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 amendments filed 13 January 2026 and supplemental amendments and remarks filed 14 January 2026. The supplemental amendments have been considered and entered into the case.
Claim Objections
Claims 2-5, 8-10, 13, 18-19, are objected to because of the following informalities:
The replies filed on 13 January 2026 and 14 January 2026, are not in proper form because of the following matter(s): the claims are not considered to be in compliance with 37 CFR § 1.121, recited here:
§ 1.121(c) Manner of making amendments in applications.
Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of "canceled" or "not entered" may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(c)(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn— currently amended.”
The claim amendment submitted 13 January 2026 amended claims 2-3, 5, 8-10, 13, 18-19, and 22-23 to depend from “claim 0”. These claims did not have proper markings to indicate the changes and the status indicators were not changed to “Currently Amended”. The supplemental amendment submitted 14 January 2026 changed the dependencies of the same claims back to “claim 1”. These claims did not have proper markings to indicate the changes and the status indicators were not changed to “Currently Amended” to indicate the changes from the 13 January 2026 claim set. Both claim sets also contain several claims with the status of “Original” when it should be “Previously Presented”.
While it would be appropriate to reject entry of the present amendment for noncompliance with 37 CFR § 1.121, applicant is instead respectfully reminded to properly note the status of each claim submitted in order to avoid the issuance of a Notice of Non-Compliant Amendment, which would delay prosecution and potentially have an adverse effect on any patent term adjustment should the claims proceed to issue.
Appropriate correction is required.
Election/Restrictions
Claims 22-23 and 26-27 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. Election was made without traverse in the reply filed on 23 September 2025.
Applicant added new claims 29-33, in the amendments filed 14 January 2026, which ultimately depend from claim 1. Therefore, these claims have been added to the previously elected group 1. Group 1 now comprises claims 1-6, 8-11, 13, 15-16, 18-19, 21, and 29-33.
Applicant added new claim 34, in the amendments filed 14 January 2026, which depends from withdrawn claim 26, therefore, claim 34 is 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.
Claim Status
Claims 7, 12, 14, 17, 20, 24-25, and 28 were previously canceled, claims 1 and 5 are currently amended, claims 29-34 are new, claims 22-23, 26-27, and 34 are withdrawn as being drawn to a nonelected invention, and claims 1-6, 8-11, 13, 15-16, 18-19, 21, and 29-33 have been considered on their merits.
Withdrawn Rejections
The claim rejection under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendments to the claims.
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.
Claims 1-3, 5-6, 8-11, 13, 15-16, 18-19, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ryu et al. (WO2018/009506, published 11 January 2018, of record).
This rejection is repeated with regard to claims 1-3, 5-6, 8-11, 13, 15-16, 18-19, and 21 for the same reasons of record as set forth in the Official action mailed 16 October 2025. A response to applicant' s traversal follows the reiterated rejection below.
Regarding claims 1 and 2, Ryu et al. teach a human GATA-1 erythroid specific enhancer (claim 2) sequence which is contained in a DNA construct (Abstract). Ryu et al. teach the disclosed DNA construct can be a cloning vector, expression vector, or expression cassette (para. [0009]). Ryu et al. teach SEQ ID NO: 4 (para. [0020]) which has a query match of 57.1% to instant SEQ ID NO: 6, the details can be found in the search results from 02 October 2025, file us-17-793-793-6.rng, Result 12, accession number: BET87033. See alignment below:
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Regarding claims 3 and 5, Ryu et al. teach erythroid-specific enhancers BCL11A +58 enhancer, GATA-1 enhancer (SEQ ID NO: 4), and HS40 enhancer, in two different orientations, were analyzed in combination with the glycophorin A promoter or Ankyrin promoter (para. [0018]). Ryu et al. teach this analysis indicated human GATA1 enhancer and BCL11A +58 erythroid specific enhancer provided the best enhancement of expression (para. [0018]). The human GATA1 enhancer and BCL11A +58 erythroid specific enhancer read as the cassette comprises multiple copies of the enhancer element (claim 3) and a first enhancer element and a second enhancer element have different sequences (claim 5).
Regarding claims 6 and 8-9, Ryu et al. teach the nucleotide coding sequence of interest is a nucleotide encoding a polypeptide which provides a therapeutic function (claim 6) for the treatment of a hemoglobinopathy (para. [0024]). Ryu et al. teach the nucleotide sequence coding the sequence of interest encodes a globin gene, such as α-globin, β-globin, γ-globin, or δ-globin (claims 8 and 9) (para. [0024]).
Regarding claim 10, Ryu et al. teach utilization of an erythroid-specific enhancer in combination with the glycophorin A promoter (a human erythroid promoter) to increase promoter strength without affecting lineage expression (para. [0018]). Ryu et al. teach the expression vector includes the erythroid lineage-specific promoter from glycophorin A operably linked to the nucleotide coding sequence of interest (para. [0011]).
Regarding claim 11, Ryu et al. teach the gene therapy vector is a retroviral vector or a lentiviral vector, since lentiviral vectors are capable of providing efficient delivery, integration and long-term expression of transgenes into non-dividing cels both in vitro and in vivo (para. [0031]).
Regarding claim 13, Ryu et al. teach erythroid-specific enhancers BCL11A +58 enhancer (a first enhancer element), GATA-1 enhancer (a second enhancer element) and HS40 enhancer, in two different orientations, were analyzed in combination with the glycophorin A promoter (a promoter) or Ankyrin promoter (para. [0018]). Ryu et al. teach the expression vector includes the erythroid lineage-specific promoter from glycophorin A operably linked to the nucleotide coding sequence of interest (para. [0011]). Ryu et al. teach the nucleotide coding sequence of interest is a nucleotide encoding a polypeptide that provides a therapeutic function for the treatment of a hemoglobinopathy (a therapeutic gene) (para. [0024]). Additionally, Ryu et al. teach the expression cassette may further include other DNA sequences, such as enhancers, UTRs, Kozak sequences, polyadenylation signals, additional restriction enzyme sites, and multiple cloning sites (para. [0011]).
Regarding claim 15, Ryu et al. teach lentiviral vectors comprising a CMV promoter
(Fig. 1 and para. [0006]).
Regarding claims 16 and 18-19, Ryu et al. teach cell suitable for transduction and administration in the gene therapy methods include hematopoietic stem cells (HSCs) (claims 16 and 18) (para. [0047]). Ryu et al. teach the HSCs may be identified according to certain phenotypic or genotypic markers and the presence of various antigenic markers on their surface, many of which belong to the cluster of differentiation series, such as CD34 (para. [0051]). This reads as the hematopoietic stem cell is a CD34+ hematopoietic stem cell (claim 19).
Regarding claim 21, Ryu et al. teach the formulations or compositions disclosed are suitable for the delivery of viral vector including retroviral vectors (para. [0042]). Ryu et al. teach methods for preventing or treating a hematopoietic disorder by administering to a subject in need of treatment an effective amount of the disclosed DNA construct or viral vector (para. [0042], pp. 23-24). This reads as a pharmaceutical composition.
Thus, the reference anticipates the subject matter of claims 1-3, 5-6, 8-11, 13, 15-16, 18-19, and 21.
Response to Traversal
Applicant's arguments filed 14 January 2026 have been fully considered but they are not persuasive. The claims as amended still comprise SEQ ID NO: 6, therefore, the rejection has been maintained.
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.
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 1-6, 8-11, 13, 15-16, 18-19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Ryu et al. (WO2018/009506, published 11 January 2018, of record) as applied to claims 1-3, 5-6, 8-11, 13, 15-16, 18-19, and 21 above.
This rejection is repeated with regard to claim 4 for the same reasons of record as set forth in the Official action mailed 16 October 2025. A response to applicant' s traversal follows the reiterated rejection below.
Ryu et al. anticipate the subject matter of claims 1-3, 5-6, 8-11, 13, 15-16, 18-19, and 21, and thus, also render them obvious. One of ordinary skill would have been motivated with a reasonable expectation of success to carry out the claimed invention because Ryan teach and suggest all the claim limitations as described above.
Regarding claim 4, Ryu et al. teach multiple enhancer elements in the same expression cassette, however, Ryu et al. is silent to the expression cassette comprising two copies of the same enhancer element.
However, it would have been obvious to one of ordinary skill in the art to utilize two copies of the same enhancer elements of Ryu et al. with a reasonable expectation of success because Ryu et al. teach the disclosed DNA construct can include one or a combination of erythroid-specific enhancers in combination with the glycophorin A promoter (para. [0018]). A person of ordinary skilled in the art would have been motivated to utilize two copies of the same enhancer elements because MPEP § 2144.06(II) states, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Therefore, it would have been obvious to utilize two copies of the same enhancer elements of Ryu et al. because multiple copies of the same enhancer element has the potential to provide an additive or synergistic effect which could increase protein expression. Additionally, multiple copies of the same enhancer element would increase the number of binding sites for erythroid-specific transcription factors, such as GATA1, which are required for proper globin expression.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claims 29-33 are rejected under 35 U.S.C. 103 as being unpatentable over Ryu et al. (WO2018/009506, published 11 January 2018, of record) as applied to claims 1-6, 8-11, 13, 15-16, 18-19, and 21 above, and further in view of Gallagher et al. (J Biol Chem 274 (10), 1999).
This is a new rejection, necessitated by applicant’s amendments to the claims.
Ryu et al. anticipate the subject matter of claims 1-3, 5-6, 8-11, 13, 15-16, 18-19, and 21, and thus, also render them obvious. One of ordinary skill would have been motivated with a reasonable expectation of success to carry out the claimed invention because Ryan teach and suggest all the claim limitations as described above.
Regarding claim 29, Ryu et al. do not teach wherein the nucleotide sequence at least 90% identical to any one of SEQ ID NO: 1-5 and 6-10.
Regarding claims 30-31, Ryu et al. do not teach wherein the nucleotide sequence is at least 95% (claim 30) or 100% (claim 31) identical to the nucleotide sequences in any one of SEQ ID NO: 1-3.
However, Gallagher et al. teach the 5’ end of the β-spectrin erythroid cDNA and cloned the 5’-flanking genomic DNA containing the putative β-spectrin gene promoter (Abstract). Gallagher et al. teach identification of a β-spectrin gene erythroid promoter with two binding sites for GATA-1 and one site for CACCC-related proteins, wherein all three binding sites were required for full promoter activity (Abstract). Gallagher et al. teach the β-spectrin gene promoter was able to be transactivated in heterologous cells by forced expression of GATA-1 (Abstract). Gallagher et al. teach Sp1 and EKLF have both been shown to physically interact with GATA-1 in the regulatory elements of certain erythroid genes to synergistically activate transcription in transfected cells (p. 6072, 1st column). KLF1 is an alternative identifier for EKLF. Gallagher et al. teach a promoter-reporter plasmid for transgenic mice, the plasmid comprising the coding region of the human γ-globin gene (p. 6065, 2nd column). Gallagher et al. teach a promoter-reporter plasmid for transgenic mice, the plasmid comprising human β-spectrin promoter fragment (p. 6065, 2nd column). Gallagher et al. teach transient transfection of the plasmid into erythroid cells (p. 6066, 1st column). Gallagher et al. teach a sequence with 100% identity to instant SEQ ID NO: 2, see alignment below:
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Therefore, it would have been obvious to one of ordinary skill in the art to substitute the sequence of Gallagher et al. in the expression cassette of Ryu et al. because both Gallagher et al. and Ryu et al. teach an expression cassette comprising a human GATA-1 erythroid specific enhancer. Substitution of one known element for another known element, the elements having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP 2143(I).
Regarding claim 32, Ryu et al. in view of Gallagher et al. are silent to the cell specifically being an induced pluripotent stem cell (iPSC).
However, Ryu et al. teach the use of stem cells is preferred because they have the ability to differentiate into the appropriate cell types with administered to a particular biological niche (para. [0048]). Ryu et al. teach pluripotent stem cells have the ability to form all lineages of the body or soma, which would include the ability to form HSCs (para. [0049]). As such, Ryu et al. suggest the use of pluripotent stem cells.
Therefore, it would have been obvious to one of ordinary skill in the art to utilize an iPSC with a reasonable expectation of success because substitution of one known element for another known element, the elements having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP 2143(I). Since iPSCs and PSCs would be equally capable of comprising an expression cassette as they are both capable and regularly utilized for transgenic expression.
Regarding claim 33, Ryu et al. teach cell suitable for transduction and administration in the gene therapy methods include hematopoietic stem cells (HSCs) (para. [0047]).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
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.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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