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 .
Priority
The instant application is a continuation of Application No. 17/180754, filed 20 February 2021 (now US Patent No. 12252701 B2). Acknowledgement is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 62/979,001 filed 20 February 2020, 63/010,240 filed 15 April 2020, 63/031,224 filed 28 May 2020, 63/044,676 filed 26 June 2020, 63/060,819 filed 04 August 2020, and 63/125,633 filed 15 December 2020.
Status of the Claims
Applicant’s preliminary submission filed 10 February 2025 has been entered. Claims 34-53 are pending. Claims 1-33 have been cancelled without prejudice or disclaimer and claims 34-53 have been newly added. Therefore, prosecution on the merits commences for claims 34-53.
Drawings
The replacement drawing sheets filed 27 May 2025 are acknowledged and entered into the application file.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because there are two sequence identifiers within Paragraph [0345] of the instant Specification filed 10 February 2025.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specification
Applicant’s amendments to the Specification filed 10 February 2025 are acknowledged and entered into the application file. However, the lengthy Specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the Specification.
The instant disclosure is objected to for referencing colors within the figures, when colored drawings have not been submitted in the application. More specifically, the Specification references colors at least within Paragraphs [0039], [0061], [0065]-[0066], [0070], [0072], [0085], and [0087]-[0088] in reference to Figures 2, 24, 28-29, 33, 35, 48, and 50-51. Applicant is requested to review the Specification to identify any additional references to colors within the drawings and delete as reference to specific colors within the text of the Specification.
Appropriate correction is required.
Claim Objections
Claims 34-35, 37-39, 42-43, 45, 50, and 52 are objected to because of the following informalities:
Regarding claim 34: The instant claim is objected to for failing to have a space between “T” and “or” in Line 5.
The instant claim is further objected to for failing to recite a comma between “administration” and “wherein” in Line 6.
The instant claim is further objected to for reciting “IL-I” instead of “IL-1” in Line 8.
Appropriate correction is required.
Regarding claim 35: The instant claim is objected to for having an extraneous space between “post-“ and “immunotherapy” in Line 2.
Appropriate correction is required.
Regarding claim 37: The instant claim is objected to for failing to have a space between “T” and “or” in Line 4.
Appropriate correction is required.
Regarding claim 38: The instant claim is objected to for reciting “CART cell” instead of “CAR T cell”, as has been otherwise utilized throughout the claim language.
Appropriate correction is required.
Regarding claim 39: The instant claim is objected to for reciting “selected from” instead of “selected from the group consisting of” in Line 1.
Appropriate correction is required.
Regarding claim 42: The instant claim is objected to for capitalizing “Grade”, as well as failing to have to a space between “of” and “NE/ICANS” in Line 5.
The instant claim is further objected to for failing to provide a comma between “T cells” and “innate T cells” in Line 10.
The instant claim is further objected to for reciting an extraneous parenthesis in Line 11.
Appropriate correction is required.
Regarding claim 43: The instant claim is objected to for reciting “selected from” instead of “selected from the group consisting of” in Line 1.
Appropriate correction is required.
Regarding claim 45: The instant claim is objected to for reciting an extraneous “or” prior to “about 50 mg to about 500 mg” in Line 4.
Appropriate correction is required.
Regarding claim 50: The instant claim is objected to for defining the acronym “CAR”, wherein the first recitation of “CAR” is in independent claim 34.
Appropriate correction is required.
Regarding claim 52: The instant claim is objected to for failing to have a space between “T” and “or” in Lines 2 and 4.
Appropriate correction is required.
Claim Interpretation
Under the broadest reasonable interpretation of each claim, all of the “optional” limitations are not 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.
Claims 34-52 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.
Regarding claim 34: The instant claim recites the limitation “immunotherapy (T or non-T cells, TCR, CAR)” in Lines 1-2 and 5. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Instant claims 35-51 are included in the rejection because they depend from instant claim 34
and fail to correct the deficiencies of the parent claim.
Appropriate correction is required.
Regarding claim 35: The instant claim recites the limitation “immunotherapy (T or non-T cells, TCR, CAR)” in Line 2. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 36: The instant claim recites the limitation “post-neurotoxicity (post-ICANS)” in Line 2. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 37: The instant claim recites the limitations “acute interval (2-4 weeks)” in Line 2 and “immunotherapy (T or non-T cells, TCR, CAR)” in Lines 3-5. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 41: The instant claim recites the limitations “filgotinib (or another JAK/STAT inhibitor)” in Line 1, “agents (tocilizumab and steroids)” in Line 2, and “immunotherapy (T or non-T cells, TCR, CAR)” in Line 3. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
It is also of note that the limitation “filgotinib (or another JAK/STAT inhibitor) further renders the scope of the claim indefinite, as it is unclear if the JAK/STAT inhibitor must be filgotinib, or if the claim more broadly covers any JAK/STAT inhibitor.
The instant claim also recites the phrase "such as" in Line 4, which renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Appropriate correction is required.
Regarding claim 42: The instant claim recites the limitations “neurologic events (NE or ICANS)” in Line 2, “immunotherapy (T or non-T cells, TCR, CAR)” in Lines 3 and 8, and “activity (cytokine production)” in Line 10. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 45: The instant claim recites the limitations “JAK/STAT inhibitor (filgotinib)” in Line 1, “from 2.5 mg to 50 mg (2.5-5 mg, 5- 10 mg, 10- 15 mg, 15-20 mg, 20-25 mg, 25-30 mg, 30-35 mg, 35-40 mg, 40-45 mg, or 45-50 mg)” in Lines 4-6, and “daily (5 mg to 100 mg total per day)” in Line 6. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 46: The instant claim recites the limitations “JAK/STAT inhibitor (filgotinib)” in Line 1, “after (at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 hours or days or 1, 2, 3, or 4 weeks prior to or after)” in Lines 2-3, “dose (a first dose, second dose)” in Line 3, and “immunotherapy (T or non-T cells, TCR, CAR)” in Lines 3-4. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 47: The instant claim recites the limitation “JAK/STAT inhibitor (filgotinib)” in Line 1. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 48: The instant claim recites the limitation "the method of claim 34, wherein filgotinib is administered…" in Line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim, as parent claim 34 does not draw to nor recite filgotinib. For purposes of prosecution, the instant claim will be interpreted as necessitating any JAK/STAT inhibitor, as is stated in claim 34.
The instant claim further recites the limitation “immunotherapy (T or non-T cells, TCR, CAR)” in Line 2. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 49: The instant claim recites the limitation “immunotherapy (T or non-T cells, TCR, CAR)” in Line 3. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
Appropriate correction is required.
Regarding claim 50: The instant claims recites the limitation "the T cell immunotherapy" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “T cell immunotherapy” within the instant claim or parent claim 34. Instead, parent claim 34 is broadly directed to immunotherapy. Therefore, the metes and bounds of the claim cannot be readily determined, thus rendering the scope of the claim indefinite.
Appropriate correction is required.
Regarding claim 51: The instant claims recites the limitation "the T cell immunotherapy" in Line 1. There is insufficient antecedent basis for this limitation in the claim, as there is no prior recitation of “T cell immunotherapy” within the instant claim or parent claims 34 or 49. Instead, parent claims 34 and 49 are broadly directed to immunotherapy. Therefore, the metes and bounds of the claim cannot be readily determined, thus rendering the scope of the claim indefinite.
Appropriate correction is required.
Regarding claim 52: The instant claim recites the limitation “immunotherapy (T or non-T cells, TCR, CAR)” in Lines 2 and 4-5. The scope of the claim is indefinite, as it is unclear if the parenthetical language is required by the claim, or is instead optional. Therefore, since the recitation of the parenthetical language is being treated as exemplary language, the metes and bounds of the claim cannot be determined.
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.
Claims 34-52 are rejected under 35 U.S.C. 102(a)(1) and 35 USC 102(a)(2) as being anticipated by Gill et al (US 2019/0336504 A1, of record on IDS filed 10 February 2025).
Gill et al disclose compositions and methods for treating or preventing cytokine release syndrome by administering a CAR therapy with a JAK-STAT kinase inhibitor (Abstract).
As such, Gill et al disclose a method of treating cytokine release syndrome following CAR therapy, wherein the method comprises administering to a subject in need thereof (i) a JAK-STAT kinase inhibitor, (ii) a CAR T cell therapy, and (iii) an IL-6 inhibitor (Paragraphs [0005], [0008]-[0009], [0014], [0016], [0018], [0062]-[0064], [0065], [0073]-[0076], [0998]-[0999]). Gill et al further disclose that the administration of the JAK-STAT kinase inhibitor ameliorates cytokine release syndrome severity or prevents cytokine release syndrome after CAR T cell therapy without impairing the anti-tumor effect of the CAR T cell therapy, and without having a direct anti-tumor activity itself (Paragraphs [0005], [0012], [0245], [0756], [0984], [1078], [1087], [1091]-[1092]). Gill et al further disclose that the administration reduces the extent of hemophagocytic lymphohistiocytosis (HLH), also termed Macrophage Activation Syndrome (MAS) following CAR T cell therapy (Paragraphs [0930], [1107]). Gill et al further disclose that the subjects are clinically monitored following administration of the CAR T cell therapy, with some subjects in the intensive care unit (Paragraphs [0142], [0200], [0711]-[0712], [1015], [1086], [1089], [1205]).
Gill et al further disclose that the JAK/STAT inhibitor is administered either prophylactically before the onset of toxicity symptoms or post-cytokine release syndrome onset (Paragraphs [0318]-[0320], [1060]). Gill et al further disclose that the JAK-STAT kinase inhibitor and CAR T cell are administered sequentially, concurrently, or within a detailed treatment interval, wherein the detailed treatment interval involves a dose of the JAK-STAT kinase inhibitor administered prior to the CAR T cell therapy and 2 weeks after the administration of the CAR T cell therapy (Paragraphs [0077]-[0115], [0251], [0281], [0311]-[0313]).
Gill et al further disclose that the JAK-STAT kinase inhibitor is administered at a dose of 2.5 mg to 50 mg twice daily, resulting in an administration of 5 mg to 100 mg total per day (Paragraph [0105]).
Gill et al disclose that the administration of the JAK-STAT kinase inhibitor with CAR T therapy decreases the serum levels of inflammatory cytokines, such as IFN-gamma, GM-CSF, and TNF-alpha (Figure 2F; Paragraph [1091]).
Gill et al further disclose that the JAK-STAT kinase inhibitor is GLPG0634, which is an alternate name for filgotinib (Paragraphs [0064], [0743], [0745], [0822]).
Gill et al further disclose that the IL-6 inhibitor is a monoclonal antibody against IL-6 or tocilizumab (Paragraphs [0016], [0066]).
Gill et al further disclose that the CAR T cells are allogeneic CAR T cells (Paragraphs [0612], [0645]-[0678]). Gill et al further disclose that the CAR T cells are anti-CD19 CAR T cells (Paragraphs [0008], [0010], [0017], [0027]-[0030], [0033], [0048]-[0052], [0059], [0089]-[0090]).
Accordingly, Gill et al anticipate the claims as follows:
Regarding claims 34 and 38: Gill et al disclose a method of ameliorating cytokine release
syndrome severity following CAR therapy, wherein the method comprises administering to a subject in need thereof (i) a JAK-STAT kinase inhibitor, (ii) a CAR T cell therapy (claim 38), and (iii) an IL-6 inhibitor, wherein the IL-6 inhibitor is a monoclonal antibody against IL-6. As the IL-6 inhibitor will inherently be administered prior to, during, or after the CAR T cell therapy, and the method of ameliorating cytokine release syndrome severity involves reducing the toxicity of the CAR T cell therapy, this therefore reads on the method of instant claim 34.
Regarding claims 35 and 47: Following the discussion of claim 34, Gill et al further disclose that the JAK/STAT inhibitor is administered prophylactically (claim 47) before the onset of toxicity symptoms. This therefore reads on the method of instant claim 35.
Regarding claim 36: Following the discussion of claim 34, Gill et al further disclose that the JAK/STAT inhibitor is administered post-cytokine release syndrome onset. This therefore reads on the method of the instant claim.
Regarding claims 37 and 46: Following the discussion of claim 34, Gill et al further disclose that the JAK-STAT kinase inhibitor and CAR T cell are administered within a detailed treatment interval, wherein a dose of the JAK-STAT kinase inhibitor is administered prior to the CAR T cell therapy and 2 weeks after the administration of the CAR T cell therapy (claim 46). This therefore reads on the method of instant claim 37.
Regarding claims 39-40: Following the discussion of claim 34, Gill et al further disclose that the JAK-STAT kinase inhibitor is GLPG0634, which is an alternate name for filgotinib (claim 40). This therefore reads on the method of instant claim 39.
Regarding claim 41: Following the discussion of claim 40, Gill et al further disclose that the JAK-STAT inhibitor – or filgotinib – is administered in combination with the IL-6 inhibitor, which includes tocilizumab. This therefore reads on the method of the instant claim.
Regarding claims 42-43: Following the discussion of claim 34, Gill et al further disclose that the administration of the JAK-STAT kinase inhibitor with CAR T therapy decreases the serum levels of inflammatory cytokines, such as IFN-gamma, GM-CSF, and TNF-alpha (claim 43). This therefore reads on method step (ii) of instant claim 42.
Regarding claim 44: Following the discussion of claim 42, Gill et al further disclose that the administration of the JAK-STAT kinase inhibitor does not interfere with the anti-tumor activity of the CAR T cell therapy. This therefore reads on the method of the instant claim.
Regarding claim 45: Following the discussion of claim 34, Gill et al further disclose that the JAK-STAT kinase inhibitor is administered at a dose of 2.5 mg to 50 mg twice daily. This therefore reads on the method of the instant claim.
Regarding claim 48: Following the discussion of claim 34, Gill et al further disclose that the administration of the JAK-STAT kinase inhibitor prevents cytokine release syndrome after CAR T cell therapy without impairing the anti-tumor effect of the CAR T cell therapy, and without having a direct anti-tumor activity itself. As this ultimately improves the therapeutic efficacy of the CAR T cell therapy, this therefore reads on the method of the instant claim.
Regarding claim 49: Following the discussion of claim 34, Gill et al further disclose that the administration of the JAK-STAT kinase inhibitor reduces the extent of hemophagocytic lymphohistiocytosis (HLH), also termed Macrophage Activation Syndrome (MAS) following CAR T cell therapy. This therefore reads on the method of the instant claim.
Regarding claim 50: Following the discussion of claim 34, Gill et al further disclose that the CAR T cells are allogeneic CAR T cells. This therefore reads on the method of the instant claim.
Regarding claim 51: Following the discussion of claim 49, Gill et al further disclose that the CARs comprised with the T cells are anti-CD19 CARs, and that the administration of the JAK-STAT kinase inhibitor does not interfere with the anti-tumor effect of the CAR T cell therapy.
Regarding claim 52: Gill et al disclose a method that comprises administering to a subject in need thereof (i) a JAK-STAT kinase inhibitor, (ii) a CAR T cell therapy, and (iii) an IL-6 inhibitor. Gill et al further disclose that the JAK-STAT kinase inhibitor and CAR T cell are administered sequentially, concurrently, or within a detailed treatment interval, wherein the detailed treatment interval involves a dose of the JAK-STAT kinase inhibitor administered (i) prior to the CAR T cell therapy and (ii) 2 weeks after the administration of the CAR T cell therapy.
Gill et al further disclose that the administration of the JAK-STAT kinase inhibitor ameliorates cytokine release syndrome severity or prevents cytokine release syndrome after CAR T cell therapy.
Gill et al further disclose that the subjects – which can initially be in the intensive care unit – are clinically monitored following administration of the CAR T cell therapy.
This therefore reads on the method of the instant claim, as the likelihood of clinically monitoring subjects in the intensive care unit – or in-patient care – would decrease with the administration of the JAK-STAT kinase inhibitor following administration of the CAR T cell therapy, as the JAK-STAT kinase inhibitor prevents cytokine release syndrome after CAR T cell therapy.
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.
Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over Gill et al (US 2019/0336504 A1, of record on IDS filed 10 February 2025).
Gill et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 53: Gill et al disclose compositions and methods for treating or preventing cytokine release syndrome by administering a CAR therapy with a JAK-STAT kinase inhibitor (Abstract).
As such, Gill et al disclose a method of manufacturing CAR T cells, wherein a population of T cells is contacted with the JAK-STAT kinase inhibitor and then transduced with the CAR (Paragraphs [0741]-[0746], [0759]).
Gill et al do not disclose that the CAR T cells pre-contacted with the JAK-STAT kinase inhibitor reduces or suppresses toxicity-associated T cell activity post-administration, as required by instant claim 53.
Gill et al do disclose, however, that the administration of the JAK-STAT kinase inhibitor to a subject ameliorates cytokine release syndrome severity or prevents cytokine release syndrome after CAR T cell therapy without impacting the activity or effect of the CAR T cells (Paragraphs [0005], [0012], [0245], [0756], [0984], [1078], [1087], [1091]-[1092]).
Therefore, it would have been prima facie obvious to have modified the method of Gill et al such that the CAR T cells pre-contacted with the JAK-STAT kinase inhibitor exhibit a reduced or suppressed toxicity-associated T cell activity post-administration. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to reduce the toxicity associated with the administration and activity of CAR T cells, and would have had a reasonable expectation of success given that Gill et al teach the in vitro contacting of the CAR T cells with the JAK-STAT kinase inhibitor and that JAK-STAT kinase inhibitors are sufficient at reducing the severity – or toxicity – of cytokine release syndrome within embodiments of the invention. See MPEP § 2143(I)(G).
Consequently, Gill et al render obvious a method of manufacturing CAR T cells, wherein a population of T cells is contacted with a JAK-STAT kinase inhibitor and then transduced with the CAR, and wherein the contacting of the CAR T cells with the JAK-STAT kinase inhibitor reduces or suppresses toxicity-associated T cell activity post-administration. This therefore renders obvious the method of the instant claim.
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.
Claims 34-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12252701 B2. It is of note that the instant claim is a CONTINUATION of U.S. Patent No. 12252701 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims render obvious the instant claims. More specifically, the patent claims are not identical because no single patent claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patented claims. The fact that each of the elements were claimed in the patent, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a method of increasing the efficacy or reducing the toxicity of immunotherapy, bi-specific T-cell engagers (BiTEs), or immune checkpoint blockade treatment in a subject in need thereof, comprising:
(i) administering to the subject a JAK/STAT inhibitor and decreasing the subject's systemic inflammatory state; or
(ii) administering to the subject a JAK/STAT inhibitor and reducing the activity of myeloid cells, MCP-1, IL-6, or activated T cells in the subject,
prior to, during, or after immunotherapy, BiTEs, or immune checkpoint blockade treatment, or T cell immunotherapy, wherein the JAK/STAT inhibitor is filgotinib metabolite GS-829845 and is administered to the subject in need thereof at a dose of about 200 mg one or more times, optionally daily, and
(iii) further comprising administering to the subject a monoclonal antibody against monocyte chemoattractant protein-1 (MCP-1).
Patent claim 2 further defines the method of patent claim 1, wherein reducing myeloid cell activity, or IL-6 activity further comprises administering to the subject a monoclonal antibody against IL-6, IL-1, CSF1R, GM-CSF or a small molecule.
This therefore renders obvious the method of instant claims 34, 39-40, and 45.
With that, instant claims 35-38, 41-44, and 46-51 are known from the patent can be further incorporated into the method rendered obvious by patent claims 1-2:
Patent claims 3-14 teach the limitations recited in instant claims 35-38, 41-44, and 46-51.
Conclusion
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/ALYSSA G WESTON/Examiner, Art Unit 1633
