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 .
Withdrawn Rejections
Applicant’s amendments overcome the rejections of record.
Upon further consideration of the prior art, additional rejection are necessary.
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.
Claim(s) 3, 5, 22-23, 27, 47, 48, 55, 65, 71, 76, 83 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang (WO 2018/227755 A1 pub date:12/20/2018; see translation of WO2018/227755 pp 1-29, 2018) in view Joung (US 11,946,040 B2 patent date:4/2/2024; effectively filed 2/4/2019).
Regarding claims 3, 65, 71, 83, Huang teaches extracting the patient's own hematopoietic stem cells (HSCs) or bone marrow cells, using the base editing system to repair HBB: c.-79A>G and HBB: c.-78A>G mutations, can be accurate at the original locus. Repairing mutation sites is characterized by high efficiency and high safety. Returning the repaired HSC to the patient can cure the patient's severe beta thalassemia (page 4, 2nd full para). These disclosures encompass a method of engrafting nucleobase-edited HSC or progenitors or treating a hemoglobinopathy in a subject comprising contacting a HSC in vitro with a base editing system and administering the base-edited HSC to the subject as claimed. Huang teaches a first aspect of the present invention provides a base editing system for specifically repairing a human HBB gene mutation, comprising: a base editing enzyme and a gRNA, the base editing enzyme being a fusion protein, the fusion protein Including the effector domain of the CRISPR/Cas system, the Cytidine deaminase domain, and the Uracil DNA glycosylase inhibitor (UGI) domain, including but not limited to suppuration Sp-gRNA of Streptococcus pyogenes Cas9 (SpCas9), Sa-gRNA ofStaphylococcus aureus Cas9 (SaCas9), Cj-gRNA of Campylobacter Cas9 (Campylobacter jejuniCas9, CjCas9), St-gRNA of Streptococcus thermophilus Cas9 (StCas9), Nm-gRNA of Neisseriameningitidis Cas9, NmCas9, Lb-gRNA of Cpf1 (Lachnospiraceae Cpf1, LbCpf1), Amino Acid One or more of As-gRNA of the bacterium Cpf1 (Acidaminococcus Cpf1, AsCpf1). Preferably, the gRNA comprises from about 15 to 100 nucleotides and further comprises a leader sequence consisting of at least 12 contiguous nucleotides complementary to the target DNA sequence. Preferably, the sequence in which the gRNA is complementary to the target DNA comprises one or more of the nucleotide sequences set forth in SEQ ID NO. 1 - SEQ ID NO. Specifically, the target DNA sequence complementary to the gRNA leader sequence is a human genomic DNA sequence adjacent to the HBB: c.-79A>G and HBB:c.-78A>G mutations (page 5, second par of Summary of Invention). These teachings encompasses a gRNA and a base editor comprising a polynucleotide programmable DNA binding domain (Cas9 or Cpf1), wherein the gRNA targets the HBB gene or in the promoter region of HBG1/2 as claimed.
Huang does not teach that the deaminase domain is an adenosine deaminase domain and shares at least 85% identity with the sequence of SEQ ID NO:3 and the adenosine deaminase is capable of catalyzing the hydrolytic deamination of adenine or adenosine as claimed.
However Joung teaches adenine base editors (ABEs) having one or more amino acid substitutions that decrease RNA editing activity while still preserving DNA editing activity (col 2, first paragraph under summary). Joung more particularly discloses an ABE with the sequence of SEQ ID NO:34. As seen below, SEQ ID NO:34 has 100% identity with SEQ ID NO:3 of the instant application.
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As such, it would have been obvious to an artisan of ordinary skill before effectively filing to use the ABE variant of SEQ ID NO:34, taught by Joung, as the ABE sequence in the deaminase domain of the adenosine deaminase used in the engraftment method of Huang to predictably arrive at the limitations of claim 3. An artisan would have a reasonable expectation of success because both Huang and Joung provide successfully molecule biology methodology to incorporate SEQ ID NO:34 with the deaminase domain of Huang. Further the artisan would be motivated to use SEQ ID NO:34, taught by Joung, in the deaminase domain and the engraftment method of Huang because Joung teaches their ABE variants decrease RNA editing activity while still preserving DNA editing activity. As such, Huang in view of Joung render claim 3, as amended, obvious.
Regarding claim 5, Huang teaches an A to G nucleobase change as discussed above.
Regarding claim 22, Huang teaches Cas9 as discussed above.
Regarding claims 23 and 27, Huang teaches SpCas9, SaCas9, or variants thereof.
Regarding claims 47, 48, and 55, Huang teaches the HSC has a SNP associated with SCD valine at position 7.
Regarding claim 76, Huang teaches thalassemia.
Allowable Subject Matter
Claims 9, 11, 12, 14, 16, 17, 32, 81, 95 and 115 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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