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 .
DETAILED ACTION
Claim status
Claims 1, 6-9, 13-20, and 27-29 are pending
Claims 6-9, 13-16, 18-20 are withdrawn
Claims 1, 17, 27-29 are under examination
Election/Restrictions
Applicant’s election of the following invention in the reply filed on 12/04/2025 is acknowledged.
Applicant's election with traverse is acknowledged. The traversal is on the ground(s) that there would be no serious search burden to examine multiple groups.
This is not found persuasive because examiner was able to provide art which satisfied the limitations of the cell-based product claims without being able to satisfy the limitations of all the nucleic acid-based product claims and/or method claims thereby demonstrating that a search burden exists between the restricted groups (US 111a restriction practice, where the product was alleged to be distinct because it could be used in a different method).
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1, 17, 27-29, drawn to a CAR T cell or CAR NK cell.
Claims 6-9, 13-16, 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of species has been omitted. It appears that the species election of T cells or NK cells has been inadvertently omitted based on the bona fide response to elect a single group of inventions for prosecution (i.e., Group I).
Nevertheless, the closest prior art fully encompasses T cells and NK cells, and therefore the Examiner has withdrawn the species election between T cell and NK cells.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/09/2023, 5/03/2023, 8/13/2024, and 7/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objection to Drawings
Sequence Compliance
Figures 15-17, 26, and 30B of the Specification do not conform to sequence rules, requiring the use of “SEQ ID NO:” (37 CFR 1.821-1.825).
Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. 37 CFR 1.821 (d).
The applicant is reminded that the specification must be amended in order to comply with regulations cited above. All references to sequences in claims and specification should be referred to as “SEQ ID NO:1”, for example. To avoid all doubts of the examiner and to ensure correct interpretation of the claims and specification, the identification of sequences with proper sequence identifiers is required.
Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Objection to Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other form of browser-executable code (p. 20, lines 10-14, p. 38, line 25). Applicant is required to amend or delete the embedded hyperlink and/or other form of browser-executable code. For example, “www” can be replaced with “world wide web” as the URL code, and/or remove the “http” header. See MPEP § 608.01.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 17, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Valdes et al., (US2015/0023937, filed 7/18/2014, with priority to 61/847,957 filed 7/18/2013, see IDS filed 3/09/2023) in view of Bae et al., (Clin Cancer Res, 2005, 11:1629-1638), see IDS filed 3/09/2023
In regard to claims 1 and 27, Valdes teaches genetically modified immune cells such as T cells and NK cells that express chimeric antigen receptors (CARs) (Abstract, [0011] of 2015/0023937, see also of [0018, 0021] of 61/847,957). Specifically, Valdes teaches the modified immune cells comprise at least a first and second CAR that target at least two antigens ([0022] of 2015/0023937, see also of [0018] of 61/847,957).
In regard to the CARs, Valdes teaches each CAR comprises (i) an antigen binding domain, (ii) a spacer (alias hinge), (iii) a transmembrane domain, and (iv) an endodomain comprising activation and co-stimulatory domains ([0062-0069] of 2015/0023937, see also of [0064-0068] of 61/847,957). In regard to the antigen binding domains, Valdes teaches the antigen binding domains of CD19 and CD20 ([0069] of 2015/0023937, see also of [0068] of 61/847,957).
In regard to claim 17, Valdes teaches the immune cells are in a pharmaceutical composition [0090, 0129-0130] of 61/847,957.
However, Valdes is silent with respect to preferred embodiment of an immune cell genetically modified to comprise a first CAR that binds CD19, and second CAR that binds CD20.
Nevertheless, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to prepare a T cell or NK cell comprising CD19 and CD20 CARs because each of the individual elements of the instant claims are independently presented by Valdes as embodiments and are taught that they can be combined in various embodiments; therefore a combination of all the elements into a single embodiment would be apparent to an artisan skilled in CAR immunotherapy in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)). Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of filing of the invention. For examples, Bae et al., (2005) teaches that combining a CD19 CAR and a CD20 CAR in an immune cell would have been especially advantageous because this would have specifically target malignant B cells that have undergone neoplastic transformation including leukemia and lymphoma (p. 1635, 2nd para.). Thus, each of the elements (T cells and NK cells comprising a first and second CAR, CD19 CARs, CD20 CARs, transduction methods and formulations) are taught by Valdes and further they are taught in various combinations and are shown to be used in a method for producing genetically modified CAR immune cells. It would be therefore predictably obvious to use a combination of these elements in said T cell or NK cell composition.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Valdes et al., (US2015/0023937, filed 7/18/2014, with priority to 61/847,957 filed 7/18/2013), in view of Bae et al., (Clin Cancer Res, 2005, 11:1629-1638), as applied to claim 1, in further view of Junghans et al., (WO2010/085660, filed 1/22/2010, now US Patent 9,206,440, see IDS filed 3/09/2023)
As stated supra, Valdes et al. suggest a genetically modified immune cell such as a T cell or NK cell which co-express a first CAR that binds CD19 and a second CAR that binds CD20.
In regard to claims 28 and 29, as per the product-by-process limitation of transducing a T cell or NK cells from a blood sample ex vivo. Valdes teaches the cells to be genetically modified are from a subject’s peripheral blood (([0137, 0139] of 2015/0023937, see also of [0136, 0138] of 61/847,957), and that the genetic modification step occurs ex vivo ([0142-0143] of 2015/0023937, see also of [0141-0142] of 61/847,957). Finally, Valdes suggest the first and second CAR being encoded from the same expression construct ([0023] of 2015/0023937, see also of [0010] of 61/847,957).
However, Valdes is silent to a preferred embodiment of a single nucleic acid encoding a first and second CAR.
In regard to claims 28 and 29, Junghans teaches genetically modified immune cells that express chimeric immune receptors (CAR) (p. 3, 2nd para. p. 23, last para., p. 25, 1st para., p. 39, 1st para., p. 76, 1st para. see Figs. 28, 35 & 36). Specifically, Junghans teaches the first CAR and second CAR are encoded by the same nucleic acid separated by an IRES (Figs. 7-11, 33, 36-38, 40, 43, see excerpt from Fig. 36 below).
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Accordingly, it would have been obvious to one of ordinary skill in the art at the time of filing to ex vivo prepare the peripheral blood T cells or NK cells comprising a first and second CAR as taught by Valdes, and combine more than two CARs into a single nucleic acid as taught by Junghans with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, as state supra, Valdes suggests that multiple CARs can be expressed in a single nucleic acid. Moreover, Junghans teaches that it would have been obvious to do so in order to ensure that the immune cells exhibit high coexpression of the CARs (p. 77-78, see Fig. 36). Finally, Applicant is reminded that even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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