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 .
Applicant's response to the previous Office action, dated May 5, 2026, has been received. By way of this submission, Applicant has amended claim 1, and cancelled claims 2-3, 16-17, and 22-23.
Claims 1, 8-11, 26-28, 34-36, and 61-63 are pending in the application. Claim 27 remains withdrawn from consideration, pursuant to the Restriction Requirement mailed April 8, 2025.
Claims 1, 8-11, 26, 28, 34-36, and 61-63 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated November 5, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 5, 2025 was filed after the mailing date of the first Office action on the merits on November 5, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
Claims 1-3, 8-11, 16-17, 22-23, 26, 28, 34-36, and 61-63 were previously 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.
Applicant's amendments to the claims have addressed this issue, and this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 102
Claims 1-3, 8, 10-11, 16-17, 22, 28, 34-36 and 61 were previously 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).
Applicant's amendments to the claims have addressed this issue, as Lutteropp does not teach the claimed epitopes of CD33. This rejection is hereby withdrawn.
Claims 1, 3, 8-11, 22-23, 26, 28, 34-36, and 61 were previously 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).
Applicant's amendments to the claims have addressed this issue, as Mukherjee does not teach the claimed epitopes of CD33. This rejection is hereby withdrawn.
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 § 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 were previously 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).
Applicant's amendments to the claims have addressed this issue, as Mukherjee does not teach the claimed epitopes of CD33. This rejection is hereby withdrawn.
Claims 1, 8-11, 26, 28, 34-36, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Mukherjee (US20170326179A1, cited in IDS as U.S. patent 10,137,155) in view of Laszlo (Oncotarget. 2016 Jul 12;7(28):43281-43294, cited in IDS). This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
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).
Mukherjee further teaches that cell-surface lineage-specific antigen has a portion deleted (para. 0138).
Mukherjee further teaches that cell-surface lineage-specific antigen is CD33 (para. 0140).
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 (i.e., a cytotoxic agent comprising an antibody or an antigen-binding fragment thereof) (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 hematopoietic stem cells may be isolated from bone marrow or peripheral blood mononuclear cells (PBMCs) and may be allogeneic or autologous (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.
However, Mukherjee does not teach the claimed epitopes of CD33.
Laszlo teaches that variants of CD33 lacking exon 2 are found in specimens of acute myeloid leukemia (AML)(Figure 1). Laszlo teaches that directing therapies to CD33 variants may be useful in treating malignancies which express said variant CD33 (page 43290, left column, first paragraph and right column, second paragraph). According to Applicant's specification at pages 71-73, exon 2 of CD33 encompasses residues 44-52 of the CD33 protein sequence. Under the broadest reasonable interpretation of claim 37, a complete deletion of exon 2 of CD33 would result in a variant CD33 which lack a non-essential epitope comprising amino acids 47-51 (SEQ ID NO: 9) and 48-52 (SEQ ID NO: 12) of CD33.
Laszlo further teaches assays with cells bearing a variant of CD33 and the antibody-drug conjugate gemtuzumab ozogamicin, and that cells lacking exon 2 of CD33 could not be targeted by the conjugate (see, e.g., Figure 9).
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 Mukherjee and Laszlo to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since Mukherjee teaches that variants of CD33 are useful in treating hematological malignancies by targeting CD33 with an antigen-binding compound. Following the teachings of Laszlo, which recites variants of CD33 which may not bind to established antibodies, the skilled artisan could take cells which are lacking exon 2 of CD33 and devise a treatment by following the teachings of Mukherjee to arrive at the claimed invention. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Claims 62 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Mukherjee and Laszlo as applied to claim 61 above, and further in view of Gaudelli (Nature, 2017 Nov 23;551(7681):464-471, cited previously). This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
The teachings of Mukherjee and Laszlo have been discussed supra. However, Mukherjee and Laszlo do 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 Mukherjee, Laszlo, 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 Mukherjee and Gaudelli are concerned with the use of CRISPR systems for gene editing. Mukherjee teaches hematopoietic stem cells that have an altered epitope of CD33 that does not alter or affect the natural function of said antigen on the cells, and their use in combination with CAR-T cells and antibody-drug conjugates which target said epitope. Mukherjee 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 Mukherjee 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 were previously 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).
Claims 1 and 9 were previously 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.
Applicant's amendments to the claims have addressed these issues, and the above rejections are hereby withdrawn.
Claims 1, 8-11, 26, 28, 34-36, and 61-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-77 of copending Application No. 18/853,868 (reference application) in view of Mukherjee, Laszlo, and Gaudelli. This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
The '868 application claims a method, comprising administering to a subject in need thereof a genetically engineered hematopoietic cell, or descendant thereof, comprising 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 (claim 76).
The '868 application further claims administering an effective amount of an agent that specifically binds the lineage- specific cell-surface antigen and/or wherein the subject has a hematopoietic malignancy (claim 77).
However, the '868 application does not claim the epitopes of CD33 in question.
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).
Mukherjee further teaches that cell-surface lineage-specific antigen has a portion deleted (para. 0138).
Mukherjee further teaches that cell-surface lineage-specific antigen is CD33 (para. 0140).
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 (i.e., a cytotoxic agent comprising an antibody or an antigen-binding fragment thereof) (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 hematopoietic stem cells may be isolated from bone marrow or peripheral blood mononuclear cells (PBMCs) and may be allogeneic or autologous (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.
However, Mukherjee does not teach the claimed epitopes of CD33.
Laszlo teaches that variants of CD33 lacking exon 2 are found in specimens of acute myeloid leukemia (AML)(Figure 1). Laszlo teaches that directing therapies to CD33 variants may be useful in treating malignancies which express said variant CD33 (page 43290, left column, first paragraph and right column, second paragraph). According to Applicant's specification at pages 72-74, exon 2 of CD33 encompasses residues 44-52 of the CD33 protein sequence. Under the broadest reasonable interpretation of claim 37, a complete deletion of exon 2 of CD33 would result in a variant CD33 which lack a non-essential epitope comprising amino acids 47-51 (SEQ ID NO: 9) and 48-52 (SEQ ID NO: 12) of CD33.
Laszlo further teaches assays with cells bearing a variant of CD33 and the antibody-drug conjugate gemtuzumab ozogamicin, and that cells lacking exon 2 of CD33 could not be targeted by the conjugate (see, e.g., Figure 9).
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), which is pertinent to claims 62-63.
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 claims of the '868 application with the teachings of Mukherjee, Laszlo, and Gaudelli to arrive at the claimed invention. Both the '868 application and Mukherjee teach methods of administering genetically engineered hematopoietic cells with modified versions of CD33 that prevents binding by an agent. Lazlo teaches that deletion of exon 2, which includes the instant claimed deleted epitopes of CD33, is one method to abolish of a CD33-binding agent. Additional features of the claimed invention are taught by Mukherjee and Gaudelli. One of ordinary skill could apply the methods of Mukherjee and Gaudelli with the CD33 mutant of Laszlo to the claims of the '868 application to arrive at the instantly claimed invention by known methods, with each component of the combination performing their known, usual function, and the combination would yield nothing more than predictable results.
Claims 1, 8-11, 26, 28, 34-36, and 61-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 30, and 59 of copending Application No. 18/033,461 (reference application) in view of Mukherjee, Laszlo, and Gaudelli. This is a new grounds of rejection, necessitated by Applicant's amendments to the claims.
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 the cytotoxic agent is an antibody-drug conjugate (claim 2).
The '461 application further claims the subject has a hematopoietic malignancy (claim 30).
However, the '461 application does not claim the epitopes of CD33 in question.
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).
Mukherjee further teaches that cell-surface lineage-specific antigen has a portion deleted (para. 0138).
Mukherjee further teaches that cell-surface lineage-specific antigen is CD33 (para. 0140).
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 (i.e., a cytotoxic agent comprising an antibody or an antigen-binding fragment thereof) (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 hematopoietic stem cells may be isolated from bone marrow or peripheral blood mononuclear cells (PBMCs) and may be allogeneic or autologous (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.
However, Mukherjee does not teach the claimed epitopes of CD33.
Laszlo teaches that variants of CD33 lacking exon 2 are found in specimens of acute myeloid leukemia (AML)(Figure 1). Laszlo teaches that directing therapies to CD33 variants may be useful in treating malignancies which express said variant CD33 (page 43290, left column, first paragraph and right column, second paragraph). According to Applicant's specification at pages 72-74, exon 2 of CD33 encompasses residues 44-52 of the CD33 protein sequence. Under the broadest reasonable interpretation of claim 37, a complete deletion of exon 2 of CD33 would result in a variant CD33 which lack a non-essential epitope comprising amino acids 47-51 (SEQ ID NO: 9) and 48-52 (SEQ ID NO: 12) of CD33.
Laszlo further teaches assays with cells bearing a variant of CD33 and the antibody-drug conjugate gemtuzumab ozogamicin, and that cells lacking exon 2 of CD33 could not be targeted by the conjugate (see, e.g., Figure 9).
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), which is pertinent to claims 62-63.
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 claims of the '461 application with the teachings of Mukherjee, Laszlo, and Gaudelli to arrive at the claimed invention. 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 claims of the '461 application with the teachings of Mukherjee, Laszlo, and Gaudelli to arrive at the claimed invention. Both the '461 application and Mukherjee teach methods of administering genetically engineered hematopoietic cells with modified versions of CD33 that prevents binding by an agent. Lazlo teaches that deletion of exon 2, which includes the instant claimed deleted epitopes of CD33, is one method to abolish of a CD33-binding agent. Additional features of the claimed invention are taught by Mukherjee and Gaudelli. One of ordinary skill could apply the methods of Mukherjee and Gaudelli with the CD33 mutant of Laszlo to the claims of the '461 application to arrive at the instantly claimed invention by known methods, with each component of the combination performing their known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is 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.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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