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 office action is in response to the paper filed on 03/11/2026. Claims 1-5, 27, 34, 43, 54-55, 73, 75-77, 80-81, 83, 87-88, and 90 were previously presented, claims 94-99 are newly presented.
Election/Restriction
Applicant’s election of invention of Group I (claims 1-5, 27, 34, 43, 54, 55, 73, and 75-77), in the reply filed on 03/11/2026, is acknowledged. Claims 94-99 are newly added and applies to the invention of Group I.
Applicant elects the inventions of Group I, a method for delivering an oligonucleotide conjugate to an eye of a subject, (claims 1-5, 27, 34, 43, 54, 55, 73, 75-77, and 94-99) and the following species: a) where the oligonucleotide comprises of an siRNA and b) and wherein the functional moiety linked to an oligonucleotide is docosanoic acid (DCA), without traverse.
Claims 80, 81, 83, 87, 88, and 90 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant is reminded that upon the cancelation of claim to non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Application Status
This action is written in response to applicant’s correspondence received on 03/11/2026. Claims 1-5, 27, 34, 43, 54, 55, 73, 75-77, and 94-99 are pending in the instant application and currently under examination on the merits.
Priority
This application claims priority to provisional application 63/412,051 with an effective filing date of 09/30/2022.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of colored drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color (Fig. 1-6, 9, 11, 13-16, 19, 21-25, 27-29). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. In the case of the instant application, the supplemental drawings filed on 09/29/2023 contain colored figures.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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.
(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.
Claim(s) 1, 2, 3, 4, 5, 34, 43, 54, 55, 73, 75, 94, 95, 96, 97, 98, and 99 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khvorova et al. (US 2021/0115442 A1, 04/22/2021).
Regarding all claims, Khvorova teaches wherein the disclosure provides a method of treating or managing a disease or disorder comprising administering to a subject, in need of such treatment or management, a therapeutically effective amount of the pharmaceutical composition above (see paragraph 0035) and where an RNA silencing agent of the disclosure can be administered ocularly, such as to treat retinal disorders (see paragraph 0431).
Regarding claim 1, Khvorova teaches a chemically-modified oligonucleotides, (see paragraph 0006), wherein the oligonucleotide comprises perfect or less than perfect complementary to a target (see paragraph 0009). Khvorova teaches that the 5’ or 3’ end of the oligonucleotide comprises of a non-2’-O-methyl modification or a moiety (see paragraph 0011 and 0012) and further teaches, where in a particular embodiment, an siRNA is conjugated to a lipophilic moiety, wherein the lipophilic moiety is selected from the group consisting of cholesterol, vitamin D, DHA, DCA, etc. (see paragraph 0318).
Regarding claim 2, Khvorova teaches where the disclosure provides a branched oligonucleotide compound capable of mediating RNA silencing in a cell (a target), comprising two or more double-stranded nucleic acids. These branch oligonucleotides comprise of a 5’ and 3’ end (see paragraph 0093). Furthermore, an RNA silencing agent of the discloser can be administered ocularly, such as to treat a retinal disorder (see paragraph 0431).
Regarding claim 3, Khvorova teaches where the Di-siRNA branched oligonucleotides may comprise chemically diverse conjugates, wherein conjugated bioactive ligands may be used to enhance cellular specificity. Examples of bioactive moieties to be used for conjugation include DHAg2, DHA, GaINAc, and cholesterol (see paragraph 0356).
Regarding claim 4, Khvorova teaches where in certain embodiments, the RNA silencing agents provided herein are conjugated to one or more hydrophobic moieties (see paragraph 0329). It is disclosed that the hydrophobic moieties can include DHA (see paragraph 0339).
Regarding claim 5, Khvorova teaches the oligonucleotide comprises an antisense oligonucleotide (ASO) (see paragraph 0008) and Fig. 1A-1D schematically depicts four fully chemically stabilized siRNA patterns (see paragraph 0114).
Regarding claim 27, Khvorova teaches where the oligonucleotide comprising at least 14 contiguous nucleotides a the 5’ end and 3’ end, and greater than 50% 2’-O-methyl modifications to less than 85% 2’-O-methyl modifications (see paragraph 0007).
Regarding claim 34, Khvorova teaches where nucleotides from the 5’ end of the oligonucleotide comprises a non-2’-O-methyl modification or moiety (see paragraph 0011) and, in certain embodiments, the nucleotide at the 3’ end of the oligonucleotide comprises a non-2’-O-methyl modification or moiety (see paragraph 0012).
Regarding claim 43, Khvorova teaches an siRNA of the disclosure comprises a sense strand and/or an antisense strand (see paragraph 0168). In Fig. 4-6A, Khvorova teaches siRNA chemical patterns where from the 5’ end and 3’, the ribonucleotides from each end are connect to adjacent ribonucleotides with a phosphorothioate linkage (see figures).
Regarding claim 54 and 55, applicant recites wherein the oligonucleotide conjugate is administer by intravitreal injection. Intravitreal injection is known in the art as an injection directly to the eye. Khvorova teaches where the RNA silencing agent of the disclosure can be administered ocularly. Khvorova further specifies where the pharmaceutical composition can also be administered to the interior of the eye, and can be introduced by a needle or other delivery device which can introduce it to a selected area or structure (see paragraph 0431).
Regarding claim 73, Khvorova teaches wherein some embodiments, the hydrophobic moiety is docosanoic acid (DCA).
Regarding claim 75, Khvorova discloses Fig. 7C which depicts sFLT1i13 mRNA silencing in the placenta compared to a control (PBS). CD1 pregnant mice were treated with Pattern 3B or control siRNAs as recited in Fig. 7B. In Fig. 7C, 20/15-mer, 5’ VP siRNA shows sFLT1i13 mRNA expression as 50% of that relative to the PBS control, marking a 50% reduction in target nucleic acid expression, in vivo.
Regarding claim 76, Khvorova teaches where a ligand can be coupled with a conjugated carrier via an intervening tether. A ligand provides an enhanced affinity for a selected target, e.g., molecule, cell or cell type, a cellular organ compartment, tissue, organ, or region of the body (see paragraph 0320). It is disclosed in paragraph 0431 where the RNA silencing agent of the discloser can be administered to the eye.
Regarding claim 77, Khvorova teaches where an RNA silencing agent of the disclosure can be administered ocularly, such as to treat retinal disorder, e.g., a retinopathy (see paragraph 0431).
Regarding claim 94, Khvorova teaches where two or more RNA silencing agents, as disclosed above, may be connected to one another by one or more moieties independently selected from a linker, a spacer, and a branching point, forming a branched oligonucleotide containing two or more RNA silencing agents (see paragraph 0352).
Regarding claim 95, Khvorova teaches where in some embodiments, there is a third type of branched oligonucleotides including nucleic acids of both types, that is a nucleic acid comprising an antisense strand (or portions thereof) and an oligonucleotide comprising a sense strand (or portions thereof) (see paragraph 0352).
Regarding claim 96, Khvorova teaches where two or more RNA silencing agents, for example oligonucleotide constructs such as siRNAs, may be connected to one another by one or more moieties independently selected from a linker, a spacer, and a branching point (see paragraph 0352).
Regarding claim 97, Khvorova teaches where each linker is independently selected from an ethylene glycol chain, an alkyl chain, a peptide, RNA, DNA, a phosphate, a phosphonate, a phosphoramidate, an ester, an amide, a triazole, and combinations thereof.
Regarding claim 98, Khvorova teaches where in a particular embodiment, branched oligonucleotides of the present application have two to three oligonucleotides (see paragraph 0353).
Regarding claim 99, Khvorova teaches where an embodiment of the compound of formula (I), L has the structure of L2, which is a dimer as shown below (see paragraph 0387).
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In view of the foregoing, claims 1, 2, 3, 4, 5, 34, 43, 54, 55, 73, 75, 94, 95, 96, 97, 98, and 99 are rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 27, 34, 43, 54, 55, 73, 75, 76, and 77 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 65, 66, and 67 of copending Application No. 18/375,235. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 1, 5, 27, 34, 43, 54, 55, 73, 75, 76, and 77 of the instant application recites a method for delivering an oligonucleotide conjugate to an eye of the subject, the method comprising administering the oligonucleotide conjugate to the subject, wherein the oligonucleotide conjugate comprises a 5’ and 3’ end and complementary to a target nucleic acid, which is defined in claim 5 of the instant application as an antisense oligonucleotide or an siRNA, and a functional moiety, wherein the functional moiety comprises of docosanoic acid (DCA). Furthermore, the method of administering an oligonucleotide reduces expression of target nucleic acid and has affinity for a retinal protein. Though not recited in the claims, applicant defines in the specification that the targeted nucleic acid is S6K1 (or the protein encoded by S6K1) (See Fig. 22, 25, 27).
Claim 65 of the copending application recites a method for inhibiting expression of a S6K1 gene in a cell, the method comprising of introducing into the cell, the siRNA of claim 1 and maintaining the cell produced in step (a) for a time sufficient to obtain degradation of a mRNA transcript of the S6K1 gene, thereby inhibiting expression of the S6K1 gene in the cell.
The independent claim 1 and subsequent dependent claims of the copending application (which claim 65 of the copending application is dependent on) recites mechanistically identical steps to the instant application, with regard to siRNA composition. Since the specification of the instant application defines S6K1 is a primary knockdown target of the disclosed method (see paragraph 0272 of the instant specification), the claims listed in the instant application and the copending application have patentably indistinct structure, mechanism, and target.
Claim 66 of the copending application recites a method of treating or managing an eye disorder comprising administering to a patient in need of such treatment a therapeutically effective amount of siRNA of claim 1. Claim 67 of the copending application recites where the method of claim 66, wherein the siRNA is administered to an eye of the patient by intravitreal injection and/or the siRNA inhibits the expression of a S6K1 gene by at least 20% or at least 50%.
In the instant application, claims 54 and 55 discloses wherein the oligonucleotide conjugate is administered by intravitreal injection, and is delivered to an eye cell after administration to the subject. Claim 75 of the instant application discloses wherein the expression of the target nucleic acid is reduced by at least 20% and claim 76 recites wherein the oligonucleotide conjugate has selective affinity for a retinal protein. Claim 77 recites wherein the subject comprises an eye disorder.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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