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
This application is a national stage entry under 35 USC 371 of PCT/US2022/024804 (filed 4/14/2022). Acknowledgement is made of Applicants’ claim for benefit to US Provisional applications 63/176,177 (filed on 04/16/2021) and 63/180,250 (filed on 04/27/2021).
Claim Status
A preliminary amendment was received on 10/16/2023. Claims 1-3,6-16, and 19-24 are pending, all of which have been considered on the merits.
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 1-3 and 6-14 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.
The term “rapidly ” in claim 1-3 and 6-14 is a relative term which renders the claim indefinite. The term “rapidly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Regarding Claim 1-3 and 6-14, The phrase “rapidly producing” an expanded tumor reactive tumor infiltrating lymphocytes (TIL) population in claims 1-3 and 6-14 is ambiguous because neither the prior art nor the specification make clear what is included or excluded by the relative term “rapidly”.
For examination purposes with respect to prior art, any method that comprises of expanding a tumor reactive tumor infiltrating lymphocytes (TIL) population and meeting the recited active method steps will be considered within the metes and bounds of claim 1.
Claim 10 recites the limitation "wherein the one or more core biopsies or one or more surgical resections" in line 1-2. There is insufficient antecedent basis for this limitation in the claim. Biopsies and surgical resections are limitations in claims 6 and 8 respectfully, not claim 3, which claim 10 is dependent on.
Claim 23 recites the limitation “wherein the…or one or more surgical resections are digested without disaggregating the specimen” in line 2-3. There is insufficient antecedent basis for this limitation in the claim. Surgical resections are not a part of the limitations of claim 19, which 23 is dependent on.
Appropriate correction or clarification 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 1-3,6-16, 19-22, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mullinax et al (WO 2020/068816 A1; as cited in the IDS filed on 10/16/2023).
Mullinax et al discloses methods for rapidly expanding tumor infiltrating lymphocytes using digested tumor cells (See, Abstract).
Regarding Claim 1 and 2: Mullinax et al discloses a method related to rapidly producing an expanded tumor infiltrating lymphocyte (TIL) population from bulk non purified tumor digests (See, p1 ¶3). It is also disclosed 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 rapidly producing an expanded tumor reactive tumor infiltrating…”, the entirety of instant claim 1. This also reads on “ wherein the expanded TIL population also has enriched tumor specificity” of instant claim 2.
Regarding Claim 3: Following the above discussion, Mullinax et al discloses that the method further comprising…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). 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) These disclosures read on “obtaining one or more tissue samples from a subject and digesting the one or more tissue samples with one or more human or humanized enzymes…comprise of collagenase, hyaluronidase, and/or DNase” of instant claim 3.
Regarding Claims 6-9: 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, for example, core biopsies) and/or or more surgical resections)…(See, p1-2 ¶5). This reads on “comprise one or more core biopsy tissue samples” of instant claim 6. This reads on “one or more core biopsies before digesting…” of instant claim 7. This reads on “comprise one or more surgical resections” of instant claim 8. This also reads on “ one or more surgical resection before digesting..” of instant claim 9.
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 “one or more core biopsies… are digested without disaggregating the specimen” of the instant claim.
Regarding Claims 11 and 12: 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” of instant claim 11. Mullinax et al discloses methods can further comprise harvesting the expanded TIL cells (See. p9 ¶13). This reads on “…comprising harvesting the expanded TIL population” of instant claim 12.
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” of the instant claim.
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 “…comprising administering to the subject a rapidly expanded TIL population…” of the instant claim.
Regarding Claim 15: Following the above discussion, Mullinax et al discloses methods of treating cancer in a subject comprising 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; harvesting the expanded TIL cells; adoptively transferring to the subject the expanded TILs (See, p2 ¶9). ). Mullinax et al discloses that the term “subject” can be human (See, p5 ¶25). This reads on the entirety of claim 15.
Regarding Claim 16: Following the above discussion, Mullinax et al discloses …the methods of treating a cancer can further comprise obtaining one or more tissue samples… digesting the one or more tissue samples with one or more enzymes (See, p2 ¶9) This reads on “comprising obtaining one or more tissue samples from a subject…digesting the one or more tissue samples with one or more human or humanized enzymes…” of the instant claim. Above discussion of claim 3 shows that Mullinax et al also discloses the use of “collagenase, hyaluronidase, and/or DNase” of the instant claim.
Regarding Claims 19-22: Following the above discussion, Mullinax et al discloses …the methods of treating a cancer can further comprise obtaining one or more tissue samples (including, but not limited to one or more biopsies (such as, core biopsies) and/or one or more surgical resections) from which bulk, non-purified tumor digest is derived or obtained…digesting the one or more tissue samples with one or more enzymes (See, p2 ¶9). This reads on “…comprise one or more core biopsy tissue samples” of instant claim 19. This reads on “… comprising one or more core biopsies before digesting the tissue sample” of instant claim 20. This reads on “comprise one or more surgical resections” of instant claim 21. This also reads on “comprising one or more surgical resection before digesting the tissue sample” of instant claim 22.
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 “where in the cancer is a solid tumor” of the instant claim, due to it being known in the art that a solid tissue carcinoma is a solid tumor.
Therefore claims 1-3,6-16, 19-22, and 24 are rejected as being anticipated by Mullinax et al.
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.
Claim 23 is 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 10/16/2023).
Following the discussion above, Mullinax et al discloses methods of treating cancer in a subject comprising treating cancer in a subject comprising culturing bulk non-purified tumor digests (… digesting the one or more tissue samples with one or more enzymes) 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; harvesting the expanded TIL cells; adoptively transferring to the subject the expanded TILs (See, p2 ¶9). Mullinax et al discloses …the methods of treating a cancer can further comprise obtaining one or more tissue samples… digesting the one or more tissue samples with one or more enzymes (See, p2 ¶9). Mullinax et al does not teach an embodiment, where in the cancer treatment method, the tissue that is digested without disaggregation of the specimen.
Mullinax et al does in another embodiment a method wherein the one or more core biopsies are digested directly from the patient without disaggregation of the specimen (See p2 ¶6).
It would have been prima facie obvious to a person of ordinary skill in the art to have modified the method of Mullinax et al of treating cancer by combining the digesting of the tissue samples directly from the patient without disaggregation of the specimen as also taught by Mullinax et al. This conclusion of obviousness is based on the teaching suggestion motivation rationale. One would have had a reasonable expectation of success combining the digestion of tissues teachings of Mullinax et al. to obtain TIL to treat cancer. These teachings read on wherein the one or more core biopsies or one or more surgical resections are digested without disaggregating the specimen of instant claim 23.
Therefore claim 23 is obvious over Mullinax et al.
Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-3 and 11-15 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-2,4,10-15, and 24 of co-pending Application No. 18/842,179 (reference application).
Regarding claim 1: The instant claim is identical in scope to claim 1 of the reference application, as both claims recite a method of rapidly producing an expanded tumor reactive tumor infiltrating lymphocytes (TIL) population for use in adoptive cell therapy comprising culturing bulk, non- purified tumor digest from a human subject in a culture medium comprising IL-2 in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity.
Regarding claim 2: The instant claim is identical in scope to claim 2 of the reference application, as both claims recite the method of claim 1, wherein the expanded TIL population also has enriched tumor specificity.
Regarding claim 3: The instant claim is identical in scope to claim 4 of the reference application, as both claims recite the method of claim 3, wherein the combination of two human or humanized enzymes; comprises at least one of the human or humanized enzymes is selected from the group consisting of collagenase, hyaluronidase, or DNase.
Regarding claim 11: The instant claim is identical in scope to claim 11 of the reference application, as both claims recite the method of any of claim 1,wherein the culture medium is complete media
Regarding claim 12: The instant claim is identical in scope to claim 12 of the reference application, as both claims recite the method of any of claim 1, further comprising harvesting the expanded TIL population.
Regarding claim 13: The instant claim is identical in scope to claim 13 of the reference application, as both claims recite the method of any of claim 1, wherein the TILs are cultured in media comprising IL-2 for 5 weeks or less.
Regarding claim 14: The instant claim is identical in scope to claim 14 of the reference application, as both claims recite 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.
Regarding claim 15: The instant claim is identical in scope to claim 15 of the reference application, as both claims recite a method of treating cancer in a human subject 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 (TILs) with enriched tumor- reactivity and/or specificity; harvesting the expanded TIL cells; and adoptively transferring to the subject the expanded TILs.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
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 6-10, 16, and 19-24 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 3,4,6,7, and 10 of co-pending Application No. 18/842,179 (reference application).
.
Regarding claims 6 and 8: Reference claim 6 recites the method of claim 3, wherein the one or more tissue samples comprise one or more core biopsy tissue samples or one of more surgical resections. Reference claim 4 recites the method of claim 3, wherein the combination of two human or humanized enzymes; comprises at least one of the human or humanized enzymes is selected from the group consisting of collagenase, hyaluronidase, or DNAse. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 4 combined with reference claim 6 renders instant claims 6 and 8 obvious as taught in Mullinax et al.
Regarding claims 7 and 9: Reference claim 7 recites the method of claim 6, further comprising performing one or more core biopsies or one of more surgical resections before digesting the tissue sample. Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claim 4 (see above) and reference claim 7 renders the two instant claims 7 and 9 obvious as taught in Mullinax et al.
Regarding claim 10: Reference claim 10 recites the method of claim 3,wherein the one or more core biopsies or one or more surgical resections 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 combined with the recitations of claims 3-4 (see above) is identical in scope to instant claim 10.
Regarding claim 16: Reference claim 15 recites a method of treating cancer in a human subject 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 (TILs) with enriched tumor- reactivity and/or specificity; harvesting the expanded TIL cells; and adoptively transferring to the subject the expanded TILs. Reference claim 4 recites the method of claim 3, wherein the combination of two human or humanized enzymes; comprises at least one of the human or humanized enzymes is selected from the group consisting of collagenase, hyaluronidase, or DNAse. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim 15 combined with the recitations of reference claim 4 is identical in scope to instant claim 16 and is rendered obvious as taught in Mullinax et al.
Regarding claims 19-22: Reference claims 4 recites the method of claim 3, wherein the combination of two human or humanized enzymes; comprises at least one of the human or humanized enzymes is selected from the group consisting of collagenase, hyaluronidase, or DNAse. Reference claim 6 recites the method of claim 3, wherein the one or more tissue samples comprise one or more core biopsy tissue samples or one of more surgical resections. Reference claim 7 recites the method of claim 6, further comprising performing one or more core biopsies or one of more surgical resections before digesting the tissue sample. Reference claim 15 recites the reference application, as both claims recite a method of treating cancer in a human subject 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 (TILs) with enriched tumor- reactivity and/or specificity; harvesting the expanded TIL cells; and adoptively transferring to the subject the expanded TILs. Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claims 4,6,7, and 15 renders the two instant claims 19-22 obvious as taught in Mullinax et al.
Regarding claim 23: Reference claims 4,6, and 15 are recited above. Reference claim 10 recites the method of claim 3,wherein the one or more core biopsies or one or more surgical resections are digested without disaggregating the specimen. Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claims 4,6,10, and 15 renders the instant claim 23 obvious as taught in Mullinax et al.
Regarding claim 24: Reference claim 24 recites the method claim 14,wherein the cancer is a solid tumor. Reference claim 15 recites the limitations of 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 as taught in Mullinax et al.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3,6, and 10-14 provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-3 and 10-12 of co-pending Application No. 17/279,327 in view of Mullinax et al (WO 2020/068816 A1; as cited in the IDS filed on 10/16/2023).
Regarding claim 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 bulk, non-purified tumor digests from a core biopsy tissue sample; (b) digesting the one or more core biopsy tissue samples with one or more enzymes to form a bulk, non-purified tumor digest, wherein the one or more core biopsy tissue samples are digested without disaggregating the one or more tissue samples (c) expanding the TILs directly from the bulk, non-purified tumor digest in a complete culture medium consisting of IL-2 in an amount effective to expand TILs with enriched tumor-reactivity.
The reference claim does not teach that the core biopsy tissue sample comes from a human subject.
Mullinax et al teaches a method related to rapidly producing an expanded tumor infiltrating lymphocyte (TIL) population from bulk non purified tumor digests (See, p1 ¶3). It is also disclosed 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).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the core biopsy tissue sample in the co-pending application in the context of rapid expansion of a tumor infiltrating lymphocytes (TIL) population with core biopsy tissue sample from a human subject, taught by Mullinax et al for a similar purpose. Both the co-pending application and Mullinax et al teach a method for rapid expansion of TIL population.
The use of human subject tissue sample in place of the unspecific core biopsy tissue samples in the co-pending application is a predictable use of prior art elements according to their established functions, leading to the predictable result of TIL population with enriched tumor-reactivity.
This rationale aligns with the principle of KSR for a simple substitution of one known element for another to obtain predictable results, see MPEP 2143.
Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application and the specificity of the source of the tissue sample used in a similar method read on the steps of claim 1 of instant application, thus instant claim 1 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 2: Following the discussion above, reference application claim 2 recites the method of claim 1, wherein an 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 the steps provided in the reference application and the limitations covered by Mullinax et al, read on the limitations of claim 2 of instant application, thus instant claim 2 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 3: Following the discussion above, reference claim 1 as recited above, (b) digesting the one or more core biopsy tissue samples with one or more enzymes to form a bulk, non-purified tumor digest, wherein the one or more core biopsy tissue samples.
The reference claim does not teach the use of human or humanized enzymes; comprising of collagenase, hyaluronidase, and or DNAse.
Mullinax et al discloses that the method further comprising…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). 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).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the enzymes in the co-pending application in the context digesting one or more core biopsy tissue samples with human or humanized enzymes, collagenase, hyaluronidase, and or DNAse taught by Mullinax et al for a similar purpose. Both co-pending application and Mullinax et al teach a method for rapid expansion of TIL population.
The use of human or humanized enzymes, collagenase, hyaluronidase, and or DNAse in place of the enzymes in co-pending application, is a predictable use of prior art elements according to their established functions, leading to the predictable result of TIL population with enriched tumor-reactivity.
This rationale aligns with the principle of KSR for a simple substitution of one known element for another to obtain predictable results, see MPEP 2143.
Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application and the specificity of the enzymes used in a similar method read on the steps of claim 3 of instant application, thus instant claim 3 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 6: Following the discussion above, reference claim 1 recites ..(b) digesting the one or more core biopsy tissue samples with one or more enzymes to form a bulk, non-purified tumor digest, wherein the one or more core biopsy tissue samples. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application and the specificity of tissue sample used in a similar method read on the steps of claim 6 of instant application, thus instant claim 6 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 10: Following the discussion above, reference claim 1 recites ...(b) digesting the one or more core biopsy tissue samples with one or more enzymes to form a bulk, non-purified tumor digest, wherein the one or more core biopsy tissue samples are digested without disaggregating the one or more tissue samples. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application and the specificity of tissue sample used in a similar method read on the steps of claim 10 of instant application, thus instant claim 10 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 11: Following the discussion above, reference claim 1 recites …(c) expanding the TILs directly from the bulk, non-purified tumor digest in a complete culture medium consisting of IL-2 in an amount effective to expand TILs with enriched tumor-reactivity. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps provided in the reference application and the specificity of tissue sample used in a similar method read on the limitations of claim 11 of instant application, thus instant claim 11 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 12: Following the discussion above, 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 and the specificity of tissue sample used in a similar method read on the limitations of claim 12 of instant application, thus instant claim 12 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 13: Following the discussion above, reference claim 11 recites the method of claim 1, wherein the TILs are cultured in media consisting of 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 steps provided in the reference application and the specificity of tissue sample used in a similar method read on the limitations of claim 13 of instant application, thus instant claim 13 is rendered obvious over the co-pending application in view of Mullinax et al.
Regarding claim 14: Following the discussion above, 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 and the specificity of tissue sample used in a similar method read on the limitations of claim 14 of instant application, thus instant claim 14 is rendered obvious over the co-pending application in view of Mullinax et al.
This is a provisional non-statutory double patenting rejection.
Claims 15-16,19, and 23- 24 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 13 and 20 of co-pending Application No. 17/279,327 (reference application).
Regarding claim 15: Reference claim 13 recites a method of treating cancer in a subject comprising (a) obtaining a bulk, non-purified tumor digest from a core biopsy tissue sample obtained from the subject, wherein a fine needle penetrates a tumor at a depth between about 15mm and 30mm, and wherein the needle aspirates the core biopsy tissue sample from the tumor; (b) expanding tumor infiltrating lymphocytes (TILs) directly from the bulk, non- purified tumor digest in a complete culture medium consisting of IL-2 in an amount effective to expand the TILs with enriched tumor- reactivity and/or specificity; (c) contacting an excess of the bulk, non-purified tumor digest with digestion solution to obtain additional TILs, wherein the digestion solution comprises one or more enzymes, and wherein the bulk, non-purified tumor digest that is digested without being disaggregated; (d) culturing and harvesting the TILs from step (b) and (c); and (e) adoptively transferring to the subject the TILs of step (d). The reference claim 13 provides a narrower limitation on the tumor digest and the core biopsy but this reads on the limitation of instant claim 15. 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 limitations of claim 15 of instant application. Reference application has further limitations of how to obtain the tissue sample but the product of the method, an adoptively transferable expanded TIL are not patentably distinct thus renders instant claim 15 obvious.
Regarding claim 16: Reference claim 13 recites a method of treating cancer in a subject…(c) contacting an excess of the bulk, non-purified tumor digest with a digestion solution to obtain additional TILs, wherein the digestion solution comprises one or more enzymes, and wherein the bulk, non-purified tumor digest that is digested without being disaggregated…. 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 16 of instant application. Reference application has further limitations of how the tissue sample is obtained but the product of the method, an adoptively transferable expanded TIL are not patentably distinct thus renders instant claim 16 obvious.
Regarding claim 19: Reference claim 13 recites a method of treating cancer in a subject…(a) obtaining a bulk, non-purified tumor digest from a core biopsy tissue sample obtained from the subject, wherein a fine needle penetrates a tumor at a depth between about 15mm and 30mm, and wherein the needle aspirates the core biopsy tissue sample from the tumor…. 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 19 of instant application. Reference application describes obtaining a core biopsy from the tissue sample and the product of the method, an adoptively transferable expanded TIL is not patentably distinct thus renders instant claim 19 obvious.
Regarding claim 23: Reference claim 13 recites wherein the one or more core biopsy tissue samples are digested without disaggregating the one or more tissue samples. The combination of reference claims 1 and 13 recite the limitations of needed for the instant claim 23, therefore although the claims at issue are not identical, they are not patentably distinct from each other because the combination of reference claims 1 and 13 renders the instant claim 23 obvious.
Regarding claim 24: Reference 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.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 15 is provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 12 of co-pending Application No. 16/610,681 (reference application).
Regarding claim 15: Reference claim 12 recites a method of treating cancer in a subject in need thereof, comprising: a) obtaining a tissue sample derived from a single core biopsy specimen from the subject; b) directly plating the tissue sample n a single well of a gas-permeable tissue culture multi-well plate; c) culturing a population of tumor infiltrating lymphocytes (TILs) from the tissue sample in a complete media comprising IL-2 for 5 weeks or less, wherein the complete media in the gas-permeable tissue culture multi-well plate is exchanged at least 2 times per week d) harvesting the expanded TIL population; and e) adoptively transferring the expanded TIL population to the subject. 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 15 of instant application. Reference application describes a method for treating cancer, further describes the culturing of the tissue sample in b) and c), and the product of the method, an adoptively transferable expanded TIL are not patentably distinct from instant claim 15. Therefore, instant claim 15 is rendered obvious over reference co-pending application.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633