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 .
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/US21/35691, filed
03 June 2021. Acknowledgment is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 63/183791, filed 04 May 2021, and US Provisional Application Nos. 63/033966 and 63/033970, each filed 03 June 2020.
Election/Restrictions
Applicant’s election without traverse of Group I, encompassing claims 1-2, 4, 16, 20-21, 49, 51, and 58, in the reply filed on 07 January 2026 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. Accordingly, claims 5-6, 22-24, 27-29, 39, 41, and 45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1-2, 4-6, 16, 20-24, 27-29, 39, 41, 45, 49, 51, and 58, of record 07 January 2026, are pending. Claims 5-6, 22-24, 27-29, 39, 41, and 45 are withdrawn for reading on the non-elected inventions. Prosecution on the merits commences for claims 1-2, 4, 16, 20-21, 49, 51, and 58.
Specification
The substitute Specification filed 30 November 2022 is acknowledged and entered into the application file.
The lengthy Specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the Specification.
However, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in Pages 48, 118, 120, and 124. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
It is of note that although the recitation of a “genetically engineered hematopoietic stem or progenitor cell” is in the preamble of independent claim 1, the disclosure of the genetically engineered hematopoietic stem or progenitor cell is necessary to give life, meaning, and vitality to the claim. Therefore, the preamble is afforded patentable weight and thereby limits the scope of the claim. See MPEP § 2111.02.
Under the broadest reasonable interpretation of instant claims 49, 51, and 58, all of the “optional” limitations are not required.
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 1-2, 4, 16, 20-21, 49, 51, and 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mukherjee et al (WO 2019/046285 A1, of record on IDS filed 30 November 2022). Mukherjee et al has a publication date of 07 March 2019, which is greater than one year prior to the effective filing date of the instant invention.
Mukherjee et al disclose compositions and methods relating to agents that target a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies (Abstract).
As such, Mukherjee et al disclose CD34+ hematopoietic stem cells genetically engineered to comprise an altered exon 2 of the endogenous CD33 gene via a modified CRISPR/Cas9 base editor system, wherein the CRISPR/Cas9 base editor system causes a G to A nucleotide substitution for the four G’s within the splice acceptor and exonic splicing enhancer binding site (C to T nucleotide substitution on the reverse strand), resulting in a reduced expression of exon 2 epitope when compared to a wild-type cell (Pages 3-6, 8-9, 48-49, 54-59, 84-87; Figure 19; Example 5). Mukherjee et al further disclose CD34+ hematopoietic stem cells that comprise single nucleotide polymorphism (SNP) rs12459419 in exon 2 of the CD33 gene, wherein the rs12459419 SNP results in a C to T nucleotide substitution (Pages 3-5, 8, 54-56, 84-85).
Mukherjee et al further disclose a method of treating a hematopoietic malignancy, wherein an effective amount of an agent comprising an antigen-binding fragment specific for CD33 is first administered to a human subject suffering from the hematopoietic malignancy, followed by the administration of a population of the genetically engineered hematopoietic stem cells (Pages 3, 5-6, 14, 84-87; Example 5). Mukherjee et al further disclose that the hematopoietic malignancy is Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, or multiple myeloma (Pages 4, 7, 66-69, 54-55, 59, 62-66, 86).
Accordingly, Mukherjee et al anticipate the claims as follows:
Regarding claims 1-2, 4, and 16: Mukherjee et al disclose CD34+ (claim 16) hematopoietic stem cells genetically engineered to comprise an altered exon 2 of the endogenous CD33 gene via a modified CRISPR/Cas9 base editor system, wherein the CRISPR/Cas9 base editor system causes a G to A nucleotide substitution for the four G’s within the splice acceptor and exonic splicing enhancer site (claims 2, 4), resulting in a reduced expression of exon 2 epitope when compared to a wild-type cell. This therefore reads on the genetically engineered hematopoietic stem or progenitor cell of instant claim 1.
Regarding claim 20: Following the discussion of claim 1, Mukherjee et al further disclose that the CRISPR/Cas9 base editor system is a BE2 or BE3 system (Page 49). As these are the same base editor systems utilized within the instant disclosure, the genetically engineered hematopoietic stem cells will inherently not comprise a mutation in any predicated off-target sites. See Pages 94-95 of the instant disclosure and MPEP See MPEP § 2112.01(I). This therefore reads on the genetically engineered hematopoietic stem or progenitor cell of the instant claim.
Regarding claim 21: Following the discussion of claim 1, Mukherjee et al further disclose a population of the genetically engineered hematopoietic stem cells. This therefore reads on the cell population of the instant claim.
Regarding claims 49 and 51: Following the discussion of claim 1, Mukherjee et al further disclose a method of treating a hematopoietic malignancy, wherein an effective amount of an agent comprising an antigen-binding fragment specific for CD33 is first administered to a human subject suffering from the hematopoietic malignancy (claim 51), followed by the administration of a population of the genetically engineered hematopoietic stem cells (claim 49). This therefore reads on the method of the instant claims.
Regarding claim 58: Following the discussion of claim 49, Mukherjee et al further disclose that the hematopoietic malignancy is Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, or multiple myeloma. This therefore reads on the method of the instant claim.
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 1-2, 4, 16, 20-21, 49, 51, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, and 11 of U.S. Patent No. 11,718,659 B2 in view of Mukherjee et al (WO 2019/046285 A1, of record on IDS filed 30 November 2022).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims. More specifically, the patented claims are not identical because no single patented claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate patent claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the patent, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
Patent claim 1 is directed to a method, comprising administering to a subject in need thereof:
(i) an effective amount of an agent targeting CD33, wherein the agent comprises an antigen-binding fragment that binds CD33, and
(ii) a population of hematopoietic cells that are genetically engineered to comprise a mature transcript of CD33 having a mutated exon 2 and wherein the hematopoietic cells are engineered by a CRISPR-Cas system comprising one or more guide nucleic acids comprising a sequence according to any one of SEQ ID NO: 52-61.
It is of note that the guide nucleic acid comprising a sequence according to SEQ ID NO: 58 converts the four G's within the splice acceptor and ESE to A's (C>T on reverse strand), resulting in loss of splice acceptor and/or ESE site of exon 2. See Table 7 and Column 48 of the patent.
Patent claims 5-6 further limit the method of patent claim 1, wherein the subject has a hematopoietic malignancy associated with CD33 expression, or leukemia.
The combination of patent claims 1 and 5-6 do not teach that the population of hematopoietic cells that are genetically engineered to comprise a mature transcript of CD33 having a mutated exon 2 have a reduced expression level of an epitope encoded by exon 2 od CD33 as compared with a wildtype counterpart cell.
Mukherjee et al, however, disclose hematopoietic stem cells genetically engineered to comprise an altered exon 2 of the endogenous CD33 gene via a modified CRISPR/Cas9 base editor system, wherein the CRISPR/Cas9 base editor system causes a G to A nucleotide substitution for the four G’s within the splice acceptor and exonic splicing enhancer binding site (C to T nucleotide substitution on the reverse strand), resulting in a reduced expression of exon 2 epitope when compared to a wild-type cell (Pages 3-6, 8-9, 48-49, 54-59, 84-87; Figure 19; Example 5).
Therefore, it would have been prima facie obvious to have substituted the mutated CD33 exon 2 of the patent claim with the mutated CD33 exon 2 of Mukherjee et al, as doing so would have been a simple substitution of one mutated CD33 exon 2 for another. One of ordinary skill in the art would have recognized that the two mutated CD33 exons are functionally comparable, as they both are the result of converting the four G's within the splice acceptor and ESE to A's, and thereby would have been able to substitute the mutated CD33 exons with predictable results.
Consequently, patent claims 1 and 5-6 in view of Mukherjee et al render obvious a method of treating a hematopoietic disorder within a subject, wherein the subject suffers from leukemia and is administered:
(i) an effective amount of an agent targeting CD33, wherein the agent comprises an antigen-binding fragment that binds CD33, and
(ii) a population of hematopoietic cells that are genetically engineered to comprise an altered splice acceptor or exonic splicing enhancer site in exon 2 of an endogenous CD33 gene, and wherein the alteration causes a reduced expression level of an epitope encoded by exon 2 of CD33 as compared with a wild-type counterpart cell.
This therefore renders obvious the method of instant claims 49, 51, and 58, as well as the genetically engineered hematopoietic stem or progenitor cell of instant claim 1-3 and population of cells thereof of instant claim 21.
With that, instant claims 16 and 21 are known from the patent claims or prior art and can be further incorporated into the method rendered obvious by patent claims 1 and 5-6 in view of Mukherjee et al:
Patent claim 11 further limits the method of patent claim 1, wherein the hematopoietic cells are CD34+ hematopoietic stem cells. This therefore renders obvious the genetically engineered hematopoietic stem or progenitor cell of instant claim 16.
Mukherjee et al further teach the limitation recited in instant claim 20.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633