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 .
Claim Status
Claims 1, 4, 6, 10-13, 15, 17-22, 24, and 62-64 are currently pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 3-8, and 10, in the reply filed on Nov. 14, 2024 is acknowledged. Claims 11-13, 15, 17-22 and 24 are withdrawn for being directed to non-elected subject matter, and claims 1, 4, 6, 10, and 62-64 have been considered on the merits.
Previous Rejections
Status of the rejections:
The previous claim rejections under 101, 102 and 112(a) are withdrawn in view of applicant’s claim amendments. The previous claim rejections under 112(d) are withdrawn in view of applicant’s claim amendments except as specifically maintained below.
Claim Interpretation
Claim 1 is interpreted as a product-by-process with regard to the limitation “differentiated in vitro from stem cells” and “wherein the cells differentiated in vitro from stem cells.” It is emphasized that the claimed invention is directed solely to a product and not a method of making a product.
Claim Rejections - 35 USC § 112(d) (maintained)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Claims 1 is interpreted as a product-by-process with regard to the limitation “differentiated in vitro from stem cells.” There is no structural feature(s) recited in the claim that would distinguish human cells differentiated in vitro from stem cells from differentiated human cells obtained by a different process. Claim 6 has further product-by-process limitations with regard to the origin of the stem cells. There is no structural feature(s) recited in claims 1 or 6 that would distinguish human cells differentiated in vitro from stem cells from a healthy donor from differentiated human cells obtained from an unhealthy donor. For example, bone marrow stem cells obtained from an “unhealthy” individual with high blood pressure may not have any structure/feature different from ones obtained from a healthy individual; however conversely, bone marrow stem cells comprising a GATA2 loss-of-function mutation from being obtained from an individual considered “healthy” because onset of signs and/or symptoms of GATA2 deficiency had not occurred yet in the individual but would occur later in life, such as of a myelodysplastic syndrome or acute myeloid leukemia. Thus, claim 6 does not further limit the claimed product of claim 1 by any feature, either recited or implied, by the process of arriving at the claimed product.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant traverses the previous rejections by arguing claim 6 further limits the human differentiated cells to ones lacking any marker or symptom of a disease of interest, such as a genetic or phenotypic abnormality, citing instant [0054], [0065]-[0066]; however there is no such limiting definition in the specification or claims, and thus, cells derived from a healthy subject encompass cells comprising a genetic marker of a disease as explained above. Further as detailed above, the claims are directed to a product, not a method of making the product, and even “healthy” cells can accumulate genetic or phenotypic abnormalities upon derivation in vitro, especially when propagated in vitro for long durations. Claim 6 puts no limitation on the meaning of “derived” that precludes de novo creation of abnormalities during the process of making the claimed product. In addition, there is currently no test for every marker of every disease.
Claim Rejections - 35 USC § 103 (modified)
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 1, 4, 6, 10, 62, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Pormehr (Pormehr et al., J Cell Biochem 119: 6775-83 (2018)) in view of XM_006723137 (GenBank XM_006723137 posted Mar 26, 2018) as evidenced by Rathnasamy (Rathnasamy et al., Prog Neurobiol 173: 18-40 (2018)).
The claims are interpreted as provided in a previous section.
Pormehr teaches a PRPF31 RNAi knockdown model of retinitis pigmentosa by making compositions (1) comprising differentiated human eye tissue cells in ex vivo retinal explants from healthy donors, which include differentiated mesodermal lineage microglia cells as evidenced by Rathnasamy (Fig. 3; pg. 19, right col., 2nd para.), and (2) comprising an RNA interference (RNAi) molecule targeting PRPF31 expression (siRNA capable of reducing levels of PRPF31’s RNA transcript and PRPF31 protein) (Abstract; pg. 6779, left col., last para., to right col., last para.; Table 1; pg. 6776 right col., 3rd para.; Fig. 3-4; pg. 6779, left col., last para., to right col., last para.).
Regarding claim 1, Pormehr does not teach wherein the RNAi molecule comprises the nucleic acid sequence of any one of SEQ ID NOs :1-3.
However XM_006723137 teaches the human PRPF31 gene, mRNA and amino acid sequences were known in the prior art, and that PRPF31 comprises the DNA sequence (1-1913) analogous to the RNA sequence of instant SEQ ID NO: 1 at position 473-491 as shown below as RNA has the base uracil (U) instead of the DNA base thymine (T).
84.2% identity in 19 residues overlap; Score: 89.0; Gap frequency: 0.0%
SEQ ID NO: 1 1 CGGGAUAAGUACUCAAAGA
XM_006723137 473 CGGGATAAGTACTCAAAGA
***** *** ** ******
It would have been prima facie obvious to one of ordinary skill in the art before the time of filing when performing the method of Pormehr to select the PRPF31 siRNA comprising any RNA sequence targeting the human PRPF31 transcript, such as any sequence in the open reading frame coding region taught by XM_006723137, which teaches the RNA equivalent sequence (100% identity to instant SEQ ID NO: 1) of the DNA gene sequence at 473-491 of human PRPF31 taught by XM_006723137. One of ordinary skill in the art with the goal of modeling PRPF31 reduction-of-function in an in vitro tissue model would be motivated to use the simple and straightforward method of contacting the cells of the tissue with the PRPF31 siRNA targeting at least the complement of SEQ ID NO: 1 of the human PRPF31 transcript as a predictable research tool which inhibits PRPF31 function.
Regarding claim 4, Pormehr teaches the retinal explant composition comprises differentiated mesodermal lineage cells which are microglial cells as evidenced by Rathnasamy (Fig. 3; pg. 19, left col., last para.).
Regarding claim 6, there is no structural feature(s) recited or implied that would distinguish human cells differentiated in vitro from induced pluripotent stem cells (iPSCs), embryonic stem cells, and/or stem cells from a healthy donor from differentiated human cells obtained by a different process. Thus, Pormehr renders obvious the subject matter of claim 6 for the same reasons as set forth fully above for claim 1. Furthermore, Pormehr teaches wherein the human cells are from a healthy donor with no ocular or systemic disease (pg. 6776, right col., 3rd para.).
Regarding claim 10, Pormehr does not teach wherein the RNAi molecule comprises the nucleic acid sequence of SEQ ID NO: 1; however as noted above for claim 1, it would have been prima facie obvious to one of ordinary skill in the art before the time of filing when performing the method of Pormehr to select the PRPF31 siRNA comprising instant SEQ ID NO: 1 of human PRPF31 as taught by XM_006723137. One of ordinary skill in the art with the goal of modeling PRPF31 reduction-of-function in an in vitro tissue model would be motivated to use the simple and straightforward method of contacting the cells of the tissue with the PRPF31 siRNA targeting at least the complement of SEQ ID NO: 1 of the human PRPF31 transcript as a predictable research tool which inhibits PRPF31 function.
Regarding claim 62, Pormehr teaches the RNAi agent (PRPF31 siRNA) caused over 90% reduction of PRPF31 transcripts and 55% reductions in PRPF31 protein as compared to control, and thus reduced PRPF31 activity by at least 20-50% (pg. 6779, left col., last para., to right col., last para.).
Regarding claim 64, Pormehr teaches wherein the healthy subject donor is healthy and lacks any systemic disease (pg. 6776, right col., 3rd para.), and thus, lacks an abnormality associated with a cardiac disease or disorder.
Therefore, the claims as a whole are prima facie obvious to one of ordinary skill in the art before the earliest effective time of filing.
Response to Arguments
Applicant traverses the previous rejections (pg. 8-9) by arguing Pormehr relates solely to RPE cells that are not of a mesodermal lineage; however to the contrary, Pormehr relates to intact retinal explant tissues, which comprise various cell types, including cells of a mesodermal lineage (e.g., hemopoetic and/or immune) as evidenced by Rathnasamy, as well as neuronal cell types such as RPE.
Allowable Subject Matter
Claim 63 is 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.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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, Tracy Vivlemore can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638