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 .
Status of Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on 8 September, 2025. Claims 1-3, 6-11, 14, 17 – 21, 25, and 28 - 31 are currently pending. Claims 1, 3, 6, 8, 10, 14, 17, and 25 have been amended in the Applicant’s amendment filed 8 September 2025. No claims have been added or canceled in the Applicant’s amendment filed 8 September, 2025.
Applicant's election without traverse of Group I, claims 1, 3, 6 – 11, 14, 17 – 19, 21, and 25, drawn to a method of conditioning treatment for ACT; and the election of Species without traverse as follows:
Species (A): the CD27 antibody is a depleting antibody (claim 14);
Species (B): the genetically engineered T cells express a CAR or TCR (claim 7);
Species (C): the transferred T cells are genetically engineered T cells (claim 6); the reply filed 20 February, 2025.
Claims 2, 20, 28 – 31 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 3, 8, 9, and 10 – 11 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 6, 7, 14, 17 – 19, 21, and 25 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8 September, 2025 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed May 28, 2021, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2019/065375, filed December 10, 2019, which claims the benefit of Provisional Application 62/778,019, filed December 11, 2018.
Therefore, the earliest priority date is December 11, 2018.
Maintained Objections/Rejections
Nonstatutory Double Patenting
The rejection of claims 1, 6, 7, 14, 17 – 19, 21, and 25 is maintained on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1 - 19 of US Patent 9169325 B2 ( hereinafter referred to as ‘325), and further in view of Lotze et al. (hereinafter referred to as “Lotze”) (WO2018129332, published 12 July, 2018).
Claim 1 of ‘325 recites an isolated monoclonal antibody which binds to human CD27, wherein the antibody comprises a heavy chain CDR1, CDR2, and CDR3 (Seq ID No. 38 – 40, respectively), and a light chain CDR1, CDR2, and CDR3 (Seq ID No. 44 – 46 respectively). Seq ID No. 38 – 40 and 44 – 46 have a 100% alignment score to instantly recited Seq ID No. 5 – 10. ‘325 does not teach the method of administering the CD27 antibody and transferring autogenic or allogenic T cells to a subject. Claims 6-7 of the ‘325 further limit claim 1 to a composition comprising said antibody and adjuvant.
Lotze teaches a method of treating a cancer with a population of TILs comprising the steps of administering a therapeutically effective portion of the TILs to a patient with cancer, and further treating the patient with a TNFRSF agonist, wherein the TILS are obtained from a tumor of a patient (Paragraph [0031], section (a) and (f)) (interpreted as transferring autogenic T cells to the subject). Lotze teaches that the CD27 agonist is varlimumab (Paragraph [0022], section (f)) (interpreted as administering a CD27 antibody to the subject).
It would have been obvious for one of ordinary skill in the art to, before the effective filing date of the claimed invention, to have used the specific human CD27 antibody, as taught by ‘325, in the method of treating a cancer as taught by Lotze, in order to provide the sequences of the CD27 antibody for use.
Response to Applicants’ Arguments as they apply to Double Patenting Rejection
At page 7 of the remarks filed on 8 September 2025, Applicants offer to provide a terminal disclaimer upon indication by the Examiner of allowable claims. However, Applicant’s request is not a proper response to the rejections of record as it neither traverses the grounds of rejection by providing specific arguments, nor indicates that a terminal disclaimer has been filed to overcome the rejection. As such, the rejections of record stand.
Claim Rejection - 35 USC § 112(b)
The rejection of claims 1, 6, 7, 14, 17 – 19, 21, and 25 is maintained 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 1 is indefinite for the recitation of “method of increasing the survival and expansion of T cells transferred during ACT” in lines 1 – 2. It is unclear how the body of the claim, wherein a CD27 antibody is administered, and T cells are transferred to the subject” is a method of increasing the survival and expansion of T cells transferred during ACT. Thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of “method of increasing the survival and expansion of T cells transferred during ACT” in lines 1-2. “Increase” is relative terms that renders the claim indefinite. The term “increase” is not defined by the claim and the Specification does not provide a standard for ascertaining the requisite amount of increase of the survival of the T cells transferred during the ACT, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention and, thus, the metes and bounds of the claim cannot be determined.
Claim 6, 7, 14, 17 – 19, 21, and 25 are indefinite insofar as they ultimately depend from claim 1.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 6, 7, 14, 17 – 19, and 25 is maintained under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated by Lotze et al. (hereinafter referred to as “Lotze”) (WO2018129332, published 12 July, 2018).
Regarding claim 1, Lotze teaches a method of treating a cancer with a population of TILs comprising the steps of administering a therapeutically effective portion of the TILs to a patient with cancer, and further treating the patient with a TNFRSF agonist, wherein the TILS are obtained from a tumor of a patient (Paragraph [0031], section (a) and (f)) ( interpreted as transferring autogenic T cells to the subject). Lotze teaches that the CD27 agonist is varlimumab (Paragraph [0022], section (f)) (interpreted as administering a CD27 antibody to the subject) (Please Note: the as-Filed Specification teaches that the CD27 antibody is varlimumab (Paragraph [0009]). Lotze teaches that the TNFRSF agonist is administered prior to the step of resecting of a tumor and prior to the administering of the TILs to the patient (Paragraph [00143] “the population of TILs and/or the pharmaceutical composition is for use in treating cancer in combination with a TNFRSF agonist wherein the TNFRSF agonist is for administration prior to the step of resecting of a tumor from the patient” and [00145]) (interpreted as the CD27 antibody is administered before the T cells are transferred).
Regarding claim 6, Lotze teaches that the TILS (T cells) are obtained from a tumor, expanded using a TNFRSF agonist, and then introduced into the subject (Paragraph [0014]) (interpreted as the autogenic cells). Lotze teaches that the TNFRSF agonists (i.e. CD27 agonist) can be use
Regarding claim 7, Lotze teaches that the TNFRSF agonists (i.e. CD27 agonist) can be used to expand T cells transduced with a CAR – T cell (Paragraph [001075]).
Regarding claim 14, Lotze teaches that the CD27 agonist is varlimumab (Paragraph [0022], section (f)) (interpreted as the CD27 antibody able to block the CD70-CD27 interaction). (Please Note: The as-Filed Specification teaches that varlilumab is able to block the binding of human CD27 with human and mouse CD70).
Regarding claim 17Lotze teaches the monoclonal antibody varlilumab, wherein seq ID No. 133 is the heavy chain CDR1, Seq ID No. 134 is the heavy chain CDR2, and Seq ID NO. 135 is the heavy chain CDR3 (Paragraphs [00349] – [00351]). Seq ID Nos 133 – 135 have a 100% alignment score with instant Seq ID No. 5 – 7. Further, Lotze teaches that seq ID No. 136 is the light chain CDR1, Seq ID No. 137 is the light chain CDR2, and Seq ID NO. 138 is the light chain CDR3 (Paragraphs [00352] – [00354]). Seq ID Nos 136 - 138 have a 100% alignment score with instant Seq ID No. 8 - 10
Please see alignment of Seq ID No. 133 to Seq ID No. 5:
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Regarding claim 18, Lotze teaches that Seq ID No. 129 is the heavy chain, and Seq ID No. 130 for the CD27 agonist monoclonal antibody varlilumab (Paragraph [00345] and [00346]). Seq ID No. 129 and 130 have a 100% alignment score with instant Seq ID No. 3 and 4.
Please see alignment of Seq ID No. 129 to instant Seq ID No. 3:
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Regarding claim 19, Lotze teaches that the CD27 agonist is varlimumab (Paragraph [0022], section (f)).
Regarding claim 21, Lotze teaches that the TNFRSF agonist is administered prior to the step of resecting of a tumor and prior to the administering of the TILs to the patient (Paragraph [00143] and [00145]) (interpreted as the CD27 antibody is administered before the T cells are transferred).
Lotze teaches that the initial expansion of the first population of TILs to obtain a second population, wherein the first cell culture medium comprises IL-2 and a TNFRSF agonist, occurs over a period of 21 days (Paragraph [0023]). Then, the rapid expansion of the second population to the third population, wherein the second culture medium comprises IL-2, OKT-3, PBMCs, and the TNFRSF agonist, is performed over a period of 14 day of less (Paragraph [0023]). This is interpreted as CD27 antibody is administered at least 12 hours before the T cells are transferred).
Regarding claim 25, Lotze teaches that the T cells are administered by intravenous infusion (Paragraph [001127]).
Lotze meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Response to Arguments as they apply to rejection of claims 1, 6, 7, 14, 17 – 19, and 25 under 35 USC § 102
Applicant’s arguments filed 8 September, 2025 have been fully considered but they are not persuasive. Applicant essentially asserts (a) the regulatory T cells of the patient are reduced before administering the cell graft in order to promote the survival and expansion of the exogenously transferred T cells (Applicant Remarks, pg. 8, third paragraph); (b) Lotze fails to teach administering the CD27 antibody to the subject before the ACT, as claimed (Applicant Remarks, pg. 8, fourth paragraph); and (c) Lotze fails to teach the mutated human CD27 comprising the R87A mutation (Seq. 71), as taught in claim 9.
Regarding (a), Applicant’s arguments are not found persuasive. MPEP 2111.02 teaches
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020).
In the instant case, the body of claim 1 (the independent claim) sets forth all the limitation of claimed invention, and the preamble only recites the purpose of the invention (i.e. a method of increasing survival and expansion of T cells transferred during ACT). Thus, the preamble is not considered a limitation. In other words, Lotze teaches all the limitations of the claimed invention, and thus, will also inherently teach that method of increasing survival and expansion of the T cells transferred during the ACT. Further, the instantly recited claims do not recite and/or teach reducing the regulatory T cells before administering the graft.
Regarding (b), Applicant’s argument that Lotze fails to teach administering the CD27 antibody to the subject before the ACT is not found persuasive. Lotze teaches that the TNFRSF agonist (the CD27 agonist - varlimumab) can be administered on the day after the administration of the TILs (Paragraph [0142]) or is administered prior to the step of resecting of a tumor from the patient (Paragraph [0143]). (Please note: the as-Filed Specification teaches that the CD27 antibody is varlimumab (Paragraph [0009]). As noted above, the TILs are resected from the tumor, resected, and then introduced into the subject (Paragraph [0014]). Thus, Lotze teaches does teach that the CD27 agonist is administered before the TILs.
Regarding (C), Applicant is reminded of the restriction required between claim 7 and 8. In the response to restriction filed 20 February, 2025, Applicant elected claim 7, and thus claim 8 was withdrawn. As noted above, claim 9 refers to back to withdrawn claim 8 and, therefore, claim 9 was not been examined on the merits.
Thus, the rejection is maintained for the reasons of record.
Conclusion
Claims 1, 6, 7, 14, 17 – 19, 21, and 25remain rejected.
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 extension fee 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 VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634