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 .
This action is in response to the amendment filed 04/23/2026, in which claims 130, 133, 138, 140 and 142 were amended, claims 131, 132, 135, 136, 141, 143 and 144 were previously presented and claims 145-159 were withdrawn from consideration in a previous office action. Claims 130-133, 135, 136, 138 and 140-144 are currently pending.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn. This action is FINAL.
Claim Rejections - 35 USC § 112
The previous rejection of claim 138 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendments to the claims filed on 04/23/2026.
The previous rejection of claims 138 and 140-144 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendments to the claims filed on 04/23/2026.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 140 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The claim is interpreted as reading on a human organism because the instant specification describes the cell is from a subject wherein the subject is a human [0004, 0011, 00109, 00117, 00126, 00134, 00144, 00146 and 00195]. Therefore, the cell reads on a human organism.
Response to Arguments - Claim Rejections - 35 USC § 101
The previous rejection of claim 140 under 35 U.S.C. 101 has been maintained in view of Applicant’s arguments filed on 04/23/2026. Applicant’s arguments and amendments have been fully considered but have not been found persuasive.
Applicant argues the claim cannot be interpreted as being directed to or encompassing a “human organism”. Applicant continues to argue that the term “human organism”, while intended to include human embryos and fetuses, it is not intended to include a cell from a human.
Applicant’s arguments are not persuasive because the current claim limitation does not specify the cell that would be comprise the composition of instant claim 130. Therefore, the current claim limitations do include any cell from a human organism, including but not limited to, a human embryo or fetus. It would be remedial to amend the claim to recite the specific cell comprising the composition or amending the claim to recite “an isolated cell”.
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 130-133, 135, 136, 138, 140-142 and 144 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Suzuki et al (Nature. 2016 December 01; 540(7631): 144–149). This is a NEW Rejection necessitated by the amendment filed on 04/23/2026.
Regarding claims 130-133, Suzuki teaches a HITI-AAV vector for inserting a copy of Mertk exon 2 into intron 1 (AAV-rMertk-HITI) and an HDR-AAV vector (AAV-rMertk-HDR) as a control (Page 5, Paragraph 3). Suzuki teaches pAAVrMertk-HITI, exon 2 of rat Mertk gene including the surrounding intron is sandwiched by Cas9/gRNA target sequence, which is expected to integrate within intron 1 of Mertk by HITI and the homology arms were amplified by PCR from mouse and rat genome DNA, and subcloned into AAV backbone plasmid (Page 7, last paragraph and Page 42, Fig. 3). The pAAVrMertk-HITI construct comprises a single homology arm construct comprising a replacement sequence and a Cas9 cleavage site in reverse orientation with respect to the replacement sequence, and a Cas9 protein wherein the replacement sequence comprises at least one nucleotide difference compared to a target genome and wherein the target genome comprises a sequence homologous to the targeted Cas9 site (Page 42, Fig. 3).
Regarding claims 135 and 136, Suzuki teaches pAAVrMertk-HITI, exon 2 of rat Mertk gene including the surrounding intron is sandwiched by Cas9/gRNA target sequence, which is expected to integrate within intron 1 of Mertk by HITI and the homology arms were amplified by PCR from mouse and rat genome DNA, and subcloned into AAV backbone plasmid (Page 7, last paragraph and Page 42, Fig. 3).
Regarding claim 138, Suzuki teaches a HITI-AAV vector for inserting a copy of Mertk exon 2 into intron 1 (AAV-rMertk-HITI) and an HDR-AAV vector (AAV-rMertk-HDR) as a control (Page 5, Paragraph 3). Suzuki teaches pAAVrMertk-HITI, exon 2 of rat Mertk gene including the surrounding intron is sandwiched by Cas9/gRNA target sequence, which is expected to integrate within intron 1 of Mertk by HITI and the homology arms were amplified by PCR from mouse and rat genome DNA, and subcloned into AAV backbone plasmid (Page 7, last paragraph and Page 42, Fig. 3).
Regarding claims 140 and 141, Suzuki teaches the AAV vector comprising the construct is injected in to the subretinal space of the RCS rats for transductions of the cells within the subretinal space (Page 5, Paragraph 3).
Regarding claims 142 and 144, Suzuki teaches a HITI-AAV vector for inserting a copy of Mertk exon 2 into intron 1 (AAV-rMertk-HITI) and an HDR-AAV vector (AAV-rMertk-HDR) as a control (Page 5, Paragraph 3). Suzuki teaches pAAVrMertk-HITI, exon 2 of rat Mertk gene including the surrounding intron is sandwiched by Cas9/gRNA target sequence, which is expected to integrate within intron 1 of Mertk by HITI and the homology arms were amplified by PCR from mouse and rat genome DNA, and subcloned into AAV backbone plasmid (Page 7, last paragraph and Page 42, Fig. 3). The pAAVrMertk-HITI construct comprises a single homology arm construct comprising a replacement sequence and a Cas9 cleavage site in reverse orientation with respect to the replacement sequence, and a Cas9 protein wherein the replacement sequence comprises at least one nucleotide difference compared to a target genome and wherein the target genome comprises a sequence homologous to the targeted Cas9 site (Page 42, Fig. 3).
Claim Rejections - 35 USC § 102
The previous rejections of claims 130-133, 135-136, 138, 140-142 and 144 under 35 U.S.C. 102(a)(1) as being anticipated by Zhu et al (Stem Cell Reports, Vol 4, pgs 1103-1111 and Supplemental Pages 1/18-18/18; 2015) has been withdrawn in view of Applicant’s amendments to the claims filed on 04/23/2026.
The previous rejections of claims 130-133, 135, 138, 140-142 and 144 under 35 U.S.C. 102(a)(1) as being anticipated by Basiri et al (Cell J. 2017; 18(4): 532-539) has been withdrawn in view of Applicant’s amendments to the claims filed on 04/23/2026.
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.
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.
Claim 143 is rejected under 35 U.S.C. 103 as being unpatentable over Suzuki et al (Nature. 2016 December 01; 540(7631): 144–149) in view of Guo et al (WO 2017/214615 A1; Cited in a previously mailed office action). This is a NEW Rejection necessitated by the amendment filed on 04/23/2026.
The teachings of Suzuki are described above and applied as before.
Suzuki does not teach the plasmid containing the guide oligonucleotide, the targeted endonuclease and the donor construct on one single plasmid.
Guo teaches the gRNA and donor nucleic acids are introduced to a target cell encoded on the same vector, such as a plasmid, to ensure that a host cell will have both components, rather than requiring a host cell to be transformed by two different vectors [40]. Guo teaches that this greatly increases the efficiency of successful transformations over approaches in which gRNA and donor are encoded on separate molecules [40].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Suzuki to include the gRNA and donor nucleic acids are introduced to a target cell encoded on the same vector, such as a plasmid as taught by Guo because Suzuki teaches it is within the ordinary skill in the art to use a pAAVrMertk-HITI vector comprising exon 2 of rat Mertk gene including the surrounding intron is sandwiched by Cas9/gRNA target sequence, which is expected to integrate within intron 1 of Mertk by HITI and the homology arms were amplified by PCR from mouse and rat genome DNA, and subcloned into AAV backbone plasmid and Guo teaches the gRNA and donor nucleic acids are introduced to a target cell encoded on the same vector, such as a plasmid, to ensure that a host cell will have both components, rather than requiring a host cell to be transformed by two different vectors.
One would have been motivated to make such a modification in order to receive the expected benefit of ensuring all necessary components are delivered to the target cell as well as increased efficiency of successful transformations as taught by Guo.
Claim Rejections - 35 USC § 103
The previous rejection of claim 143 under 35 U.S.C. 103 as being unpatentable by Zhu et al (Stem Cell Reports, Vol 4, pgs 1103-1111; 2015) in view of Guo et al (WO 2017/214615 A1) has been withdrawn in view of Applicant’s amendments to the claims filed on 04/23/2026.
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/ Examiner, Art Unit 1637
/CELINE X QIAN/ Primary Examiner, Art Unit 1637
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