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
An amendment was received on 06/29/2026.
Claims 1-2, 6-7, 10-15, and 24-28 are pending, all of which have been considered on the merits.
All arguments have been fully considered. This status of each prior ground of rejection is set forth below.
Response to Arguments / Status of Rejections
RE: Objection of claim 4:
The cancellation of claim 4 renders the objection thereof moot.
RE: Rejections of claims 1-7 and 10-14 under 35 U.S.C. 112 (b):
The cancellation and/or amendments to the claims overcome the basis of the prior rejections of record. The rejections are withdrawn.
RE: Rejections of claims 1-4,6,7,10-15, and 24-28 under 35 U.S.C. 102(a)(1) over Mullinax et al (WO 2020/068816):
The cancellation and/or amendments to the claims overcome the basis of the prior rejections of record. Specifically, while Mullinax et al teach a combination of enzymes can be used to digest the tumor, they do not teach the species of enzymes claimed with sufficient specificity to anticipate (Mullinax only generically suggests hyaluronidase, collagenase and/or DNase, not the specific versions claimed).
The rejections are withdrawn.
RE: Rejection of claim 5 under 35 U.S.C. 103 over Mullinax et al (WO 2020/068816) in view of Locke et al (2019), Shaw et al (2012), Chong et al (2016):
The cancellation of claim 5 renders the objection thereof moot.
Due to the limitation of claim 5 that was cancelled being included in the claim 1, the arguments to the rejection are being addressed.
Applicants’ traverse the rejection on the grounds that the none of the prior art cited alone or in combination does not account for all the limitations of claim 1 or 15 and any dependent on. Applicants assert that the combination of Mullinax, Locke et al, Shaw et al, and Chong et al, does not disclose or teach the step in claim 1, digesting the one or more tissue sample with a combination of two or more enzymes selected from the group consisting of human hyaluronidase, dornase alfa, and collagenase clostridium histolyticum.
In response, these arguments are not found to be persuasive.
Applicants argue that Mullinax et al does not teach the step in claim 1 recited above but as in the rejection provided below, Mullinax et al discloses a method such that one or more tissue samples is digested with one or more enzymes (See, p1-2 ¶5) and that the digestion solution can be a combination of collagenase, hyaluronidase and/or DNAse enzymes (See, p10 ¶19). While Mullinax et al teach a combination of enzymes can be used to digest the tumor, they do not teach the species of enzymes claimed with sufficient specificity to anticipate (Mullinax only generically suggests hyaluronidase, collagenase and/or DNase, not the specific versions claimed). Locke et al teaches a human hyaluronidase. Shaw et al teaches of a human DNAse that goes by the generic name dornase alfa. Chong et al teaches of clostridium histolyticum. Therefore, the combination of established enzymes for the use of the method disclosed by Mullinax et al would be obvious (See modified rejection below).
Therefore, the rejection has been modified to address the new limitation.
RE: Provisional rejection of claims 1,2,4,11-15 under 35 U.S.C 101, Statutory Double Patenting, as having the same scope of the invention of claims 1-3 and 11-15 of co-pending Application No. 18/555,584:
The cancellation and/or amendments to the claims overcome the basis of the prior rejections of record. The rejections are withdrawn.
RE: Provisional rejection of claims 3,5-7,10, and 24-28 under Non-Statutory Double Patenting, of claims 3, 5-10, 14, 15, and 24 of co-pending Application No. 18/555,584:
The cancellation and/or amendments to the claims overcome the basis of the prior rejections of record. Specifically, the amendments to claim 1. While Mullinax et al teach a combination of enzymes can be used to digest the tumor, they do not teach the species of enzymes claimed with sufficient specificity to anticipate (Mullinax only generically suggests hyaluronidase, collagenase and/or DNase, not the specific versions claimed).
Therefore, the rejection has been modified to address the new limitation.
RE: Provisional rejection of claims 1-6,10-15, and 24-28 under Non-Statutory Double Patenting, claims 1-2, 10-13, and 20-24 of co-pending Application No. 17/279,327:
The cancellation and/or amendments to the claims overcome the basis of the prior rejections of record. Specifically, the amendments to claim 1. While Mullinax et al teach a combination of enzymes can be used to digest the tumor, they do not teach the species of enzymes claimed with sufficient specificity to anticipate (Mullinax only generically suggests hyaluronidase, collagenase and/or DNase, not the specific versions claimed).
Therefore, the rejection has been modified to address the new limitation.
RE: Provisional rejection of claim 15 under Non-Statutory Double Patenting, as of claim 12 of co-pending Application No. 16/610,681:
The cancellation and/or amendments to the claims overcome the basis of the prior rejections of record. Specifically, the amendments to claim 15, that now includes obtaining one or more tissue samples from a subject, digesting in combination of enzymes, is sufficient to differentiate the instant application from the co-pending application.
Therefore, the rejections are withdrawn.
Modified Rejections and New Grounds of Rejections
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 6-7 and 10 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.
Instant claim 6 is dependent upon cancelled claim 3. This therefore renders the scope of the claim indefinite, as the metes and bounds of the claim cannot be readily determined.
As claims 7 and 10 dependents upon claim 6, they inherit the deficiencies.
For compact prosecution, claim 6 is being interpreted as depending on claim 1.
Appropriate correction or clarification is required.
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.
Claims 1, 6-7, 11-14, and 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Mullinax et al (WO 2020/068816 A1; as cited in the IDS filed on 08/28/2024) in view of Locke et al ( Drug delivery, 2019), Shaw et al (Human gene therapy methods,2012), and Chong et al (Translational andrology and urology, 2016). (Locke, Shaw, and Chong cited in previous Office Action dated 01/28/2026).
Mullinax et al discloses methods for rapidly expanding tumor infiltrating lymphocytes using digested tumor cells (See, Abstract).
Regarding claim 1: Mullinax et al discloses a method related to rapidly produce an expanded tumor infiltrating lymphocyte (TIL) population from bulk non purified tumor digests (See, p1 ¶3). They also disclose a method of rapidly producing an expanded tumor infiltrating lymphocytes (TIL) population for us in adoptive cell therapy comprising culturing bulk, non-purified tumor digest from the subject in a culture medium comprising IL-2 in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and/or specificity (See, p1 ¶4). Mullinax et al discloses that the term “subject” can be human (See, p5 ¶25). This reads on, a method of producing an expanded tumor reactive TIL population for use in adoptive cell therapy… and c) culturing bulk, non-purified tumor digest from a human subject in a culture medium comprising IL-2 in an amount effective to expand TIL with enriched tumor reactivity.
Mullinax et al discloses that the method further comprising…obtaining said one or more tissue samples comprising TILs from the subject; and digesting the one or more tissue samples…with one or more enzymes (See, p1-2 ¶5). This reads on, …a) obtaining one or more tissue samples from a subject, b) digesting the one or more tissue samples with a combination of two or more enzymes.
Mullinax et al also discloses that the disclosed methods can comprise placing the tissue sample directly into a digestion solution (such as, collagenase enzymes, hyaluronidase, and/or DNase)(See, p10 ¶19).
Mullinax et al are silent about the specific enzymes used in method.
However, Locke et al teaches that there is a US Food and Drug Administration (FDA) approved recombinant human hyaluronidase PH20 enzyme, HYLENEX® (See, abstract). Shaw et al teaches that PULMOZYME® is a USFDA approved human DNase (See, abstract). Chong et al teaches XIAFLEX® is a USFDA approved agent of Clostridium histolyticum collagenase (See, abstract). The brand name drugs are non-generic versions of hyaluronidase, DNase, and collagenase, required by Mullinax et al.
The specification of the instant application notes that PULMOZYME® is a DNAse also by the name of dornase alfa and XIAFLEX® is a collagenase clostridium histolyticum (See, Instant specification p 2).
Given that Mullinax et al teaches the use generic enzymes in their methods and Locke et al, Shaw et al, and Chong et al teach example of brand name enzymes of the generics, there was a reasonable expectation that they would work equivalently. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Regarding claim 2, following the discussion above, Mullinax et al disclosed a method of rapidly producing an expanded TIL population for us in adoptive cell therapy comprising culturing bulk, non-purified tumor digest from the subject in a culture medium comprising IL-2 in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and/or specificity (See, p1 ¶4). This reads on, wherein the expanded TIL population also has enriched tumor specificity.
Regarding claim 6, following the above discussion, Mullinax et al discloses digesting the one or more tissue samples (including, but not limited to one or more biopsies (such as, core biopsies) and/or or more surgical resections) (See, p1-2 ¶5). This reads on, wherein the one or more tissue samples comprise one or more core biopsy tissue samples or one of more surgical resections.
Regarding claim 7, following the above discussion, Mullinax et al discloses methods of any preceding aspect, further comprising performing one or more biopsies (such as, for example, core biopsies and/or surgical resections) before plating the TILs (See, p2 ¶7). This reads on, the method of claim 6, further comprising performing one or more biopsies or one of more surgical resections before digesting the tissue sample.
Regarding claim 10, following the above discussion, Mullinax et al discloses methods of any proceeding aspect, wherein the one or more core biopsies are digested directly from the patient without disaggregation of the specimen (See p2 ¶6) This reads on, wherein the one or more core biopsies or one or more surgical resections are digested without disaggregating the specimen.
Regarding claim 11, following the above discussion, Mullinax et al discloses culturing the cells from biopsy in a complete media comprising IL-2 (See, p9 ¶13). This reads on, wherein the culture medium is complete media.
Regarding claim 12, following the above discussion, Mullinax et al discloses methods can further comprise harvesting the expanded TIL cells (See. p9 ¶13). This reads on, the method of claim 1, further comprising harvesting the expanded TIL population.
Regarding claim 13, following the above discussion, Mullinax et al discloses the present methods decreases the expansion time to less than 5 weeks (See, p10 ¶20). This reads on, wherein the TILs are cultured in media comprising IL-2 for 5 weeks or less.
Regarding claim 14, following the above discussion, Mullinax et al discloses methods of treating a cancer in a subject comprising administering to the subject the rapidly expanded TILs of any preceding aspect (See, p2 ¶9). This reads on, a method of treating a cancer in a subject comprising administering to the subject an expanded TIL population made by the method of claim 1.
Regarding claim 15, following the above discussion, Mullinax et al discloses methods of treating cancer in a subject, this reads on, a method of treating cancer in a human subject comprising…
The method comprises treating cancer in a subject comprising culturing bulk non-purified tumor digests from the subject in a culture medium comprising IL-2 in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity; this reads on, c) culturing bulk, non-purified tumor digest from the subject in a culture medium comprising IL-2 in an amount effective to expand TILs with enriched tumor-reactivity and/or specificity….
harvesting the expanded TIL cells; this reads on, …c)… harvesting the expanded TIL cells… Then adoptively transferring to the subject the expanded TILs (See, p2 ¶9). This reads on, d) adoptively transferring to the subject the expanded TILs.
Mullinax et al discloses that the term “subject” can be human (See, p5 ¶25). Mullinax et al discloses the method of treating cancer in a subject further comprises obtaining one or more tissues samples, including one or more biopsies (core biopsies) and or or one or more surgical resections; digesting the one or more samples with one or more enzymes (See, p2 ¶9). This reads on, a) obtaining one or more tissue samples from a subject… b) digesting the one or more tissue samples with a combination or two or more enzymes…
Mullinax et al are silent about the specific enzymes used in method.
However, Locke et al teaches that there is a US Food and Drug Administration (FDA) approved recombinant human hyaluronidase PH20 enzyme, HYLENEX® (See, abstract). Shaw et al teaches that PULMOZYME® is a USFDA approved human DNase (See, abstract). Chong et al teaches XIAFLEX® is a USFDA approved agent of Clostridium histolyticum collagenase (See, abstract). The brand name drugs are non-generic versions of hyaluronidase, DNase, and collagenase, required by Mullinax et al.
The specification of the instant application notes that PULMOZYME® is a DNAse also by the name of dornase alfa and XIAFLEX® is a collagenase clostridium histolyticum (See, Instant specification p 2).
Given that Mullinax et al teaches the use generic enzymes in their methods and Locke et al, Shaw et al, and Chong et al teach example of brand name enzymes of the generics, there was a reasonable expectation that they would work equivalently. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Regarding claim 24, following the discussion above, Mullinax et al discloses a non-limiting list of different types of cancers is as follows… carcinomas of solid tissues (See, p12-13 ¶28). This reads on, wherein the cancer is a solid tumor.
Regarding claims 25-26. following the discussion above, Mullinax et al discloses expanded TIL population can be used for the treatment of cancer (for example, a soft tissue sarcoma (See, p2 ¶9). This reads on, wherein the cancer is a sarcoma of claim 25 and wherein the sarcoma is a soft tissue sarcoma of claim 26.
Regarding claim 27, following the discussion above, Mullinax et al discloses expanded TIL population can be used for the treatment of cancer (for example, a soft tissue sarcoma (such as, for example but not limited to, fibrotic sarcomas (See, p2 ¶9). This reads on, wherein the soft tissue sarcoma is a fibrotic sarcoma.
Regarding claim 28, following the discussion above, Mullinax et al discloses expanded TIL population can be used for the treatment of cancer (for example, a soft tissue sarcoma(such as, for example but not limited to, fibrotic sarcomas including atypical lipomatous tumor, well-differentiated liposarcoma, myxofibrosarcoma, leiomyosarcoma, solitary fibrous tumor, and leiomyosarcoma) any connective tissue neoplasm, or bone sarcomas. (See, p2 ¶9). This reads on, wherein the fibrotic sarcomas…atypical lipomatous tumor, solitary fibrous tumor, leiomyosarcoma.
Therefore, claims 1-2,6-7,10-15, and 24-28 are rejected as being rendered obvious by Mullinax et al (WO 2020/068816 A1; as cited in the IDS filed on 08/28/2024) in view of Locke et al ( Drug delivery, 2019), Shaw et al (Human gene therapy methods,2012), and Chong et al (Translational andrology and urology, 2016).
Non-statutory Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1-2,6-7,10-15, and 24-28 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-2,6-8,11-15, and 24 of co-pending Application No. 18/555,584 (reference application).
Regarding claim 1, reference claim 1 recites a method of producing an expanded tumor reactive tumor infiltrating lymphocytes (TIL) population for use in adoptive cell therapy comprising: (a) obtaining a bulk, non-purified tumor digest from one or more tissue samples: (b) digesting the bulk, non- purified tumor digest with one or more human or humanized enzymes, wherein the one or more human or humanized enzymes comprises collagenase, hyaluronidase, and/or DNAse; and (c) culturing the bulk, non-purified tumor digest in a culture medium comprising IL-2 in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor- reactivity, wherein the digesting in step (b) improves the total number of viable cells following digest, the percentage of digest viability, and/or the number of total CD8+ T cells following digest, compared to a digesting not using the one or more human or humanized enzymes. Although the claims at issue are not identical, they are not patentably distinct from each other because reference claim 1 includes all the limitations of the instant claim 1. The human or humanized enzymes, hyaluronidase and DNAse read on the human hyaluronidase of instant claim 1 and the dornase alfa respectively (See, Instant Specification p6 ¶5-6).
Regarding claim 2, following the discussion above, reference claim 2 recites the method of claim 1, wherein the expanded TIL population also has enriched tumor specificity. Although the claims at issue are not identical, they are not patentably distinct from each other because reference claim 2 reads all the limitations of the instant claim 2.
Regarding claim 6, reference claim 6 recites the method of claim 1, wherein the one or more tissue samples comprise one or more core biopsy tissue samples. Reference claim 8 recites the method of claim 1, wherein the one or more tissue sample comprise one or more surgical resections. Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claims 6 and 8 reads on instant claim 6.
Regarding claim 7, reference claim 7 recites the method of claim 6, further comprising performing one or more core biopsies before digesting the tissue sample. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 7 reads on all the limitations of instant claim 7.
Regarding claim 10, reference claim 10 recites the method of claim 1, wherein the one or more tissue samples are digested without disaggregating the specimen. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 10 reads on all the limitations of instant claim 10.
Regarding claim 11, reference claim 11 recites the method of claim 1, wherein the culture medium is complete media. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 11 reads on all the limitations of instant claim 11.
Regarding claim 12, reference claim 12 recites the method of claim 1, further comprising harvesting the expanded TIL population. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 12 reads on all the limitations of instant claim 12.
Regarding claim 13, reference claim 13 recites the method of claim 1, wherein the TILS are cultured in media comprising IL-2 for 5 weeks or less. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 13 reads on all the limitations of instant claim 13.
Regarding claim 14, reference claim 14 recites a method of treating a cancer in a subject comprising administering to the subject an expanded TIL population made by the method of claim 1. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 14 reads on all the limitations of instant claim 14.
Regarding claim 15, reference claim 15 recites a method of treating cancer in a human subject comprising;(a) obtaining a bulk, non-purified tumor digest from one or more tissue samples from the human subject: (b) digesting the bulk, non-purified tumor digest with one or more human or humanized enzymes, wherein the one or more human or humanized enzymes comprises collagenase, hyaluronidase, and/or DNAse: (c) culturing the bulk, non-purified tumor digest in a culture medium comprising IL-2 in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and/or specificity; (d)harvesting the expanded TIL cells; and (e)adoptively transferring to the subject the expanded TILs, wherein the digesting in step (b) improves the total number of viable cells following digest, the percentage of digest viability, and/or the number of total CD8+ T cells following digest, compared to a digesting not using the one or more human or humanized enzymes. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 15 includes all the limitations of the instant claim 15. The human or humanized enzymes, hyaluronidase and DNAse read on the human hyaluronidase of instant claim 15 and the dornase alfa respectively (See, Instant Specification p6 ¶5-6).
Regarding claim 24, reference claim 24 recites the method claim 15,wherein the cancer is a solid tumor. Reference claim 15 recites the limitations needed for the instant claim 24 (see above), therefore although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claims 15 and 24 renders the instant claim 24 obvious.
Regarding claims 25-28, reference claim 14 recites a method of treating a cancer in a subject comprising administering to the subject an expanded TIL population made by the method of claim 1. Reference claims 15 and 24 are recited above. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 14-15 combined with the recitations of claims 24 (see above) is identical in scope to instant claims 25-28 due to the limitations of instant claims 25-28 are solid tumors and cancers, thus rendered obvious by the reference claims.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1,6-7,11-13, and 24-28 provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1,2,10-13, and 20-24 of co-pending Application No. 17/279,327 (reference application) in view of Locke et al ( Drug delivery, 2019).
The teachings of Locke et al are set forth above.
Regarding claims 1: Reference claim 1 recites a method comprising rapid expansion (REP) of a tumor infiltrating lymphocytes (TIL) population for use in adoptive cell therapy, the method comprising:(a) obtaining one or more tissue samples from one or more biopsies and/or surgical resections of a tumor in a subject, without fragmentation; (b) digesting the one or more core biopsy tissue samples with one or more enzymes to form a bulk, non-purified tumor digest; and (c) expanding the TILs directly from the bulk, non-purified tumor digest in a complete culture medium comprising of IL-2. Reference claim 2 recites the method of claim 1, wherein the one or more enzymes comprise one or more collagenase enzymes.
Although the claims at issue are not identical, they are not patentably distinct from each other because the active steps of the method in the reference application read on the steps of claim 1 of instant application. The reference application differs from the instant application in that the reference application claims do not specify the type of collagenase enzyme used.
Locke et al teaches that there is a US Food and Drug Administration (FDA) approved recombinant human hyaluronidase PH20 enzyme, HYLENEX® (See, abstract).
Given that reference application claims teaches the use generic enzymes in their methods and Locke et al teaches an example of brand name enzymes that are human hyaluronidase of the generics, there was a reasonable expectation that they would work equivalently. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Regarding claims 6 and 7: Reference claim 1 recites …(a) obtaining one or more bulk, tissue sample; (b) digesting the one or more tissue samples with one or more enzymes to form a bulk, non-purified tumor digest… Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 6 and 7 of instant application. Reference application does not indicate that the samples can be from one or more surgical resections but the reference claim does read on the use of one or more tissue samples of the instant claim. Therefore, they are not patentably distinct because instant claim 6 is obvious in view of the reference claim. The reference claim recites obtaining the sample before digesting, which renders claim 7 obvious.
Regarding claim 11: Reference claim 1 recites …(c) expanding the TILs directly from the bulk, non-purified tumor digest in a complete culture medium comprising of IL-2. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 11 of instant application for the use of complete culture medium. Therefore, they are not patentably distinct because instant claims 11 is obvious in view of the reference claim.
Regarding claim 12: Reference claim 10 recites the method of claim 1, further comprising harvesting the expanded TIL population. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 12 of instant application. Therefore, they are not patentably distinct because instant claims 12 is obvious in view of the reference claim.
Regarding claim 13: Reference claim 11 recites the method of claim 1, wherein the TILs are cultured in step (c) for 5 weeks or less. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 13 of instant application. The culture media in step (c) is a complete medium comprising IL-2. Therefore, they are not patentably distinct because instant claims 13 is obvious in view of the reference claim.
Regarding claim 14: Reference claim 12 recites a method of treating a cancer in a subject comprising administering to the subject a rapidly expanded TIL population made by the method of claim 1. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 14 of instant application. Therefore, they are not patentably distinct because instant claims 14 is obvious in view of the reference claim.
Regarding claim 24: Reference claim 20 recites the method of claim 13, wherein the cancer is a solid tumor. Reference 13 is recited above, the combination of reference claims 13 and 20 recite the limitations of needed for the instant claim 24, therefore although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claims 13 and 20 renders the instant claim 24 obvious.
Regarding claim 25: Reference claim 21 recites the method of claim 20, wherein the cancer is a sarcoma. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 25 of instant application. Therefore, they are not patentably distinct because instant claims 25 is obvious in view of the reference claim.
Regarding claim 26: Reference claim 22 recites the method of claim 21, wherein the sarcoma is a soft tissue sarcoma. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 26 of instant application. Therefore, they are not patentably distinct because instant claims 26 is obvious in view of the reference claim.
Regarding claim 27: Reference claim 23 recites the method of claim 22, wherein the soft tissue sarcoma is a fibrotic sarcoma. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 27 of instant application. Therefore, they are not patentably distinct because instant claims 27 is obvious in view of the reference claim
Regarding claim 28: Reference claim 24 recites the method of claim 23, wherein the fibrotic sarcoma is selected from the group consisting of atypical lipomatous tumor, well-differentiated liposarcoma, myxofibrosarcoma, solitary fibrous tumor, and leiomyosarcoma. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application read on the steps of claim 28 of instant application. Therefore, they are not patentably distinct because instant claims 28 is obvious in view of the reference claim
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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