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 .
Election/Restrictions
Applicant's reply to the Restriction Requirement, dated October 7, 2025, has been received. By way of this reply, Applicant has elected the species of CD33 as the species of lineage-specific cell-surface protein, bone marrow cells as the species of hematopoietic cells, allogeneic cells; leukemia as the species of cancer, and base editing genetic modifications as the species of genetic modification.
Applicant’s election of species above in the reply filed on October 7, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-3, 8-11, 16-17, 22-23, 26-28, 34-36, and 61-63 are pending in the application. Claim 27 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 7, 2025.
Claims 1-3, 8-11, 16-17, 22-23, 26, 28, 34-36, and 61-63 are therefore under examination before the Office.
Priority
Claims 62 and 63 are drawn to base editing and the use of an adenine base editor. The earliest support for these claims in the specification is found in the PCT document PCT/US18/20327 with a priority dated of February 28, 2018, at page 45. Accordingly, claims 62 and 63 have a priority date of February 28, 2018.
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, 8-11, 16-17, 22-23, 26, 28, 34-36, and 61-63 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.
The claims are drawn to methods of using genetically engineered hematopoietic cells lacking a non-essential epitope. However, the metes and bounds of what constitutes a "non-essential epitope" are not clear.
Applicant's definition of a "non-essential epitope" only refers to the epitope's properties, and broadly encompass both substitution and deletion mutations (see Specification at pages 16-17). Under the broadest reasonable interpretation of non-essential, as defined in the specification, almost every amino acid would be essential, since it would contribute to the function and/or the conformation of the protein.
Applicant's specification does not define the boundaries of the epitope, nor its size or any other readily quantitative characteristic of the epitope. The skilled artisan would not be appraised of exactly what this non-essential epitope is meant to include. For these reasons, the claims are indefinite.
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.
Claim Rejections - 35 USC § 102
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, 8, 10-11, 16-17, 22, 28, 34-36 and 61 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Lutteropp (US20160144026A1, cited in IDS as U.S. patent 10,201,606).
Lutteropp teaches a combination immunotherapy, comprising an antigen-recognizing receptor, which recognizes an antigen present on target cells, and hematopoietic cells resistant to recognition of said antigen by said antigen-recognizing receptor (para. 0015 and claim 1).
Lutteropp further teaches that the receptor may bind CD19 (para. 0044 and 0059). According to Applicant's specification at page 5 and claim 22, CD19 is a lineage-specific protein.
Lutteropp further teaches that the hematopoietic cells have an altered epitope that does not alter or affect the natural function of said antigen on the cells (i.e., lacking a non-essential epitope, see Applicant's specification at page 16).
Lutteropp further teaches mutations in CD20 that abrogate CD20 recognition by the antigen recognizing receptor (para. 0117), which is pertinent to claim 2.
Lutteropp further teaches that the antigen binding receptor may be an scFv (para. 0097), which is pertinent to claim 8.
Lutteropp further teaches that the antigen binding receptor may be a chimeric antigen receptor (CAR) expressed on a T cell (para. 0038), which is pertinent to claims 10 and 11.
Lutteropp further teaches that the modified antigen contains three or more amino acid deletions (para. 0077), which is pertinent to claims 16 and 17.
Lutteropp further teaches that the hematopoietic cells may be allogeneic (para. 0056 and claim 9), which is pertinent to claim 28.
Lutteropp further teaches that the subject to which the cells are administered to has lymphoid leukemia (para. 0055), which is pertinent to claims 34-36.
Lutteropp further teaches that the hematopoietic cells may be genetically modified by zinc finger nucleases (ZFN), transcription activator-like effector-based nucleases (TALEN), or CRISPR (para. 0054), which is pertinent to claim 61.
Claims 1, 3, 8-11, 22-23, 26, 28, 34-36, and 61 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Mukherjee (US20170326179A1, cited in IDS as U.S. patent 10,137,155).
Mukherjee teaches methods for treating a hematopoietic malignancy, the method comprising administering to a subject in need thereof an effective amount of an agent targeting a lineage-specific cell-surface antigen, wherein the agent comprises an antigen-binding fragment that binds the lineage-specific cell-specific cell-surface antigen, and hematopoietic cells that are deficient in the lineage-specific cell-surface antigens (para. 0007-0008). Under the broadest reasonable interpretation of the claims, a complete deletion of the target antigen would also naturally include the cell lacking the non-essential epitope to which the cytotoxic agent binds.
Mukherjee further teaches that the agent may comprise an scFv (para. 0062), which is pertinent to claim 8.
Mukherjee further teaches that the agent may comprise an antibody-drug conjugate (para. 0125), which is pertinent to claim 9.
Mukherjee further teaches that the agent can be an immune cell (e.g., a T cell) expressing a chimeric receptor that comprises the antigen-binding fragment that binds the lineage-specific cell-surface antigen (para. 0008), which is pertinent to claims 10 and 11.
Mukherjee further teaches that the antigen is CD33 (para. 0009-0010), which is pertinent to claims 22 and 23.
Mukherjee further teaches that the hematopoietic stem cells may be isolated from bone marrow or peripheral blood mononuclear cells (PBMCs) (para. 0008), which is pertinent to claims 26 and 28.
Mukherjee further teaches that the subject may have leukemia or acute lymphoblastic leukemia (para. 0014), which is pertinent to claims 34-36.
Mukherjee further teaches that the hematopoietic cells may be genetically modified by zinc finger nucleases (ZFN), transcription activator-like effector-based nucleases (TALEN), or CRISPR (para. 0017), which is pertinent to claim 61.
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, 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.
Claims 62 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Lutteropp as applied to claim 61 above, and further in view of Gaudelli (Nature, 2017 Nov 23;551(7681):464-471).
The teachings of Lutteropp have been discussed supra. However, Lutteropp does not teach an adenine base editor.
Gaudelli teaches adenine base editors (ABEs) that mediate the conversion of A•T to G•C in genomic DNA in the context of a CRISPR system with hide fidelity (abstract).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Lutteropp and Gaudelli to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Lutteropp and Gaudelli are concerned with the use of CRISPR systems for gene editing. Lutteropp teaches hematopoietic stem cells that have an altered epitope that does not alter or affect the natural function of said antigen on the cells, and their use in combination with CAR-T cells which target said epitope. Lutteropp also teaches that CRISPR is one such method of making said altered epitope. Gaudelli teaches the use of an ABE as part of a CRISPR system for making alterations to genomic DNA. One of ordinary skill in the art could use the ABE of Gaudelli to make the altered epitopes of Lutteropp by known methods, with each component of the combination performing their known, usual function, and the combination would yield nothing more than predictable results.
Double Patenting
The nonstatutory 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 nonstatutory 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 nonstatutory 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 nonstatutory 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 1-3, 8-11 and 34-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-82, 89-90, and 92-93 of copending Application No. 18/853,868 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to similar methods.
The '868 application claims a method, comprising administering to a subject in need thereof a population of the genetically engineered hematopoietic cells, which comprise a genomic modification in a gene encoding a lineage-specific cell-surface antigen, wherein the genomic modification alters the amino acid sequence of an epitope that is recognized by an agent that specifically binds the lineage-specific cell-surface antigen resulting in a modified lineage-specific cell-surface antigen, and wherein the modified lineage-specific cell-surface antigen is characterized by reduced binding or no binding of the agent an effective amount of an agent that specifically binds the lineage-specific cell-surface antigen (claim 76-77).
The '868 application further claims that the subject has a hematopoietic malignancy (claim 78).
The '868 application further claims that the agent comprises a single-chain antibody fragment (scFv) (claim 79).
The '868 application further claims that the agent comprises an antibody-drug conjugate (claim 80).
The '868 application further claims that the agent comprises an immune T cell expressing a chimeric antigen receptor (claim 81).
The '868 application further claims that the subject has multiple myeloma (claim 89).
The '868 application further claims that the subject has acute lymphoblastic leukemia (claim 90 and 92).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 9 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 18/033,461 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to similar methods.
The '461 application claims a method, comprising administering to a subject an effective amount of a population of genetically engineered hematopoietic cells, or descendants thereof, comprising a modified gene encoding CD33 that is engineered to have reduced or eliminated expression of a CD33 antigen; and an effective amount of a cytotoxic agent comprising an anti-CD33 antigen-binding domain (claim 1).
The '461 application further claims that the agent comprises an antibody-drug conjugate (claim 2).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644