DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received July 8, 2026 are acknowledged.
Claim 27 is canceled.
Claims 5, 9, and 24 have been amended.
Claims 1-26 and 28-30 are pending in the instant application.
Applicant’s election without traverse of the invention of group I, drawn to cells expressing anti-CD19 CAR in the reply filed on July 8, 2026 is acknowledged.
Claims 15-21 and 28-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 8, 2026.
Claims 1-14 and 22-26 are under examination in this office action as they read upon cells expressing anti-CD19 CAR constructs
Information Disclosure Statement
The IDS form received 6/9/2023 is acknowledged and the references cited therein have been considered.
The listing of references in the specification on page 62-63 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.
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 1-13 and 22-26 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.
Regarding claim 1, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Specifically, are the subranges 7-12 and 7-10 as well as the exact number 8 that appear after “such as” in the independent claim actual limitations that must be met or just examples of things lying within the range of “7 to 14 amino acids”? Note also that in addition to the “such as” exemplification, in US practice reciting a range within a range in the same claim (such as the broadest range 7-14 and the narrower subrange 7-10) is generally not permitted as it also raises questions of indefiniteness concerning what is exemplification and what is the actual limitation recited by the claim.
Claim 4 also recites “such as” prior to a list of linker sequences which ends with one in particular being “preferably” identified. Does the claimed product actually have to comprise one of the recited linker sequences or are they just a list of things the linker “could be” rather than what it must be. See again MPEP § 2173.05(d).
Claims 24 was amended to remove “preferable” language yet recites two occurrences of “such as” and thus the claim is indefinite as it is unclear if applicant intends non-limiting examples or actual required limitations. Additionally, claim 24 recites “the cell according to claim 23, wherein the chimeric Caspase-9 polypeptide comprises” yet neither claim 23 nor any claim in the chain of dependency discuss Caspase 9. As such the term “Caspase 9” lacks any antecedent basis in the claims.
Claim 25 is indefinite for to the recitation of “and/or” such that while it is clear that cell expansion is to occur in the presence of both IL-7 and IL-15 it is unclear if IL-7 and IL-15 are also necessarily present during activation and during transduction. Language appropriate to clarify when IL-7 and UL-15 is necessarily present is required.
It is noted that all claims either directly or indirectly depend from independent claim, 1, and none of the dependent claims apart from claim 14 appear to resolve the issue discussed above concerning claim 1. As such all claims apart from claim 14 are appropriately joined to this rejection.
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 1-5, 9-11, 22, 23, 25 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fry et al. (US 2018/0111992).
Fry et al. teach chimeric antigen receptors that bind CD19, as well as cells expressing such receptors and their use in treating human cancers (see entire document, particularly the title, abstract, and claims). Notably, such anti-CD19 Car are disclosed as comprising a hinge, transmembrane, costimulatory and CD3zeta chain domains (see for example paragraph [0004] and Figure 5) and comprising a single chain Fv derived from the FMC63 antibody (see for example paragraphs [0024-0026] and note that instant VL of SEQ ID NO:15 is SEQ ID NO:16 of Fry while instant VH SEQ ID NO:16 is SEQ IDZ NO:15 of Fry, see enclosed sequence alignments). Additionally, a variety of linkers are disclosed as being used in connecting the VH and VL sequences, including linkers of exactly 8 amino acids in length as well as comprising glycine-serine rich linkers of the formula [GGGGS]n, wherein n=2 (see for example paragraphs [0029-0034], and the CAR constructs are disclosed as having leader sequences needed for proper orientation of the expressed transmembrane protein (see for example paragraph [0035]). The CAR of Fry et al. are disclosed as comprising hinge region 100% identical to instant SEQ ID NO:21 (see enclosed alignment of instant SEQ ID NO:21 to SEQ ID NO:33 of Fry et al. as well as paragraph [0036] of Fry et al.) as well as a transmembrane domain comprising instant SEQ ID NO:28 (see particularly paragraph [0026] as well as the enclosed alignment of instant SEQ ID NO:28 to SEQ ID NO:26 of Fry et al.). Additionally, Fry et al. disclose their constructs comprise a CD137/4-1BB domain that is identical to instant SEQ ID NO:30 (see particularly paragraph [0038] as well as the alignment of instant SEQ ID NO:30 to SEQ ID NO:27 of Fry et al.) and a CD3zeta domain identical to instant SEQ ID NO:32 (see particularly paragraph [0039] and the enclosed alignment of instant SEQ ID NO:32 to SEQ ID NO28 of Fry et al.). Such constructs are disclosed as being expressed on T cells (see for example paragraphs [0069-0070] and such cells are disclosed as being transduced with lentiviral expression vectors and then administered as part of pharmaceutical compositions (see for example paragraphs [0073-0076] and examples 3 and 4). Notably expression vectors comprising inducible suicide genes including HSV thymidine kinase are disclosed (see particularly paragraph [0067]). Therefore the prior art anticipates the instant claimed invention.
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.
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 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Fry et al. (US 2018/0111992) in view of Pule et al. (WO 2013/153391).
The teachings of Fry et al have been discussed above, and while their CAR constructs are disclosed as comprising domains from CD8, such domains are not disclosed as further having the minimal CD34 epitope of instant SEQ ID NO:25 attached thereto as a detectable marker.
Pule et al. disclose a minimal epitope of CD34 which is to be used in antibody based methods of selecting cells transduced with CAR constructs prior to cell administration wherein the epitope is attached to the CD8 stalk (see entire document, particularly the abstract, claims, pages 6-7, Figure 10). Notably, the minimal CD34 epitope is called “QBEndlO-binding epitope” and is identical in to sequence as instant SEQ ID NO:25 (see enclose sequence alignment).
Therefore, it would have been obvious to ordinary artisans to add a CD34 tag to the CAR constructs so that cells successfully transduced and expressing the desired CAR could be readily purified from bulk cells prior to administration to the patient as disclosed by Pule et al.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Fry et al. (US 2018/0111992) in view of Konto et al. (US 2019/0125799).
The teachings of Fry et al have been discussed above, and while their CAR constructs are disclosed as comprising domains from CD8, the specific sequence of instant SEQ ID NO:40 is not explicitly disclosed as being present.
Konto et al. disclose anti-CD19 CAR constructs which comprise CD8 domains which comprise the polypeptide sequence of instant SEQ ID NO:40 (see entire document, particularly the abstract, claims and enclosed sequence alignments).
Therefore it would be obvious to artisans that the CD8 domains of Konto et al. could be used in the expression of the CAR constructs of Fry et al. as both groups successfully expressed anti-CD19 CAR constructs that demonstrated killing efficacy both in vitro and in vivo. Notably, both groups disclose using domains from CD8 as part of their CAR constructs and applicant is remined that as per MPEP 2144.06, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Fry et al. (US 2018/0111992) in view of WO 2017/068361.
The teachings of Fry et al have been discussed above, and while their CAR constructs are disclosed as comprising a signal peptide (and indeed require one so that the mature transmembrane protein is expressed in its proper orientation in the plasma membrane) the signal peptide of SEQ ID NO:41 is not disclosed.
The ‘361 document disclose the successful expression of CAR constructs comprising a signal peptide identical to SEQ ID NO:41 (see entire document, particularly the abstract, claims and enclosed sequence alignments).
Therefore it would be obvious to artisans that the signal peptide of the ‘361 document could be used in the expression of the CAR constructs of Fry et al. with more than a reasonable expectation of success as both groups successfully expressed CAR constructs and note that signal peptides by definition are absent in the mature CAR construct expressed on the surface of a cell. Applicant is further reminded that as per MPEP 2144.06, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Fry et al. (US 2018/0111992) in view of Spencer et al. (WO 2015/134877).
The teachings of Fry et al have been discussed above, and while cells comprising their CAR constructs are disclosed as comprising suicide genes, such genes are not disclosed as comprising caspase 9 joined to FKBP12.
Spencer et al. disclose suicide genes that are to be contrasfected with therapeutic constructs such as CARs in order to provide a way to kill the transfected cells in the event of graft versus host disease or other undesired complications arising from the presence of the transfected cells in the patient (see entire document, particularly the abstract and claims). Notably, such suicide genes are disclosed as comprising FKBP12V36 fused to caspase 9 and a cleavable 2A polypeptide sequence (see particularly pages 2-8, 38-41, 47, and 48).
Therefore it would be obvious to artisans that the suicide genes of Spencer et al could be added to the CAR cells of Fry et al. Artisans would be motivated to do so in order to have a way to remove the administered CAR cells from the patient in case unwanted consequences, such as but not limited to GvHD are observed in the treated patient.
Claim Objections
Claim 11 is objected to as it comprises an obvious typographical error. Specifically, the claim recites a polypeptide sequence accompanied by a SEQ ID number and the polypeptide sequence ends in the symbol “*” which is not an amino acid. Removal of the extra erroneous “*” from the end of the sequence in the claim is required.
Claim 14 is objected to as being dependent upon a rejected independent claim, but would be allowable if rewritten in independent form including all of the limitations of the independent claim and any intervening claims.
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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, Misook Yu can be reached at 571-272-0839. 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.
Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
Prosecution Insights