DETAILED ACTION
Receipt of Arguments/Remarks filed on March 18 2026 is acknowledged. Claims 5, 7-9, 16 and 18-19 were/stand cancelled. Claims 1, 6, 10, 12 and 17 were amended. Claims 23-24 were added. Claims 1-4, 6, 10-17 and 20-24 are pending.
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 .
Withdrawn Objections/Rejections
The amendments filed March 18 2026 are sufficient to overcome the objections to the drawings. The different view for Figure 4 are now all accompanied by a letter and not Cont.
The amendments filed March 18 2026 are sufficient to overcome the rejection of claims 1-6, 9-17 and 20-22 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The claims now recite a specific sequence corresponding to the inhibitor.
The amendments filed March 18 2026 are sufficient to overcome the rejection of claims 12-17 and 20-22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Claim 12 was amended to recite ZNF410 inhibitor which also corrects the antecedent basis issues in claims 16 and 22.
The amendments filed March 18 2026 are sufficient to overcome the rejection of claims 1-6 and 9 under 35 U.S.C. 102(a)(1) by Chen et al. (Journal of Cellular Physiology, 2018) as evidenced by Wang et al. (Oncology Letters, 2018). The claims now recite SEQ ID NO: 5 or its complement which is not suggested by Chen et al.
New and modified Rejections Necessitated by the
Amendments filed March 18 2026
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 6, 17 and 23-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claims 6, 17 and 23-24 introduce new matter as the claims recite the limitation: "wherein said inhibitor nucleic acid molecule is an siRNA or shRNA or an antisense molecule”. These claims depend from claims 1 and 12 which as amended recite at least one ZNF410 inhibitor is an inhibitory nucleic acid molecule and comprises SEQ ID NO: 5 or the complement of SEQ ID NO:5. Looking to the instant specification, page 23 SEQ ID NO: 5 is an sgRNA. Page 11 teaches that the guide RNA is a single molecule (sgRNA) which comprises a sequence which specifically hybridizes with a target sequence (page 12). There is no support in the specification for SEQ ID NO: 5 or the complement of SEQ ID NO: 5 being an siRNA, shRNA or an antisense oligonucleotide. The limitation of: SEQ ID NO:5 being an siRNA, shRNA or antisense oligonucleotide was not described in the specification as filed, and person skilled in the art would not recognize in the applicant’s disclosure a description of the invention as presently claimed. While the specification discloses inhibitory nucleic acids include siRNA, shRNA and antisense oligonucleotides, the instant claims require SEQ ID NO: 5, which is only taught as an sgRNA, to be an siRNA, shRNA or antisense oligonucleotide and thus does not teach the claimed limitations. There is no guidance in the specification to select SEQ ID NO: 5 as the siRNA, shRNA or antisense oligonucleotide and from MPEP 2163.06: “Applicant should therefore specifically point out the support for any amendments made to the disclosure.” Applicant has not directed the Examiner to the support in the specification for the amendments. Therefore, it is the Examiner’s position that the disclosure does not reasonably convey that the inventor had possession of the subject matter of the amendment at the time of filing of the instant application.
Claim Rejections - 35 USC § 102
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)(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.
Claim(s) 1-4 and 12-15 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bauer et al. (USPGPUB No. 20230257746, effective filing date is July 17 2020).
The instant application claims a method of increasing the level of human fetal hemoglobin and/or y-globin in subject, the method comprising administering at least one zinc finger protein 410 (ZNF410) inhibitor to the subject, wherein said ZNF410 inhibitor is an inhibitor nucleic acid molecule and comprises SEQ ID NO: 5 or the complement of SEQ ID No: 5.
The instant application claims a method of treating a hemoglobinopathy in a subject in need thereof, the method comprising administering a composition comprising at least one zinc finger protein 410 (ZNF410) inhibitor and a pharmaceutically acceptable carrier to the subject, wherein said ZNF410 inhibitor is an inhibitor nucleic acid molecule and comprises SEQ ID No: 5 or the complement of SEQ ID NO: 5.
Bauer et al. claims a method of increasing fetal hemoglobin level in a subject, the method comprising: administering to a subject in need thereof an agent that decreases the level or activity of zinc finger 410 (ZNF410) (claim 1) (i.e. a ZNF410 inhibitor). The subject has a hemoglobinopathy (claim 2; 3). As claimed the agent is a nucleic acid comprising a nucleotide sequence selected from SEQ ID NO: 1-189 (claim 6) or SEQ ID No: 1-SEQ ID NO: 169 (claim 7).
As shown below SEQ ID NO: 5 (Qy) has 100% identity to SEQ ID NO: 85 (Db) of Bauer et al.
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Regarding claims 1 and 12, where selection of one named species from a list of alternatives is all that is required to arrive at the instantly claimed subject matter, that species is anticipated. Ex Parte A., 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). See also In re Sivaramakrishnan, 213 USPQ 441 (CCPA 1982). MPEP 2131.02. Bauer et al. expressly claims the same patient population (i.e. patient with hemoglobinopathy) and administering a ZNF410 inhibitor. In order to arrive at the instantly claimed invention, all one would have to do is select SEQ ID No: 85 from the finite list of agents recited in claim 7 of Bauer et al.
Regarding claims 2-4 and 13-15, Bauer et al. claims the subject has a hemoglobinopathy (claim 2) and the hemoglobinopathy is β-hemoglobinopathy (claim 12), sickle cell or thalassemia (claim 13).
The examiner notes that provisional 63/053308 provides support for increasing fetal hemoglobin level in a subject, treating a hemoglobinopathy in a subject and SEQ ID No: 85 (page 16).
The examiner is of the position that the claims of Bauer et al. anticipate the elected species. In the event the elected species is not deemed to be anticipated, the claims are obvious for the reasons set forth below.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 9, 12-15 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Bauer et al. (USPGPUB No. 20230257746, effective filing date is July 17 2020).
Applicant Claims
The instant application claims a method of increasing the level of human fetal hemoglobin and/or y-globin in subject, the method comprising administering at least one zinc finger protein 410 (ZNF410) inhibitor to the subject, wherein said ZNF410 inhibitor is an inhibitor nucleic acid molecule and comprises SEQ ID NO: 5 or the complement of SEQ ID No: 5.
The instant application claims a method of treating a hemoglobinopathy in a subject in need thereof, the method comprising administering a composition comprising at least one zinc finger protein 410 (ZNF410) inhibitor and a pharmaceutically acceptable carrier to the subject, wherein said ZNF410 inhibitor is an inhibitor nucleic acid molecule and comprises SEQ ID No: 5 or the complement of SEQ ID NO: 5.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Bauer et al. claims a method of increasing fetal hemoglobin level in a subject, the method comprising: administering to a subject in need thereof an agent that decreases the level or activity of zinc finger 410 (ZNF410) (claim 1). The subject has a hemoglobinopathy (claim 2; 3). As claimed the agent is a nucleic acid comprising a nucleotide sequence selected from SEQ ID No: 1-SEQ ID NO: 169 (claim 7).
As shown below SEQ ID NO: 5 (Qy) has 100% identity to SEQ ID NO: 85 (Db) of Bauer et al.
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Bauer et al. teaches that other aspects of the invention include a method of transplanting a cell that has been contacted with a gene editing composition. Specifically it is contemplated that hematopoietic stem cells can be edited to reduce the levels of ZNF410 and increase the expression of HbF. The edited cells can be xenotransplanted into the subject (paragraph 0105). Claimed is a synthetic nucleic acid molecule comprising a nucleotide sequence selected from SEQ ID NO: 1-183 (claim 16). A composition comprising the synthetic nucleic acid molecule and a nuclease enzyme (claims 28-29). The nucleic acid agent is a guide RNA, a sgRNA, an siRNA, a shRNA, an antisense oligonucleotide, etc. (paragraph 0040; claim 5).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Bauer et al. does not exemplify SEQ ID NO: 85 in the claimed method or in a stem cell.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 1 and 12, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to selected SEQ ID No: 85 from the list of agents recited in Bauer et al. It would have been obvious to one of ordinary skill in the art to try any of the specifically claim agents, i.e. the specifically recited nucleotide sequences, as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
Regarding claims 2-4 and 13-15, Bauer et al. claims the subject has a hemoglobinpathy (claim 2) and the hemoglobinpathy is β-hemoglobinopathy (claim 12), sickle cell or thalassemia (claim 13).
Regarding claims 9 and 22, Bauer et al. teaches that other aspects of the invention include a method of transplanting a cell that has been contacted with a gene editing composition. Specifically it is contemplated that hematopoietic stem cells can be edited to reduce the levels of ZNF410 and increase the expression of HbF. The edited cells can be xenotransplanted into the subject. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize any of the nucleic acid agents including the nucleic acid of SEQ ID No: 85 in combination with a nuclease enzyme and administer to a stem cell in order to reduce the levels of ZNF410 and then xenotransplant the edited cell into the subject. Since Bauer et al. expressly a composition comprising the nucleotide sequence and nuclease enzyme there is a reasonable expectation of success.
Claims 10-11 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Bauer et al. as applied to claims 1-4, 9, 12-15 and 22 above in view of Lowrey (Blood, 2016).
Applicant Claims
The instant application claims the method further comprising administering at least one fetal hemoglobin inducer to the cell or subject.
The inducer is pomalidomide.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Bauer et al. are set forth above. Bauer et al. teaches treating hemoglobinopathy and administering a ZNF410 inhibitor to patients with thalassemia and sickle cell.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Bauer et al. does not teach the use of pomalidomide. However, this deficiency is cured by Lowrey.
Lowrey teaches that one of the major goals of hemoglobinopathy research has been to devise improved pharmacologic strategies for the induction of fetal hemoglobin (HbF) in people with sickle cell disease and β-thalassemia. Pomalidomide induces HbF production by decreasing levels of several key transcription repressors of fetal globin gene expression. Pomalidomide induces HbF in differentiating erythroid cells from people with sickle cell disease (page 1364). Shown is the induction of HbF by pomalidomide. The suppression is noted at both the RNA and protein levels and is most pronounced early in differentiation. This leads to increased levels of HbF and decreased levels of adjust hemoglobin in mature erythrocytes (page 1385, figure at end).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bauer et al. and Lowrey and utilize pomalidomide in combination with the ZNF410 inhibitor of Bauer et al. One skilled in the art would have been motivated to use pomalidomide as it has been shown to induce fetal hemoglobin in people with sickle cell disease and β-thalassemia as taught by Lowrey. There is a reasonable expectation as both Bauer et al. and Lowrey teach increase hemoglobin in the same patient population. As a general principle it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose, the idea of combining them flows logically from their having been individually taught in the prior art. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06.
Response to Arguments
Applicants’ arguments filed March 18 2026 have been fully considered but they are not persuasive.
Applicants argue that the claims have been amended to recite that the ZNF410 is an inhibitor nucleic acid molecule which comprises SEQ ID NO: 5 or the complement of SEQ ID No: 5. It is noted that Bauer et al. claims priority to US 63053308, filed July 17 2020 but the other provisional cited by Bauer et al. and the PCT application were filed after the earliest priority date of the instant application. The examiner alleges the provisional provides support for increasing fetal hemoglobin level in a subject, treating a hemoglobinopathy and SEQ ID NO: 85 but applicants disagree. The ’308 application fails to teach administration of an inhibitor to a subject to increase fetal hemoglobin levels or for treating a hemoglobinopathy. Application ‘308 never teaches administration to a subject nor any therapeutic effect. Application ‘308 fails to demonstrate the effectiveness of any gRNA. The data in table 1 was obtained by administering a gRNA library to cells then an HbF enrichment score was determined. Thus the HbF enrichment score relates to how frequently the gRNA is found but this does not mean that the specific gRNA is responsible for the increase. Application ‘308 provides 183 possible gRNA but fails to teach which are effective inhibitors. The skilled artisan is left with impermissible random picking and choosing. It is argued that SEQ ID NO: 85 only has a enrichment score which is near the middle of the RNA tested. SEQ ID NO: 4 of the instant application approximates to SEQ ID NO: 37 of Application ‘308. SEQ ID NO: 37 is taught to have a superior HbF enrichment score. This is in contrast to the instant application which shows that SEQ ID NO: 5 increases HbF to the same or high levels than SEQ ID NO: 4. Based on the score in the ‘308 application this is an unexpected finding.
Regarding Applicants arguments, firstly, the examiner agrees that the other provisional application and the PCT application are filed later than applicants oldest provisional priority claim. However, the examiner cannot agree that the ‘308 application does not provide support for the claims in Baur et al. establishing that Bauer was earlier filed. Looking to Bauer et al., specifically page 16, the second to last entry corresponds to SEQ ID NO:85 which corresponds to instantly claimed SEQ ID NO: 5. Bauer et al. makes it clear that all the compounds taught in Table 1 are gRNAs wherein positive scores indicate HbF induction and a positive fitness score indicates a fitness advantage (pages 5-6). Page 25 makes it clear that the sgRNA were electroporation in cells followed by infusion to immunodeficient mice (i.e. subject) see also Fig. 6.. Fig. 1 makes it clear that ZNF410 is a repressor of fetal hemoglobin expression. Thus, Application ‘308 clearly provides support for the claims as set forth in Bauer et al. Regarding the arguments with regards to not teaching any activity, the examiner cannot agree. Table 1 makes it clear that positive enrichment scores indicate HbF induction and that positive fitness scores indicate fitness advantage. Pages 5-6 make it clear it is for each gRNA. Since the sequence corresponding to SEQ ID NO: 5 possess both a positive enrichment score and a positive fitness score, there is clear motivation to select this particular sequence. While there might be other equally obvious sequences, this does not negate that SEQ ID NO: 85 is a suitable option. “Disclosure of a multitude of effective combinations does not render any particular formulation less obvious.” Merck & Co. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). It is not necessary to show that a combination is the best option, only that it be a suitable option. Note: MPEP 2144.07.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here the only selection required to arrive at the claimed invention is select SEQ ID NO: 85. As set forth above, Bauer et al. makes it clear positive fitness score and positive enrichment score are what is desired. SEQ ID NO: 85 possesses both. With regards to the claimed invention, the literal title of the ‘308 application is targeting ZNF410 for fetal hemoglobin induction in beta-hemoglobinopathies. Therefore, the examiner cannot agree that to arrive at the instant claims hindsight must be utilized.
Regarding Applicants’ arguments with regards to the purported unexpected results. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. An unexpected property or result must actually be unexpected and of statistical and practical significance. The burden is on the applicant to establish the results are in fact unexpected, unobvious and of statistical and practical significance. See MPEP 716.02. Applicants argue that based on the values in the Table in the ‘308 application there is an expectation that SEQ ID NO: 37 which corresponds to SEQ ID NO: 4 would perform better but Applicants found SEQ ID NO: 5 performed better. But the examiner cannot agree that this is actually true. While there is a difference, 14% for SEQ ID NO: 5 vs. 11% for SEQ ID NO: 4, nothing in the data establishes this is of a statistical and practical significance. Furthermore, the examiner cannot agree that the expectation is that SEQ ID NO: 37 would perform better than SEQ ID NO: 85 in Bauer et al. Nothing in Bauer et al. indicates that a higher score is better merely that a positive score indicates HbF induction or fitness advantage.
Therefore, the rejections are maintained as Applicants have not demonstrated an unexpected effect with the claimed sequence. The examiner is of the position that based on the teachings of Bauer et al., one skilled in the art would have selected any of SEQ ID NO; 1-183 with the expectation that any of these sequences could be utilized to decrease the level or activity of ZNF410.
Conclusion
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 ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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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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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636
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