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 .
Claims Status
The Amendment filed on 21Jan2026 is acknowledged in which claim(s) 2-4, 6, 8-45, and 47 were canceled by Applicant.
Claim(s) 1, 5, 7, 46, and 48-50 is/are currently pending and presented for examination on the merits.
Formal Matters
The Amendment filed on 21Jan2026 indicates claims 48-50 are “Original”, however these claims were previously amended. Additionally, claim 49 has been amended to “CD10+” rather than “CD19+” (without required markings for amendments), relative to the previous Amendment filed on 02Jun2022.
Response to Amendment and Arguments
All previous rejections and/or objections of claim(s) 2, 6, 8-9, and 23-31 are moot in view of claim cancelation.
The objection(s) to the drawings have been withdrawn in view of the Amendment filed on 21Jan2026.
The rejection(s) of claim(s) 1, 5, 7, 46, and 48-50 under 35 U.S.C. § 102 have been withdrawn in view of the recent claim amendment filed on 21Jan2026, which added new limitations to the claims, that were not considered in the previous rejections.
The previously presented objection(s) to the specification is/are maintained for reasons provided below. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance. Only Applicant arguments pertaining to maintained and/or new rejection(s)/objection(s) are addressed herein.
Maintained Objections
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., Miltenyi, Invitrogen, Dynabeads, UPENN, SignaGen, vector builder), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Response to Arguments
Applicant did not submit a substitute specification or supply arguments regarding the previous objection to the specification.
In response, the objection to the specification is maintained for lack of response from Applicant.
New Rejections/Objections Necessitated by Amendment
Claim Objections
Claim(s) 7 is/are objected to because of the following informalities:
There is an internal period in line 6. Each claim must begin with a capital letter and end with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995); MPEP 608.01(m).
Line 7 recites “(b)” and line 11 recites “(c)” but there is no “(a)”. There should be an “(a)” in line 2 before “the subpopulation”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim(s) 1, 5, 7, 46, and 48-50 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 (and dependent claims 5, 7, 46, 48-50) recites the limitation "…(c) has a greater percentage of cells expressing CD127 than a population of peripheral blood mononuclear cell T cells that also express said CAR; (d) has a lower percentage of cells expressing CD127 than a population of peripheral blood mononuclear cell T cells that also express said CAR…", and claim 1(i)(a)-(g) are joined by an “and”, rendering the claim indefinite. It is unclear if the instant invention requires a greater or a lower percentage of CD127 expression in the placental perfusate CAR T cell population relative to PBMC CAR T cells. For the purposes of compact prosecution, the phrase recited above is considered to mean any amount (higher or lower) of CD127 expression in the placental perfusate CAR T cells relative to the PBMC derived CAR T cells. This rejection may be overcome by amending claim 1 to clearly recite the limitations of the instant invention. Dependent claims 5, 7, 46, and 48 can overcome this rejection by amending claim 1 as described above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 5, 7, 46, and 48-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Karasiewicz et al. (Blood, 13 November 2019 (2019-11-13), XP055669637; hereinafter “Karasiewicz”), as evidenced by and BD Biosciences (BD Biosciences, CD Marker Handbook, 2016; hereinafter “BD”), in view of WO 2015/073800 A2 (hereinafter “WO800”), as evidenced by the instant disclosure.
Regarding claim 1, Karasiewicz teaches allogeneic placenta-derived T cells (P-T) are genetically modified by retroviral transduction to express a CD19 CAR [e.g., pg. 1 para 1; pg. 2, para 1].
Regarding claim 5, 7, Karasiewicz further teaches that, unlike PBMCs, placental derived T cells (P-T cells) are mostly naïve (CD45RA+) and can be readily expanded while maintaining a greater expression of naïve/memory markers and a lower expression of effector/exhaustion markers [e.g., pg. 1, para 1].
Regarding claims 46, 48-50, Karasiewicz further teaches allogeneic placental CD19 CAR T cells for the treatment of B cell malignancies [e.g., pg. 1, para 1]. Karasiewicz teaches functional activity of the placental CD19 CAR T against CD19+ Burkitt’s Lymphoma and Acute Lymphoblastic Leukemia [e.g., pg. 2, para 2]. Human B cells are well-known in the art to express CD10, as evidenced by BD [e.g., pg. 3].
Karasiewicz does not expressly teach (I) allogeneic CD19 direct CAR placenta perfusate T cells (hereinafter placenta perfusate T cells will be referred to as “PT” cells) wherein (1) the PT cells express CD127, have a greater percentage of cells expressing CD27, CCR7, CD62L and have a lower percentage of cells expressing Tim-3 than PBMCs that express the same CAR, and have Teff, CD8+, Tcm, Tscm/naïve and CD4+ T populations; wherein (a) the Tscm/naïve subpopulation comprises greater than about 30%, about 40%, about 45%, or about 50% of the total CAR+ PT population, (b) the Teff comprises less than about 75%, about 70%, about 60%, about 50%, about 40%, about 35% or about 30% of the total CAR+ PT population, the Tcm subpopulation comprises less than about 10%, about 8%, about 6%, about 5%, about 4%, or about 3% of the total CAR+ PT population, and the CD8+ subpopulation comprises greater than about 50%, about 60%, about 80%, about 90%, or about 100% of the relative abundance of CD4+ populations; or (II) a method of treating cancer or a symptom thereof in a subject in need thereof comprising administering an effective amount of the CAR+ PT cells of “(I)” above wherein (1) the cancer is a CD10+ B cell cancer, or (2) the PT cells are allogeneic.
Regarding claims 1, 5, 7, 46, 48-50, WO800 teaches human placental perfusate T cells are suitable for allogeneic therapy [e.g., ¶ 00166]. As evidenced by the instant specification [e.g., examples 1-2; “summary”], the instant claimed specific CAR+ PT cells CD marker(s) expression relative to PBMCs as well as specific subpopulation compositions were not engineered but rather were observed, and therefore are considered naturally occurring.
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the general “placenta-derived T cells” of the CD19 directed placenta-derived T cells as taught by Karasiewicz, with the placental perfusate T cells taught by WO800, to arrive at CD19 directed placental perfusate CAR T cells. A PHOSITA would have been motivated to substitute the placenta-derived T cells in the CD19 directed placenta-derived CAR T cells as taught by Karasiewicz, with the placental perfusate T cells taught by WO800, because Karasiewicz teaches a generic “placenta-derived” T cell for allogeneic CAR T cell therapy, and WO800 teaches that the characterization of human placental perfusate cells indicated particular suitability for allogeneic therapies (e.g., as in Karasiewicz). There would have been a reasonable expectation of success for a PHOSITA to substitute the general “placenta-derived T cells” of the CD19 directed placenta-derived CAR T cells as taught by Karasiewicz, with the specific placental perfusate T cells taught by WO800, because Karasiewicz teaches allogeneic placenta derived CAR T cells, and WO800 teaches placental perfusate cells (e.g., a specific type of placenta-derived T cells) are particularly suited for allogeneic therapy. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified CD19 directed placental perfusate CAR T cells of Karasiewicz and WO800 (see above) to include that (1) the PT cells express CD127, have a greater percentage of cells expressing CD27, CCR7, CD62L and have a lower percentage of cells expressing Tim-3 than PBMCs that express the same CAR, and have Teff, CD8+, Tcm, Tscm/naïve and CD4+ T populations; wherein (a) the Tscm/naïve subpopulation comprises greater than about 30%, about 40%, about 45%, or about 50% of the total CAR+ PT population, (b) the Teff comprises less than about 75%, about 70%, about 60%, about 50%, about 40%, about 35%, or about 30% of the total CAR+ PT population, the Tcm subpopulation comprises less than about 10%, about 8%, about 6%, about 5%, about 4%, or about 3% of the total CAR+ PT population, and the CD8+ subpopulation comprises greater than about 50%, about 60%, about 80%, about 90%, or about 100% of the relative abundance of CD4+ populations; and (2) a method of treating cancer or a symptom thereof in a subject in need thereof comprising administering an effective amount of the CD19 directed CAR PT cells (see above) wherein (1) the cancer is a CD10+ B cell cancer, and/or (2) the PT cells are allogeneic, as taught by Karasiewicz and/or WO800 as evidenced by BD or the instant disclosure, because Karasiewicz and WO800 teach the modified CD19 directed placental perfusate CAR T cells, Karasiewicz teaches allogeneic CD19 directed placenta derived CAR T cells as an effect therapy for CD19+ B cell cancers, the placental perfusate cell characterizations listed above (e.g., CD marker expression relative to PBMCs, subpopulations) are naturally occurring (e.g., observed characterizations, not engineered) in placental perfusate cells (see above), and CD10 expression is known in the art to naturally occur across B cells (see above). There is an expectation of success for a PHOPSITA to include the above-listed methods of treating as taught by karasiewicz, and specific naturally occurring characteristics of placental perfusate T cells or B cells, because Karasiewicz and WO800 teach the base composition of an allogeneic CD19 directed placental perfusate CAR T cell, Karasiewicz teaches allogeneic CD19 directed placenta derived CAR T cells are effective in treating CD19+ B cell cancers, and the specific placental perfusate (e.g., a specific type of placenta-derived cell) T cells and/or B cell characterizations (e.g., CD marker expression) are considered naturally occurring (see above). This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues that Karasiewicz does not teach the limitations of amended claim 1, and further that Karasiewicz does not teach placental perfusate derived T cells [e.g., Remarks pgs. 1-3].
In response, the new limitations of amended claim 1 are addressed in the new rejections above. Briefly, Karasiewicz was relied upon to teach allogeneic CD19 directed placenta derived CAR T cells for B cell cancer therapy, and new reference WO800 was relied upon to teach placental perfusate CAR T cells were particularly suited for allogeneic cell therapies, and BD and the instant specification served as evidentiary references with respects to naturally occurring limitations (see rejection above for details). Applicant argument has been fully considered and is not found persuasive.
Conclusion
No claims are currently allowed.
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 AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643