSFk/o CAR T cells expand and persist in the blood of the subject, peaking at 30 days, with continued expansion at least 90 to 180 days post administration, further expanding and persisting in the blood up to 24 months to achieve an anti-cancer or anti-tumor efficacy that is complete or partial remission. The peak expansion is enhanced relative to wild type CAR T cells and persistence as measured by CAR AUC is improved compared to WT CAR T cells, resulting in improved objective response rates (ORR), improved progression free survival (PFS), or improved overall survival (OS) compared to WT CAR T cells.
The teachings of Sentman are set forth above.
Sentman teaches administering GM-CSF deficient CAR T cells for the treatment cancer, but does not disclose any information regarding the expansion and/or persistence of the CAR T cells.
Durrant teaches CAR T cell therapy is currently limited by the risk of life-threatening neurotoxicity and cytokine release syndrome, and despite active management, all CAR T responders experience some degree of CRS, with up to 50% of patients treated with CD19 CAR T developing at least grade 3 CRS or neurotoxicity. GM-CSF levels and T-cell expansion are the factors most associated with grade 3 or higher CRS and neurotoxicity [0086].
Durrant teaches methods for reducing or preventing immunotherapy related toxicity comprising administering CAR T cells with a GM-CSF gene knockout (GM-CSFk/o CAR T cells) [Abstract]. Durrant teaches that blocking GM-CSF can increase the efficacy of CAR T immunotherapy by increasing CAR T cell expansion [0021] which inhibits or reduces the incidence or the severity of CAR T related toxicity, such as neurotoxicity, CRS, or a combination thereof [0023]. The inhibition of CRS thereby leads to an increase in survival time and/or time to relapse in treated subjects [0024].
Durrant disrupted GM-CSF through CRISPR/Cas9 gene editing during the process of CAR T cell manufacturing, resulting in functional CAR T cells that produce significantly less GM-CSF upon activation, but continue to produce normal effector functions, resulting in enhanced disease control compared to CART19 cells [0377].
Figure 23A illustrates increased ex vivo expansion of GM-CSFk/o CAR T cells compared to control CAR T cells [0052]. Durrant further teaches that CAR T expansion is associated with improved overall response rate, as illustrated in the CAR AUC (area under the curve), defined as cumulative levels of CAR +cells/µL of blood over the first 28 days post CAR T administration [0049, Fig. 21]. Figure 26I illustrates complete tumor elimination after treatment with GM-CSFk/o CAR T cells. Figure 29C illustrates GM-CSFk/o CAR T cells enhances overall survival compared to wild type CART19 in a high tumor burden relapse xenograft model of ALL. In all, these results strongly suggest that modulating myeloid cell behavior through GM-CSF blockade helps control CAR T cell mediated toxicities and reduce their immunosuppressive features to improve leukemic control. This approach can be used to abrogate neurotoxicities and CRS through GM-CSF neutralization that also enhances CAR-T cell functions [0407].
The teachings of Durrant differ from the instant claimed invention in that even though GM-CSFk/o CAR T cells demonstrate a significant increase in proliferation of CAR T cells, the peak expansion at 30 days and persistence of the GM-CSFk/o CAR T cells for 90 days to 24 months is not explicitly taught. However, Figure 29C (below) shows that in the GM-CSFk/o CAR T treatment group, the percent survival drops from 100% to 50% around day 30 (i.e., peak level) with levels of 25% survival maintained until the study ended at day 50 (i.e., persistence). There is no data provided after day 50, so it is unclear whether the levels of GM-CSFk/o CAR T would continue to persist up to 24 months as recited in the instant claims.
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MPEP § 2112 provides guidance as to the Examiner's burden of proof for a rejection of claims under 35 U.S.C. 102 or 103 based upon the express, implicit, and inherent disclosures of a prior art reference. The case law clearly states that something which is old does not become patentable upon the discovery of a new property. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art' s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
Thus, the claiming of a new use, new function or unknown property that is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Further, the court has held that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999).
The case law specifically applies to the instant application where Applicant has claimed a composition in terms of a function, property or characteristic of immune stimulation and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference. The examiner's assertion of inherency is based upon the structural similarity between the composition of the prior art and the claimed composition.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established and the burden of proof rests upon the Applicant to demonstrate that the prior art does not necessarily or inherently possess the characteristics of Applicant' s claimed product. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977)). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Accordingly, it would be obvious to one having ordinary skill in the art at the time of invention, to utilize the GM-CSF deficient CAR T cells as taught by Sentman to treat cancers such as ALL, that prevent CRS and neurotoxicity associated with CAR T cell therapy along with increased proliferation that leads to significantly reduced CRS and greater overall survival as evidenced by Durrant. Thus, the prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Nonstatutory Double Patenting
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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.
Claims 1-4 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17/209,160.
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the same GM-CSFk/o CAR T cells for treating CAR T cell related toxicity associated with CAR T therapies for the treatment of cancers, including lymphomas and leukemias. As such, the instant claimed invention is an obvious modification of the claims of the copending application.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 10, 13-15, 17-22, 26, 28, and 31-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17/209,160, in view of Durrant et al. (US 2019/0284271) (“Durrant”).
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the same GM-CSFk/o CAR T cells for treating CAR T cell related toxicity associated with CAR T therapies for the treatment of cancers, including lymphomas and leukemias.
The instant claims differ from the copending claims in that they do not recite administering GM-CSFk/o CAR T cells increase CAR T cell proliferation that expand and persist in blood of the subject from a peak level during the first 30 days, expanding up to at least 90 days to 180 days, and wherein persistence in the blood of the subject achieves an anti-cancer or anti-tumor efficacy from 90 days to 24 month and peak expansion is enhanced relative to wild type CAR T cells as measured by CAR area under the curve (AUC) resulting in improved objective response rates (ORR), improved progression free survival (PFS), or improved overall survival (OS), with complete or partial remission of the cancer and/or the tumor.
The teachings of Durrant have been set forth above. Specifically, Durrant teaches increased ex vivo expansion of GM-CSFk/o CAR T cells compared to control CAR T cells is associated with improved overall response rate, as illustrated in the CAR AUC. Further, treatment with GM-CSFk/o CAR T cells results in complete tumor elimination. Durrant teaches in the GM-CSFk/o CAR T treatment group, the percent survival drops from 100% to 50% around day 30 (i.e., peak level) with levels of 25% survival maintained until the study ended at day 50 (i.e., persistence).
MPEP § 2112 provides guidance as to the Examiner's burden of proof for a rejection of claims under 35 U.S.C. 102 or 103 based upon the express, implicit, and inherent disclosures of a prior art reference. The case law clearly states that something which is old does not become patentable upon the discovery of a new property. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art' s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
Thus, the claiming of a new use, new function or unknown property that is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Further, the court has held that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999).
The case law specifically applies to the instant application where Applicant has claimed a composition in terms of a function, property or characteristic of immune stimulation and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference. The examiner's assertion of inherency is based upon the structural similarity between the composition of the prior art and the claimed composition.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established and the burden of proof rests upon the Applicant to demonstrate that the prior art does not necessarily or inherently possess the characteristics of Applicant' s claimed product. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977)). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Durrant.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 15-17 of copending Application No. 17/290,185.
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the same GM-CSFk/o CAR T cells for treating CAR T cell related toxicity associated with CAR T therapies for the treatment of cancers, including lymphomas and leukemias. As such, the instant claimed invention is an obvious modification of the claims of the copending application.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 10, 13-15, 17-22, 26, 28, and 31-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 15-17 of copending Application No. 17/290,185, in view of Durrant et al. (US 2019/0284271) (“Durrant”).
Although the claims at issue are not identical, they are not patentably distinct from each other because they teach the same GM-CSFk/o CAR T cells for treating CAR T cell related toxicity associated with CAR T therapies for the treatment of cancers, including lymphomas and leukemias.
The instant claims differ from the copending claims in that they do not recite administering GM-CSFk/o CAR T cells increase CAR T cell proliferation that expand and persist in blood of the subject from a peak level during the first 30 days, expanding up to at least 90 days to 180 days, and wherein persistence in the blood of the subject achieves an anti-cancer or anti-tumor efficacy from 90 days to 24 month and peak expansion is enhanced relative to wild type CAR T cells as measured by CAR area under the curve (AUC) resulting in improved objective response rates (ORR), improved progression free survival (PFS), or improved overall survival (OS), with complete or partial remission of the cancer and/or the tumor.
The teachings of Durrant have been set forth above. Specifically, Durrant teaches increased ex vivo expansion of GM-CSFk/o CAR T cells compared to control CAR T cells is associated with improved overall response rate, as illustrated in the CAR AUC. Further, treatment with GM-CSFk/o CAR T cells results in complete tumor elimination. Durrant teaches in the GM-CSFk/o CAR T treatment group, the percent survival drops from 100% to 50% around day 30 (i.e., peak level) with levels of 25% survival maintained until the study ended at day 50 (i.e., persistence).
MPEP § 2112 provides guidance as to the Examiner's burden of proof for a rejection of claims under 35 U.S.C. 102 or 103 based upon the express, implicit, and inherent disclosures of a prior art reference. The case law clearly states that something which is old does not become patentable upon the discovery of a new property. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art' s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
Thus, the claiming of a new use, new function or unknown property that is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Further, the court has held that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999).
The case law specifically applies to the instant application where Applicant has claimed a composition in terms of a function, property or characteristic of immune stimulation and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference. The examiner's assertion of inherency is based upon the structural similarity between the composition of the prior art and the claimed composition.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established and the burden of proof rests upon the Applicant to demonstrate that the prior art does not necessarily or inherently possess the characteristics of Applicant' s claimed product. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977)). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
As such, the instant claimed invention is an obvious modification of the claims of the copending application in view of Durrant.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1644
/DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644