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 .
Claim Status
Receipt is acknowledged of the Response to Restriction and Claim Amendments filed on 20 August, 2025. Applicant has elected the species of “modified lymphocytes and/or tumor infiltrating lymphocytes further comprising a recombinant hyaluronidase” without traverse.
Claims 69-70, and 86 are amended. No claims are added and no claims are cancelled.
Therefore, claims 69-88 are pending and under examination in the present Official Action. Claims 69 and 87 are independent claims.
Priority
The present application is (1) a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2020/049259, filed 31 August, 2020, which claims priority to United States Provisional Application Nos. 62/985,741, 62/943,207, 62/894,926, 62/894,852, 62/894,853, and 62/894,849 filed 05 March, 2020, 03 December, 2019, 02 September, 2019, 01 September, 2019, 01 September, 2019, and 01 September, 2019 respectively, and (2) a continuation-in-part of International Application No. PCT/US2019/049259 filed 02 September, 2019. Acknowledgement is made of Applicant’s claim for priority.
Therefore, the earliest possible priority for the instant application is 01 September, 2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 20 August, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 28 February, 2022 are accepted by the Examiner.
Claim Objections
Claim 83 is objected to because of the following informalities: it lacks a definite article (e.g. “the”) before “cell formulation”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 69-87 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 69 recites “and/or” in the second line of the claim. It is unclear if Applicants intend the scope of claim 69 to encompass modified lymphocytes and tumor infiltrating lymphocytes or if Applicant instead intends the scope to encompass these cell types in the alternative. Thus, the scope of claim 69 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. Claims 70-86 are further rejected for their dependency on a rejected base claim.
Claim 75 recites “and/or” in the sixth and seventh lines of the claim. It is unclear whether Applicant intends the scope of claim 75 to encompass a promoter that is active in T cells and NK cells or whether Applicant instead intends the scope of claim 75 to be directed to a promoter active either of these cell types in the alternative. It is further unclear whether Applicant intends the scope of claim 75 to encompass a polypeptide and an inhibitory RNA or whether Applicant intends the scope to encompass either of these in the alternative. Thus, the scope of claim 75 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. Claims 76-80 are further rejected for their dependency on a rejected base claim.
Claim 79 recites “and/or” in the third line of the claim. It is unclear whether Applicant intends the scope of claim 79 to encompass a cell formulation having both of the recited cell characteristics or either of them in the alternative. Thus, the scope of claim 79 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 81 recites “and/or” in the second and third lines of the claim. It is unclear whether Applicant intends the scope of claim 81 to encompass both of the cell types recited or either of them in the alternative, nor whether Applicant intends the scope of claim 81 to encompass aggregates comprising both of the recited cell types or either of them in the alternative. Thus, the scope of claim 81 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 82 recites “and/or” in the second and third lines of the claim. It is unclear whether Applicant intends the scope of claim 82 to encompass both of the cell types recited or either of them in the alternative, nor whether Applicant intends the scope of claim 82 to encompass cell formulations comprising both of the recited cell types or either of them in the alternative. Thus, the scope of claim 82 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 87 recites “and/or” six times throughout the claim in reference to T cells and/or NK cells in every recitation. It is unclear whether Applicant intends the scope of claim 87 to encompass both of the cell types recited or either of them in the alternative. Thus, the scope of claim 87 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 73 requires cell formulation of claim 70 comprises T cells. However, claim 69 requires modified lymphocytes which are modified T cells, B cells, NK cells and others. Thus it is unclear whether the genetically modified T cells of claim 73 are included in the modified lymphocytes of claim 69 or they are further added to the cell formulation.
Claim 74 recites “wherein the modified lymphocytes are derived from a peripheral blood sample”. It is unclear how modified lymphocytes are “derived from” such a sample. Said cells may be isolated from a peripheral blood sample. However, as written, claim 74 encompasses an unclear claim scope insofar as it does not state with any particularity how modified lymphocytes are to be derived from peripheral blood to fall within the scope of the claim, and there is not a definition of “derived from” in the instant specification. Thus, claim 74 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. Amending the claim to recite “wherein the modified lymphocytes are isolated from a peripheral blood sample” would obviate the rejection.
Claim 75 is indefinite in its recitation of “the modified lymphocytes are associated with a replication incompetent recombinant retroviral particle” as it is unclear as to the association or associations that are intended as being encompassed by the noted phrase. Modified lymphocytes are known in the prior art to have numerous associations, both specific and general. For example, lymphocytes can be transfected with a replication incompetent recombinant retroviral encoding a gene of interest. It is suggested that applicant clarify the intended meaning of the noted phrase. Claims 76-80 are further rejected for their dependency on a rejected base claim.
Claim 84 recites the limitation "the cells". There is insufficient antecedent basis for this limitation in the claim. Neither claim 84, nor claim 69 from which it depends recites “a plurality of cells”. Instead, claim 69 recites “modified lymphocytes and/or tumor infiltrating lymphocytes”. It is unclear whether “the cells” in claim 84 is referring to “modified lymphocytes”, “tumor infiltrating lymphocytes”, or a grouping of cells comprising both of these cell types. Thus, claim 84 is unclear and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claim 88 recites “further comprises collecting a peripheral blood sample” in the first and second lines of the claim. Claim 88 depends from claim 87 which recites a step of contacting T cells and/or NK cells with a retroviral particle, a step of collecting the modified T cells and/or NK cells, and a step of administering the T cells and/or NK cells. The scope of claim 88 is unclear insofar as it is unclear how peripheral blood is to be collected, from where, and when in the method. As written, peripheral blood can be collected at any point in the method of claim 87 so long as it is before the second step since claim 88 requires at least 10% of the monocytes present in the blood to be present in the cell formulation produced in the second step. If the collecting of peripheral blood is intended to be distinct and independent step occurring before the first and second steps of claim 87, it is unclear how the cell formulation of the second step of claim 87 can comprise any element of the peripheral blood as required by claim 88. Thus, the scope of claim 88 is unclear as written and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
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 69-88 are rejected under 35 U.S.C. 103 as being unpatentable over WO2018/009923 (Published: 11 January, 2018) (hereinafter “Frost”) (Of Record) in view of US2010/0143457 (Published: 10 June, 2010) (hereinafter “Wei”), WO2019/165097 (Published: 29 August, 2019) (hereinafter “Ang”) (Of Record), WO2017/177149 (Published: 12 October, 2017) (hereinafter “Low”), Li et al. Autoimmunity 52.3 (2019): 102-107. (published: 25 June, 2019) (hereinafter “Li”) (Of Record), and Kleiveland et al. Peripheral Blood Mononuclear Cells. The Impact of Food Bioactives on Health: in vitro and ex vivo models [Internet]. Cham (CH): Springer; 2015. Chapter 15. (hereinafter “Klieveland”).
Regarding claim 69, Frost discloses methods for genetically modifying T cells and/or NK cells (lymphocytes) with replication incompetent recombinant retroviruses, T cell and/or NK cell products of these methods, and methods of using such cells as an adoptive cell therapy (Frost, Abstract). Frost teaches modifying T cells to produce CAR T cells and their use for treating tumors (Frost, Abstract, [0005], [0429]).
Frost does not teach recombinant hyaluronidase or formulating the cells for subcutaneous administration (intended use).
Wei teaches soluble PH20 polypeptides, teaches that PH20 polypeptides are human hyaluronidases, and teaches that hyaluronidases increase tissue permeability and increases the dispersion and delivery of therapeutic agents (Wei, [0006]-[0008]). Wei also teaches that PH20 is useful for treating tumors (Wei, [0017]). Therefore, a person having ordinary skill in the art would have been motivated by the teachings of Wang to include PH20 in a therapeutic composition for treating tumors.
The combined teachings of Frost and Wei do not disclose formulation for subcutaneous administration.
Ang teaches the subcutaneous administration of T cells or NK cells expressing a CAR (Ang, [0016], [0021], [00104]). Ang also teaches that modified cells can be administered via various routes and to various sites in order to achieve a particular effect and that a particular route can provide a more immediate and effective reaction, depending on the cancer (Ang, [00107]). Therefore, a person having ordinary skill in the art would have been motivated by the teachings of Ang to administer T cells or NK cells expressing a CAR subcutaneously depending on the cancer being treated.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have formulated the T cells and/or NK cells of Frost for subcutaneous administration as taught by Ang and to have included PH20 as taught by Wei in said formulation to arrive at the invention claimed in instant claim 69 with a reasonable expectation of success because they would have been motivated to do so to achieve particular therapeutic effects depending on the cancer being treated and to increases the dispersion and delivery of therapeutic agents respectively. There would have been a reasonable expectation of success in combining Frost, Wei, and Ang because the T cells and/or NK cells of Frost could readily be formulated for subcutaneous administration and adding PH20 as taught by Wei would reasonably be expected to increase the therapeutic effect of the cells.
Regarding claim 70, Frost teaches infusing 7 x 106 transduced cells to a 70 kg subject (Frost, [0131]). Frost does not explicitly teach a volume of 2 to 1,000mL.
However, Low teaches methods of treating patients with cancer by administering a composition comprising CAR T cells (Low, Abstract). Low teaches that suitable volumes for the cell compositions range from about 5mL to about 200mL containing 1 x 105 to about 1 x 1015 transduced CAR T cells (Low, page 38, lines 3-14).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have used a composition volume of at least about 5mL to about 200mL as taught by Low in the methods of Frost and to have arrived at the invention claimed in instant claim 70 with a reasonable expectation of success because they would have been motivated to do so by Low’s teaching of the suitability of said volumes for cell therapy. It is noted that instant claim 70 is directed to a composition and not a method of treatment. A person having ordinary skill in the art would understand that larger volumes than those stated in Low would be advantageous for multiple administrations of the about 5mL to about 200mL as taught by Low. Hence, the Examiner’s use of “at least” in the above rejection.
Regarding claim 71, Wei teaches stock solutions of PH20 at about 100 U/mL to about 20,000 U/mL and subcutaneous administration of about 10 U to about 5,000 U or more in volumes of about 0.01mL to about 50mL or more (Wei, [0262]). Thus, a person having ordinary skill in the art would understand the volumes taught by Wei to overlap with the volumes taught by Low for CAR T cells and for said volumes to correlate with a concentration range of PH20 of 50 to 5,000 units/mL.
Regarding claim 72, Wei teaches PH20.
Regarding claim 73, Frost teaches wherein at least 10, 20, or 25% of the T cells are transduced, thereby producing genetically modified T cells (Frost, [0483]).
Regarding claim 74, Frost teaches isolating T cells (lymphocytes) from peripheral blood (PBMCs) and modifying them via retroviral transduction (Frost, [0482]-[0484]).
Regarding claim 75, the T cells (lymphocytes) are contacted with a replication incompetent retroviral particle which comprises a polynucleotide and the polynucleotide comprises one or more transcriptional units operatively linked to a promoter active in T cells and wherein the polynucleotide further encodes a polypeptide (Frost, [0482]-[0485]). “associated with” as used in claim 75 is interpreted as encompassing “contact” as used in Frost.
Regarding claim 76, the polypeptide is a chimeric antigen receptor (CAR) (Frost, [0485]).
Regarding claim 77, the retrovirus comprises an activation element on its surface (Frost, [0485]).
Regarding claim 78, the retroviral particle of Frost is a lentiviral particle (Frost, [0489]).
Regarding claim 79, at least 80% of the transduced cells of Frost do not express the polypeptide because Frost teaches that about 5% do express said polypeptide (Frost, FIG. 23A, [0033]).
Regarding claim 80, Frost teaches that the T cells integrate the polynucleotide into their genome (Frost, [0583]). Frost also teaches wherein at least 10, 20, or 25% of the T cells are transduced, thereby producing genetically modified T cells (Frost, [0483]). Therefore, Frost teaches wherein at least 75% of the modified lymphocytes do not have the polynucleotide stably integrated into their genomes.
Regarding claim 81, Frost, Wei, Ang and Low do not teach at least 10% of the cells in the formulation form aggregates of T cells and/or NK cells that are at least 15μm in their smallest dimension.
Li teaches that activated T cells grow in clusters and that, with daily disaggregation via pipette mixing, the clusters can reach 2μm in diameter or 250μm in diameter (Li, page 4, paragraph 2). Li provides micrographs which depict the majority of cells as being part of the clusters (reading on “at least 10%” of the cells) (Li, fig. 1). Frost teaches that the T cells can be activated (Frost, [0004]-[0005]) and that the retroviral particles comprise an activation element capable of binding to and activating T cells (Frost, [0011], FIG. 1).
Therefore, a person having ordinary skill in the art would have understood from the teachings of Li and Frost that the activated T cells of Frost form clusters necessarily by nature of them being activated T cells. It would have been prima facie obvious to a person having ordinary skill in the art to have had at least 10% of the T cells in the formulation of Frost form cell aggregates of at least 15μm diameter and to have arrived at the invention claimed in instant claim 81 because they would have been motivated to do so because Li teaches that activated T cells naturally form clusters fitting these characteristics and Frost teaches to activate the T cells. Further, there would have been a reasonable expectation of success insofar as activating T cells with a retroviral particle comprising an activating element as taught by Frost would reasonably result in the formation of T cell aggregates.
Regarding claim 82, Frost teaches infusing 7 x 106 transduced cells to a 70 kg subject (Frost, [0131]), and Low teaches that suitable volumes for the cell compositions range from about 5mL to about 200mL containing 1 x 105 to about 1 x 1015 transduced CAR T cells (Low, page 38, lines 3-14).
Regarding claim 83, Wei teaches devices for delivery (Wei, [0101],[0254]), and teaches injection devices such as a needle so as to facilitate administration (e.g. sub-epidermal administration) (Wei, [0233], [0265]).
Regarding claim 84, Frost, Wei, Low, Ang, and Li are silent as to viability.
However, viable cell counting is well within the level of ordinary skill in the art for cell therapies (See for example Frost, [0684]), and the methods and compositions utilizing CAR T cells of Frost, Low, Ang, and Li are taught in the context of cell therapy. A person having ordinary skill in the art would readily understand that maximizing the number of viable cells in a therapeutic composition is desirable for maximizing the therapeutic effects of said composition and it is well within the level of ordinary skill in the art to count and select for viable cells in a cell composition to approach viable cell percentages of at least 60%.
Regarding claim 85, Low teaches infusible CAR-expressing cytotoxic T lymphocyte compositions comprising albumin and DMSO (Low, page 37, lines 20-33).
Low does not teach precise amounts for the albumin or the DMSO beyond stating “2% human serum albumin.” It is noted that, "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A). In this case, Low teaches the general conditions of an infusible composition comprising CAR T cells, and the level of ordinary skill in the art for cell therapeutics encompasses the variation of infusion components to optimize therapeutic effects. Thus, it is not inventive to discover the optimal range of albumin and DMSO by routine experimentation. Regarding the pH, Frost teaches the co-administration of pH-modulating agents with CAR T-cells and teaches tumor microenvironment-restricted CARs that are more active at lower pH levels of 5.8-7.0 and less active at physiological pH levels of 7.2-7.8 (Frost, Abstract, [0432], [0437]). Ang teaches that the pH of a pharmaceutical composition comprising CAR T cells can be adjusted according to well-known parameters (Ang, 0047]). Thus, the CAR T cells of Frost and Ang are taught as being able to be formulated at a pH range spanning 5.8-7.8 which encompasses well known physiological levels.
Regarding claim 86, Ang teaches that any and all aqueous solvents, non-aqueous solvents, isotonic agents and other component categories may be used as a pharmaceutically acceptable carrier and teaches sodium chloride as one such example (Ang, [0047]). Wei teaches adding potassium chloride to an infusion fluid (Wei, [0328]), teaches pharmaceutically acceptable compositions comprising magnesium carbonate, and “other such agents” (Wei, [0229]), and teaches sodium acetate (Wei, [0236]). Low teaches adding gluconate salts to the CAR T cell compositions (Low, page 32, lines 5-12). A person having ordinary skill in the art would understand magnesium chloride to fall within the “other such agents” taught by Wei and would understand sodium gluconate to be the salt of gluconate. Thus, the combined teachings of Ang, Wei, and Low render obvious a formulation further comprising sodium chloride, potassium chloride, sodium acetate, sodium gluconate, and magnesium chloride.
Regarding claim 87, Frost teaches a method of treating a disease comprising introducing an expression vector comprising a polynucleotide sequence encoding a CAR to peripheral blood to produce genetically engineered cytotoxic cells, and administering said cells to a subject (Frost, [0476]). Frost also teaches contacting resting T cells and/or NK cells with replication-incompetent retroviral particles comprising a polynucleotide encoding one or more transcriptional units to produce genetically modified T cells and/or NK cells and administering said cells to a subject (Frost, [0479]). Frost also teaches that the T cells integrate the polynucleotide into their genome (Frost, [0583]). Frost also teaches wherein at least 10, 20, or 25% of the T cells are transduced, thereby producing genetically modified T cells (Frost, [0483]). Therefore, Frost teaches wherein at least 25% of the modified lymphocytes do not have the polynucleotide stably integrated into their genomes.
Frost does not teach subcutaneous administration or the specific step of collecting the cells to form a cell formulation. However, a person having ordinary skill in the art would understand that, following viral transduction, engineered T cells would need to be placed in a device for the administration of Frost to occur. Placing cells in a device for administration is encompassed by the broadest reasonable interpretation of “collecting”.
Ang teaches the subcutaneous administration of T cells or NK cells expressing a CAR (Ang, [0016], [0021], [00104]). Ang also teaches that modified cells can be administered via various routes and to various sites in order to achieve a particular effect and that a particular route can provide a more immediate and effective reaction, depending on the cancer (Ang, [00107]). Therefore, a person having ordinary skill in the art would have been motivated by the teachings of Ang to administer T cells or NK cells expressing a CAR subcutaneously depending on the cancer being treated.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have administered the T cells and/or NK cells of Frost subcutaneously as taught by to arrive at the invention claimed in instant claim 87 with a reasonable expectation of success because they would have been motivated to do so to achieve particular therapeutic effects depending on the cancer being treated. There would have been a reasonable expectation of success in combining Frost, and Ang because the T cells and/or NK cells of Frost could readily be formulated for subcutaneous administration.
Regarding claim 88, Frost teaches that immune cells comprises T cells as well as monocytes and teaches that the method does not include a step of removing monocytes (Frost, [0057], [0099], [0695]). Klieveland teaches that PBMCs include 10-20% monocytes generally (Klieveland, page 162, first paragraph). Thus, a person having ordinary skill in the art would have understood the modified cells of Frost to include 10% monocytes as in claim 88.
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.
Claim 87 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19 of copending Application No. 18/335000 in view of WO2018/009923 (Published: 11 January, 2018) (hereinafter “Frost”) (Of Record), and WO2019/165097 (Published: 29 August, 2019) (hereinafter “Ang”) (Of Record).
Copending claim 19 recites:
“A method for performing adoptive cell therapy on a subject, comprising:a) contacting a T cell and/or an NK cell from the subject ex vivo with replication incompetent recombinant retroviral particles, wherein the replication incompetent recombinant retroviral particles comprise: i. a polynucleotide comprising one or more transcriptional units, wherein each of the one or more transcriptional units is operatively linked to a promoter active in T and/or NK cells, and wherein the one or more transcriptional units encode a first engineered polypeptide; and ii. an activation element on the surfaces of the replication incompetent recombinant retroviral particles, wherein the activation element is fused to a membrane attachment sequence, wherein said contacting facilitates transduction of the T cell and/or NK cell; b) expanding the transduced T cell and/or NK cell ex vivo for fewer than 4 cell divisions; and c) introducing the expanded T cells and/or NK cells into the subject, thereby performing adoptive cell therapy on the subject.”
Instant claim 87 recites:
“A method of administering modified T cells and/or NK cells to a subject, comprising: a. contacting T cells and/or NK cells ex vivo with replication incompetent recombinant retroviral particles comprising a polynucleotide encoding a transgene, wherein the recombinant retroviral particles modify the T cells and/or NK cells; b. collecting the modified T cells and/or NK cells to form a cell formulation comprising a suspension of the modified T cells and/or NK cells; and c. administering the cell formulation to a subject subcutaneously, wherein at least 25% of the modified T cells and/or NK cells in the cell formulation do not have the polynucleotide stably integrated into their genomes.”
Instant claim 87 is narrower than copending claim 19 in that it requires subcutaneous administration and at least 25% of the modified cells do not have the polynucleotide stably integrated into their genomes.
Frost discloses methods for genetically modifying T cells and/or NK cells (lymphocytes) with replication incompetent recombinant retroviruses, T cell and/or NK cell products of these methods, and methods of using such cells as an adoptive cell therapy (Frost, Abstract). Frost teaches modifying T cells to produce CAR T cells and their use for treating tumors (Frost, Abstract, [0005], [0429]). Frost teaches that the T cells integrate the polynucleotide into their genome (Frost, [0583]). Frost also teaches wherein at least 10, 20, or 25% of the T cells are transduced, thereby producing genetically modified T cells (Frost, [0483]). Therefore, Frost teaches wherein at least 25% of the modified lymphocytes do not have the polynucleotide stably integrated into their genomes. Ang teaches the subcutaneous administration of T cells or NK cells expressing a CAR (Ang, [0016], [0021], [00104]). Ang also teaches that modified cells can be administered via various routes and to various sites in order to achieve a particular effect and that a particular route can provide a more immediate and effective reaction, depending on the cancer (Ang, [00107]). Therefore, the invention claimed in instant claim 87 would have been obvious to a person having ordinary skill in the art in view of copending claim 19, Frost, and Ang.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 69-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-27 of U.S. Patent No. 11,325,948 in view of WO2018/009923 (Published: 11 January, 2018) (hereinafter “Frost”) (Of Record), US2010/0143457 (Published: 10 June, 2010) (hereinafter “Wei”), WO2019/165097 (Published: 29 August, 2019) (hereinafter “Ang”) (Of Record), WO2017/177149 (Published: 12 October, 2017) (hereinafter “Low”), and Li et al. Autoimmunity 52.3 (2019): 102-107. (published: 25 June, 2019) (hereinafter “Li”) (Of Record).
Reference Patent claim 23 recites:
“A method for genetically modifying a T cell of a subject, wherein the method comprises: contacting a population of T cells comprising the T cell ex vivo, with a population of replication incompetent recombinant retroviral particles according to claim 16, wherein said contacting is performed for less than 12 hours to facilitate membrane fusion of the T cell to the replication incompetent recombinant retroviral particle, thereby genetically modifying the T cell.”
Instant claim 69 recites:
“A cell formulation for subcutaneous administration, comprising modified lymphocytes and/or tumor infiltrating lymphocytes and wherein the cell formulation further comprises a recombinant hyaluronidase.”
Instant claim 87 recites:
““A method of administering modified T cells and/or NK cells to a subject, comprising: a. contacting T cells and/or NK cells ex vivo with replication incompetent recombinant retroviral particles comprising a polynucleotide encoding a transgene, wherein the recombinant retroviral particles modify the T cells and/or NK cells; b. collecting the modified T cells and/or NK cells to form a cell formulation comprising a suspension of the modified T cells and/or NK cells; and c. administering the cell formulation to a subject subcutaneously, wherein at least 25% of the modified T cells and/or NK cells in the cell formulation do not have the polynucleotide stably integrated into their genomes.”
Instant claim 69 is a species of product produced by the method claimed in reference patent claim 23 insofar as the genetically modified T cells produced by said method are equivalent to the instantly claimed modified lymphocytes and all that is missing from the reference claim is formulation for subcutaneous administration and a recombinant hyaluronidase. Frost discloses methods for genetically modifying T cells and/or NK cells (lymphocytes) with replication incompetent recombinant retroviruses, T cell and/or NK cell products of these methods, and methods of using such cells as an adoptive cell therapy (Frost, Abstract). Frost teaches modifying T cells to produce CAR T cells and their use for treating tumors (Frost, Abstract, [0005], [0429]). Therefore, Frost teaches modifying lymphocytes more generally with the same replication-incompetent recombinant retrovirus. Ang teaches the subcutaneous administration of T cells or NK cells expressing a CAR (Ang, [0016], [0021], [00104]). Ang also teaches that modified cells can be administered via various routes and to various sites in order to achieve a particular effect and that a particular route can provide a more immediate and effective reaction, depending on the cancer (Ang, [00107]). Wei teaches soluble PH20 polypeptides, teaches that PH20 polypeptides are human hyaluronidases, and teaches that hyaluronidases increase tissue permeability and increases the dispersion and delivery of therapeutic agents (Wei, [0006]-[0008]). Wei also teaches that PH20 is useful for treating tumors (Wei, [0017]). Therefore, instant claim 69 would have been obvious to a person having ordinary skill in the art in view of reference claim 23, Frost, Wei, and Ang. Regarding instant claim 87, the claimed limitations can be found throughout reference claims 23-27. Dependent claim limitations found in instant claims 70-86 can be found throughout the reference claims in view of Frost, Wei, Ang, Low, and Li.
Conclusion
No claim is allowed.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634