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 .
Note
Please note that Khaleda Bhuiya Hasan is now the examiner of record.
Application Status
This action is written in response to applicant’s correspondence received 08/20/2025. Claims 152-171 are currently pending. Claims 156, 158, and 162-171 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 152-155, 157, and 159-161 are examined herein. The restriction requirement mailed 2/24/2025 is still deemed proper. Applicant's elected Group I, claims 152-161 and species of amino acid linker (as cited in claim 157) and RNA-dependent DNA polymerase (as cited in claim 159) without traverse in the reply filed 08/20/2025.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 7 and 37. 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 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 152-155, 157, and 159-161 are rejected under 35 U.S.C. 103 as being unpatentable over Weinstein (US20120159653A1; published 6/21/2012; cited in the PTO-892 mailed 2/24/2025), in view of Scharenberg (WO2018200597A1; published 11/1/2018; cited in the PTO-892 mailed 2/24/2025).
Weinstein’s disclosure is drawn to genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with macular degeneration, using a zinc finger nuclease-mediated editing process (abstract).
Regarding claim 152, Weinstein teaches zinc finger nucleases (ZFN) comprising a DNA binding domain and a cleavage domain or nuclease (para 0033) wherein two ZFNs are required for cleavage (para 0040). Weinstein further teaches a ZFN comprising two cleavage monomers to form an active enzyme dimer that can be derived from different endonucleases (paras 0040-0045). Weinstein teaches ZFNs comprising the cleavage domain from FokI, whose cleavage domain is separable from the binding domain and this FokI is active as dimer (paras 0042-0043). Weinstein further teaches that for targeted double-stranded cleavage using a FokI cleavage domain, two ZFNs, each comprising a FokI cleavage monomer, can be used to reconstitute an active enzyme dimer (para 0043). Weinstein teaches that for integrating a sequence encoding a target protein associated with a disease, a double stranded break introduced into the chromosomal sequence by the ZFN is repaired, via homologous recombination with the donor polynucleotide (i.e. corresponding to the target sequence) wherein the donor polynucleotide can be used as a template for repairing the break (para 0054). Weinstein further teaches the donor polynucleotide comprising a linear piece of DNA or a PCR fragment (paras 0048 and 0056). Weinstein teaches polynucleotides encoding ZFN introduced into fertilized embryo for targeting ApoE locus wherein the targeted region of the ApoE locus is PCR amplified using appropriate primers (i.e. interpreted as requiring a DNA synthesis template that must have a primer binding site and uses a polymerase to synthesize and amplify the targeted region) (Example 2; para 0093). Weinstein teaches that a target nucleic acid sequence refers to the chromosomal sequence to be edited (i.e. the donor template sequence) and to which a ZFN is engineered to recognize and bind, provided sufficient conditions for binding exist (para 0084). Weinstein further teaches that the ZFN may comprise a nuclear localization signal (NLS) that facilitates targeting the ZFN protein into the nucleus to introduce a double stranded break at the target sequence in the chromosome (NLS is also well-known in the art as indicted by Weinstein and known for its nuclear localization function transporting proteins such as DNA polymerase, in the repair process) (para 0038).
However, Weinstein does not teach a ZFN gene editing compositions comprising a polymerase.
Scharenberg’s disclosure is directed to improved compositions for the homology directed repair of the human globin locus for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy (abstract).
Regarding claim 152, Scharenberg teaches that ZFNs comprising one or more DNA binding domains, and an endonuclease domain or endonuclease half-domain (i.e. referring to actively functional domain that can function without a dimer) and one or more linkers or additional functional domains, e.g. an end processing enzymatic domain that exhibits exonuclease, endonuclease, helicase or DNA polymerase activity wherein ZFN and DNA end processing enzyme can be introduced separately into vectors and one of the examples of DNA end processing enzyme include DNA polymerase (pg. 50, lines 7-18; pg. 51, lines 1-30; pg. 52, lines 1-27; pg. 57, lines 1-4). Scharenberg further teaches a DNA repair template (for editing a target gene) comprising a 5’ or 3’ homology arm wherein the donor repair template comprises a polynucleotide sequence within upstream of the transcription start site of the target gene (pg. 2, lines 17-21).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Weinstein’s gene editing compositions by substituting one of the ZFN active nuclease domains of Weinstein for the active nuclease half-domain with a polymerase, as taught by Scharenberg because it would have amounted to a simple substitution of one known ZFN active nuclease domain for a ZFN half-domains with an additional domain that exhibits polymerase activity or a DNA polymerase involved in DNA end processing taught by Scharenberg to obtain predictable results. One would have had a reasonable expectation of success because both Weinstein and Scharenberg teach the method of genome-editing using zinc finger nuclease for treating a genetic disease. Thus, the claimed invention as a whole is prima facie obvious.
Regarding claim 153, Scharenberg teaches that the extension arm comprising a DNA synthesis template and a primer binding site is chemically coupled to the ZFN with an inactive nuclease domain (pg. 52, lines 3-27).
Regarding claim 154, Weinstein teaches that the active nuclease domain is a FokI nuclease domain (paras 0040-0043).
Regarding claim 155, Weinstein teaches the inactive domain can be a FokI nuclease domain (paras 0044-0045).
Regarding claim 157, Scharenberg teaches gene editing compositions that can comprise one or more linkers to attached the ZFN to a polymerase (pg. 50, lines 7-18; pg. 57, lines 1-4).
Regarding claim 159, Scharenberg teaches that the polymerase RNA-dependent DNA polymerase (pg. 50, lines 7-18; pg. 57, lines 1-4).
Regarding claim 160, Scharenberg teaches gene editing compositions can further comprise a helicase (pg. 50, lines 7-18; pg. 57, lines 1-4).
Regarding claim 161, Scharenberg teaches gene editing compositions further comprising FEN1 (pg. 50, lines 7-18; pg. 57, lines 1-14).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636