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 .
Application Status
Applicant’s remarks and amendments to the claims filed August 31, 2026 are acknowledged. Claims 11, 16-17, and 25 were amended. Claims 1-11, 13-17, 19-22, and 24-25 are pending.
Restriction/Election
Applicant’s election of Group II (claims 16-17, and 19-22) in the reply filed on August 31, 2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 1-11, 13-15, and 24-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 16-17, and 19-22 are under consideration hereinafter.
Priority
Applicant’s priority claims to Application Nos. 63/159,937 and PCT/US2022/019989 are acknowledged. Claims 16-17, and 19-22 find support in Application No. 63/159,937. The effective filing date of the claims under examination is March 11, 2021.
Specification
The specification is objected to because of the following informalities:
The use of terms which are trade names or marks used in commerce has been noted in this application, e.g., “StemSpan” (pg. 48), “Cytofix,” “SYBER,” (pg. 49), and others throughout the disclosure. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. The terms, including the exemplary terms above, should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The Brief Description of The Drawings makes reference to color drawings (at least pg. 8, line 31; pg. 9, line 26; pg. 12, line 28). Examiner notes that color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. No such petition has been filed or accepted in this application. Examiner recommends either I) removing the reference to color drawings, or alternatively, II) filing a petition to accept color drawings, as well as color drawings should the petition be granted.
The disclosure is objected to because it contains embedded hyperlinks and/or other form of browser-executable code, i.e., http://www.crapome.org/ (pg. 42, line 8), and http://pantherdb.org (pg. 42, line 19), and the hyperlinks in the resources table on pg. 50. Applicant is required to delete the embedded hyperlinks 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.
Appropriate correction is required.
Drawings
The drawings are objected to because of the following informalities:
The drawings filed May 26, 2026 are objected to because they were submitted in color, but there is no granted petition to accept color drawings. See Fig. 1B, specifically. See 37 CFR 1.84(a)(2) (“The Office will accept color drawings in utility patent applications only after granting a petition filed under this paragraph explaining why the color drawings are necessary”). Applicants must either provide that explanation via a petition and comply with all requirements of 37 CFR 1.84(a)(2)(i)-(iii) OR submit replacement sheets in black and white and include a clear instruction to replace the color drawings with the replacement sheets. Examiner takes no position on whether color drawings are necessary as the only practical medium by which to disclose the subject matter sought to be patented in this utility patent application.
Appropriate correction is required.
Claim Objections
Claims 16-17 are objected to because of the following informalities:
Claim 16 recites “an shRNA of SEQ ID NO: 52 or SEQ ID NO: 43,” and “an siRNA of SEQ ID NO: 51 or SEQ ID NO: 42.” Based on the disclosure, the sequences set forth in the sequence listing, and knowledge of shRNA and siRNA structure in the prior art, it is reasonably clear that the claims intend to encompass an shRNA or siRNA comprising one of the recited sequences. The claim should be amended to recite “an shRNA comprising[[of]] SEQ ID NO: 52 or SEQ ID NO: 43,” and “an siRNA comprising[[of]] SEQ ID NO: 51 or SEQ ID NO: 42,” accordingly.
Claim 16 recites “hybrides” which should be amended to “hybridizes.”
Claim 17 recites “wherein said synthetic nucleic acid… targets and inhibits expression of ZNF622 contiguous nucleic acid of SEQ ID NO: 36.” Based on the specification, SEQ ID NO: 36 corresponds to a ZNF622 mRNA, and the recited synthetic nucleic acid molecules target a portion of SEQ ID NO: 36 and inhibit ZNF622 expression (Fig. 15A-B). It would be preferable, accordingly, to amend the claim to recite “wherein said synthetic nucleic acid molecule… targets and inhibits expression of the ZNF622 mRNA set forth in
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16-17, and 19-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites a “composition for reducing expression of ZNF622, comprising a synthetic nucleic acid molecule… said composition being selected from i) an shRNA of SEQ ID NO: 52 or SEQ ID NO: 43…” (emphasis added). Based on the italicized phrase, it appears that the composition for reducing expression of ZNF622 is one of (i)-(iv). This confusing because the claim previously states that the composition “compri[ses] a synthetic nucleic acid molecule,” which would be interpreted as encompassing a synthetic nucleic acid molecule (e.g., one of (i)-(iv)) in a mixture with one or more additional elements. Given the conflicting scope of the two phrases, the scope of the claim is unclear. The skilled artisan would not know whether the claim is directed to a composition which is one of (i)-(iv), or whether the claim is directed to a composition comprising one of (i)-(iv).
Claims 17, and 19-22 are rejected for depending from claim 16 and failing to remedy the indefiniteness. In the interest of compact prosecution, the claims will be interpreted hereinafter as being directed to a composition comprising one of (i)-(iv), wherein the term “synthetic nucleic acid molecule” is understood to refer to (i)-(iv). This interpretation is cohesive with dependent claims 17, and 19-20, which require additional elements, e.g., modifications for increased stability and/or uptake (see specification, pg. 22-26), a vector, or elements of a formulation.
Claim 16 recites “a guide strand selected from at least one of SEQ ID NOS: 45, 46, 47, 53, 54, and 57 for CRISPR editing in a biologically acceptable carrier.” The structure(s) required of this limitation is unclear. It is not clear if the limitation requires, for example, I) a guide strand comprising one or more of the recited sequences with the intended use of CRISPR editing in a biologically acceptable carrier, II) a guide strand in a biologically acceptable carrier, for the intended use of CRISPR editing, wherein the guide strand comprises one or more of the recited sequences, or III) one or more guide strands in a biologically acceptable carrier, for the intended use of CRISPR editing, wherein each guide strand is selected from one of the recited SEQ ID NOs, or some combination of the aforementioned interpretations.
Claims 17, and 19-22 are rejected for depending from claim 16 and failing to remedy the indefiniteness. In the interest of compact prosecution, the claims will be interpreted hereinafter as in interpretation (III) above.
Claim 21 recites “Human stem cells comprising the composition of claim 20, said stem cells being suitable for transplantation into a recipient suffering from a ribosomopathy.” It is not clear what structure(s) are required of the human stem cells such that they would be suitable for transplantation into a recipient suffering from a ribosomopathy. For example, it is not clear whether any human stem cell is suitable for administration into such a recipient, or whether the human stem cells must comprise specific structure(s) and/or characteristics, e.g., specific gene(s) or variants thereof, expression of certain factors, at particular levels, etc., to be suitable for administration into such a recipient. The scope of human stem cells encompassed by the claim are unclear.
Claim 22 is rejected for depending from claim 21 and failing to remedy the indefiniteness. In the interest of compact prosecution, any human stem cell will be interpreted as meeting the scope of the claim.
Claim 22 recites “wherein said stem cells are… obtained from an immunologically compatible donor.” This is a product-by-process limitation, wherein the stem cells are a product obtained from an immunologically compatible donor. It is not clear which donors would be considered “immunologically compatible,” because there is no definition provided in the specification for this term, and no metrics to ascertain the donors which would be “immunologically compatible.” Furthermore, there does not appear to be an accepted standard in the art for the term, and what would be “immunologically compatible” in one context, may not be “immunologically compatible” in another context. Because the donors from which the stem cells may be obtained are unclear, the structure of the stem cells encompassed by the claim are unclear.
In the interest of compact prosecution, the claim will be interpreted as encompassing autologous human stem cells, and human stem cells obtained from any donor.
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 21 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 drawn to “Human stem cells.” The specification does not provide a limiting definition of a human stem cell, and does not expressly exclude cells within a human organism (“Viral vectors can be administered directly to patients (in vivo),” pg. 32, lines 3-4; “a cell is transfected as it naturally occurs in a subject… the cell is a human stem cell… in a eukaryotic cell, which may be in vivo,” pg. 33, lines 20-26. The term “Human stem cell” could reasonably be interpreted as encompassing cells within a human organism, which is non-statutory subject matter.
Claim Rejections - 35 USC § 102 – Khvorova
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 16-17, and 19-20 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Khvorova (Khvorova et al., US 2019/0345573 A1, published 14 November 2019).
Regarding claim 16, Khvorova teaches a composition comprising a synthetic nucleic acid molecule, wherein the synthetic nucleic acid molecule is an siRNA comprising a sequence 100% identical to instant SEQ ID NO: 51 (“42. An RNA molecule capable of inducing the RNA interference pathway, wherein… said antisense region comprises a sequence that is the complement of a sequence selected from the group comprised of SEQ ID NO: 1 to 2675299,” pg. 79; “the siRNA… is applied to a cell through transfection… include the use of lipid-based carriers… through vectors… conjugations to other molecules… formulating in a physiological acceptable solution,” [0413]). See attached alignment in Appendix I between instant SEQ ID NO: 51 and Khvorova SEQ ID NO: 2415457, which corresponds to the sense strand of the siRNA.
Khvorova’s siRNA comprises the same structure as the instantly recited siRNA. The ZNF622 expression reducing and hybridizing, and symptom ameliorating functions recited in the claim are presumed to be inherent to Khvorova’s siRNA. See MPEP 2112.01. Indeed, as shown in the attached alignment in Appendix I, Khvorova’s siRNA targets (i.e., hybridizes with) the ZNF622 mRNA set forth in SEQ ID NO: 36. In addition, Khvorova’s siRNA comprises a substantially identical structure to an siRNA in the specification which inhibits expression of the ZNF622 mRNA set forth in SEQ ID NO: 36 (see Fig. 15A). The specification teaches that inhibiting expression of ZNF622 is effective to ameliorate symptoms of at least one of hereditary anemia, myelodysplastic syndrome or severe chronic hemolysis, wherein the symptoms are hematopoietic stem cell defects (see pg. 3, line 5 to pg. 4, line 26; Examples I-II).
Regarding claim 17, Khvorova teaches modifications which increase stability in bodily fluids and/or uptake in a cell of interest ([0410]; [0413]). For the reasons described above, the SEQ ID NO: 36 inhibiting and targeting functions recited in the claim are presumed to be inherent to Khvorova’s siRNA. See MPEP 2112.01.
Regarding claim 19, Khvorova teaches a vector comprising the synthetic nucleic acid molecule ([0413]).
Regarding claim 20, the specification does not structurally limit the formulations which are suitable for ex vivo cellular administration, parenteral administration, and intravenous administration. As such, the claim is interpreted as being drawn to any composition suitable for administration to a subject, i.e., a pharmacologically or physiologically acceptable formulation. Khvorova teaches formulations which are physiologically acceptable, and therefore, would be considered suitable for ex vivo cellular administration, parenteral administration, and intravenous administration ([0413]).
Notice to Joint Inventors
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.
Claim Rejections - 35 USC § 103 – Khvorova in view of CHOP
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.
Claims 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Khvorova (Khvorova et al., US 2019/0345573 A1, published 14 November 2019) as applied to claims 16-17, and 19-20, in view of CHOP (“CHOP Researchers Find Ribosome Assembly Essential for Stem Cell Regeneration,” 10 March 2021, Children’s Hospital of Philadelphia, https://www.chop.edu/news/chop-researchers-find-ribosome-assembly-essential-stem-cell-regeneration).
The teachings of Khvorova are described above and applied hereinafter with respect to claims 16-17, and 19-20. Khvorova also teaches human cells comprising the synthetic nucleic acid molecule (pg. 80, claims 47-48). Khvorova teaches means to introduce compositions comprising a synthetic nucleic acid molecule into cells relevant to the targeted RNA (“Example XVII: Gene Silencing: Prophetic Example… Select a cell line. The selection of a cell line is usually determined by the directed application. The most important feature to RNAi is the level of expression of the gene of interest,” [0553]-[0561]).
Regarding claim 21, Khvorova does not teach human stem cells comprising the composition comprising the synthetic nucleic acid molecule.
However, CHOP teaches that ZNF622 is a relevant target RNA for human hematopoietic stem cells (“identified genes responsible for hematopoietic stem cell (HSC) regeneration,” “knocking out the Znf622 gene in Hectd1-deficient HSCs… leading to restored protein synthesis and HSC production”). CHOP suggests knocking down ZNF622 in human hematopoietic stem cells for therapeutic purposes in patients with bone marrow failure (“knocking down Znf622 to restore proper bone marrow function, which is critical for child development,” “Future research should look at this mechanism as a potential target for patients with these disorders”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have prepared human hematopoietic stem cells comprising the composition comprising the synthetic nucleic acid molecule of Khvorova in view of CHOP. It would have amounted to introducing a known composition comprising a known synthetic nucleic acid molecule, into a cell type relevant for the target RNA, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the human hematopoietic stem cells because means of introducing compositions comprising a synthetic nucleic acid molecule into human cells and human hematopoietic stem cells were well known based on Khvorova and CHOP. The skilled artisan would have recognized that the target RNA of the synthetic nucleic acid molecule of Khvorova was relevant to human hematopoietic stem cells based on CHOP. CHOP also explicitly suggests knocking down ZNF622 in human hematopoietic stem cells. The skilled artisan, therefore, would have been motivated to prepare human hematopoietic stem cells comprising the composition comprising the synthetic nucleic acid molecule.
Regarding claim 22, CHOP does not explicitly teach autologous human stem cells or human stem cells obtained from a donor.
However, as described above, CHOP suggests knocking down ZNF622 in human hematopoietic stem cells for therapeutic purposes in patients with bone marrow failure (“knocking down Znf622 to restore proper bone marrow function, which is critical for child development,” “Future research should look at this mechanism as a potential target for patients with these disorders”). To “restore proper bone marrow function” using ZNF622 knockdown, the skilled artisan would at once envisage the three means to knockdown ZNF622 in human hematopoietic stem cells for therapeutic purposes: in vivo, ex vivo (i.e., autologous), and in donor-derived cells. Thus, although CHOP does not expressly spell out the limitations recited in instant claim 22, the skilled artisan, reading CHOP would at once envisage the means to “restore proper bone marrow function” using ZNF622 knockdown.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have prepared donor-derived or autologous human hematopoietic stem cells comprising the composition comprising the synthetic nucleic acid molecule of Khvorova in view of CHOP. It would have amounted to introducing a known composition comprising a known synthetic nucleic acid molecule, into a cell type relevant for the target RNA, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the donor-derived or autologous human hematopoietic stem cells because means of introducing compositions comprising a synthetic nucleic acid molecule into human cells and human hematopoietic stem cells were well known based on Khvorova and CHOP. CHOP explicitly suggests knocking down ZNF622 in human hematopoietic stem cells for the purposes of restoring bone marrow function in patients with bone marrow failure. The skilled artisan reading CHOP would at once envisage that there are three means to “restore proper bone marrow function” using ZNF622 knockdown, and in an effort to develop such therapies, would have been motivated to prepare donor-derived or autologous human hematopoietic stem cells comprising the composition comprising the synthetic nucleic acid molecule.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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, JENNIFER A DUNSTON can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
