Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the
DETAILED ACTION
Status of Application/Amendment/Claims
Applicant's response filed 08/07/2025 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 03/07/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 08/07/2025, claims are pending. Claims 1-35 and 39 are currently under examination. Claims 36-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The replacement Drawings are accepted and the rejection is withdrawn.
The amendments to the Specification are accepted and is in sequence compliance.
The 112(b) rejection is withdrawn in response to Applicant’s arguments.
The 102 rejection is withdrawn in view of the new rejections herein.
New Claim Rejections
Claim Interpretation:
The specification describes structures conceptualized by the claimed structure in at least Figure 1. The limitations above describe the structure as forming a double stranded molecule wherein X contains nucleotides complementary to nucleic acid sequences of Y, thus forming a double stranded oligonucleotide connected by linker L.
The specification describes the structure in [0012] The inventors of the present invention found that, by coupling an oligodeoxyribonucleotide and a complementary chain containing its corresponding -3-RNA with a linker such as DNA or RNA that is degraded under physiological conditions to obtain a single-stranded oligonucleotide having a structure that partially hybridizes within a molecule thereof and has an antisense sequence capable of controlling expression of a target gene, the single-stranded oligonucleotide 5demonstrates an antisense effect that is equal to or greater than that of the double-stranded oligonucleotide.
Thus for prior art purposes, the claimed oligonucleotide forms a double stranded structure as described.
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 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)(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 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 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.
Claim(s) 1-35 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McSwiggen et al. (US 20070032441 cited on IDS 11/11/22).
Regarding claims 1-4 and 6, McSwiggen et al. teach a single stranded molecule wherein one strand is an antisense strand and the other is a sense strand that are connected to a linker molecule that can be a polynucleotide linker or a non-nucleotide linker (0032). McSwiggen et al. teach a linear hairpin structure or an asymmetric hairpin structure that can be 36-70 with having about 3 to 25 base pairs and (0043-0044) wherein loop is biodegradable (0112-0113). McSwiggen et al. teach the X and Y can bind the L on the 5’ or 3’ side (Figure 97). This structure would anticipate the claimed structure of X-L-Y with X and Y being antisense and sense strands and L being a linker.
Regarding claim 5, McSwiggen teach examples of linkers that can be phosphodiester linkages (0540-0550).
Regarding claims 7-14, 16, 17, 26-29, McSwiggen et al. teach oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2'-amino, 2'-C-allyl, 2'-fluoro, 2'-O-methyl, 2'-O-allyl, 2'-H, nucleotide base modifications, deoxyribonucleotides or phosphorothioate linkages and teach the modified nucleotides can be from 5-100% in each strand (see at least 0020-0021,0008, 0019).
Regarding the limitation of “contains at least four contiguous nucleotides recognized by RNase H”, the specification describes that RNase H can recognize a double strand in which at least one of the base moiety, phosphodiester bond moiety or sugar moiety of at least one of DNA and RNA has been modified [0025]. McSwiggen et al. teach base, sugar or phosphodiester modification can be from 5-100% of each strand and thus it would encompass having at least four contiguous nucleotides recognized by RNase H.
Regarding claims 15 and 20, teach replacing only 2 nucleotides in the end regions of each strand with deoxyribonucleotides (0019-022) but does not teach an oligonucleotide containing four contiguous deoxyribonucleotides.
Regarding claims 18 and 21-25, McSwiggen et al. teach embodiments of a multifunctional siRNA wherein the 5’ end of an antisense strand (X) linked to the 3’ end of another antisense strand (X’), wherein the linkers can be nucleotide based or biodegradable linkers as described in the description above or known in the art (see at least 0474-476) and the linkers can be phosphorothioate (0658-0661). McSwiggen et al. teach advantages to the multifunctional siRNA such as targeting two different genes (see 0477).
Regarding claims 30-35 and 39, McSwiggen et al. teach the oligonucleotide can be in pharmaceutical compositions and teach conjugates and/or complexes that can be used “to facilitate delivery of siNA molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. The present invention encompasses the design and synthesis of novel conjugates and complexes for the delivery of molecules, including, but not limited to, small molecules, lipids, cholesterol, phospholipids, nucleosides, nucleotides, nucleic acids, antibodies, toxins, negatively charged polymers and other polymers, for example, proteins, peptides, hormones, carbohydrates, polyethylene glycols, or polyamines, across cellular membranes. In general, the transporters described are designed to be used either individually or as part of a multi-component system, with or without degradable linkers…Conjugates of the molecules described herein can be attached to biologically active molecules via linkers that are biodegradable, such as biodegradable nucleic acid linker molecules” (see para.0496). McSwiggen et al. teach using the siRNA to target specific cell types such as targeting the asialoglycoprotein receptor (see 0770) and teach a sugar conjugate N-acetyl-galactosamine (0552). McSwiggen et al. teach methods of design and synthesis of said molecules (see 0808-0813).
Thus McSwiggen et al. anticipates the instant claims.
Claim(s) 1-3, 6, 12, 13, 17 and 24-29 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Inturrisi et al. (US 20110293628).
Regarding claims 1-3 and 6, Inturrisi et al. teach a single stranded molecule wherein one strand is an antisense strand and the other is a sense strand that are connected to a linker molecule that can be a polynucleotide linker or a non-nucleotide linker wherein the X and Y can bind the L on the 5’ or 3’ side (0010, 0091). This structure would anticipate the claimed structure of X-L-Y with X and Y being antisense and sense strands and L being a linker.
Regarding claims 12, 13, 17 and 24-29, Inturrisi et al. teach oligonucleotides can comprise modified backbones, internucleotide linkages and sugar modifications (see at least 0093-0096).
Thus Inturrisi et al. anticipates the instant claims.
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 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 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.
Claims 1-35 and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over McSwiggen et al. (US 20070032441) and Yakota et al. (US 20140302603).
The claims are drawn to a single-stranded oligonucleotide represented by the formula X-L-Y wherein the first oligonucleotide has a nucleotide sequence X, and the second oligonucleotide has a nucleotide sequence Y, the nucleotide sequence X contains a first nucleotide sequence that is capable of hybridizing with at least a portion of the second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H, the nucleotide sequence Y contains a second nucleotide sequence that is capable of hybridizing with at least a portion of the first oligonucleotide and contains at least one ribonucleotide, at least one of the nucleotide sequence X and the nucleotide sequence Y contains at least one antisense sequence capable of hybridizing with a target RNA.
Regarding claims 1-4 and 6, McSwiggen et al. teach a single stranded molecule wherein one strand is an antisense strand and the other is a sense strand that are connected to a linker molecule that can be a polynucleotide linker or a non-nucleotide linker (0032). McSwiggen et al. teach a linear hairpin structure or an asymmetric hairpin structure that can be 36-70 with having about 3 to 25 base pairs and wherein loop is biodegradable (0112-0113). McSwiggen et al. teach the X and Y can bind the L on the 5’ or 3’ side (Figure 97). This structure would anticipate the claimed structure of X-L-Y with X and Y being antisense and sense strands and L being a linker.
Regarding claim 5, McSwiggen teach examples of linkers that can be phosphodiester linkages (0540-0550).
Regarding claims 7-14, 16, 17, 26-29, McSwiggen et al. teach oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2'-amino, 2'-C-allyl, 2'-fluoro, 2'-O-methyl, 2'-O-allyl, 2'-H, nucleotide base modifications, deoxyribonucleotides or phosphorothioate linkages and teach the modified nucleotides can be from 5-100% in each strand (see at least 0020-0021,0008, 0019).
Regarding the limitation of “contains at least four contiguous nucleotides recognized by RNase H”, the specification describes RNase H can recognize a double strand in which at least one of the base moiety, phosphodiester bond moiety or sugar moiety of at least one of DNA and RNA has been modified [0025]. McSwiggen et al. teach base, sugar or phosphodiester modification can be from 5-100% of each strand and thus it would encompass having at least four contiguous nucleotides recognized by RNase H.
Yakota et al. teach a nucleotide strand having at least four or more contiguous nucleotide recognized by RNase H is advantageous to promote cleavage (0129). Thus it would have been obvious to one of ordinary skill in the art to incorporate at least 4 contiguous nucleotides into the strands taught by McSwiggen et al. that are recognized by RNase H to promote cleavage.
Regarding claims 15 and 20, McSwiggen et al. teach replacing only 2 nucleotides in the end regions of each strand with deoxyribonucleotides (0019-022) but does not teach or suggest an oligonucleotide containing four contiguous deoxyribonucleotides.
Regarding claims 18, 19 and 21-25, McSwiggen et al. teach embodiments of a multifunctional siRNA wherein the 5’ end of an antisense strand (X) linked to the 3’ end of another antisense strand (X’), wherein the linkers can be nucleotide based or biodegradable linkers as described in the description above or known in the art (see at least 0474-476) and the linkers can be phosphorothioate (0658-0661). McSwiggen et al. teach advantages to the multifunctional siRNA such as targeting two different genes (see 0477).
Regarding claims 30-35 and 39, McSwiggen et al. teach the oligonucleotide can be in pharmaceutical compositions and teach conjugates and/or complexes that can be used “to facilitate delivery of siNA molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. The present invention encompasses the design and synthesis of novel conjugates and complexes for the delivery of molecules, including, but not limited to, small molecules, lipids, cholesterol, phospholipids, nucleosides, nucleotides, nucleic acids, antibodies, toxins, negatively charged polymers and other polymers, for example, proteins, peptides, hormones, carbohydrates, polyethylene glycols, or polyamines, across cellular membranes…Conjugates of the molecules described herein can be attached to biologically active molecules via linkers that are biodegradable, such as biodegradable nucleic acid linker molecules” (see para.0496). McSwiggen et al. teach using the siRNA to target specific cell types such as targeting the asialoglycoprotein receptor (see 0770) and teach a sugar conjugate N-acetyl-galactosamine (0552). McSwiggen et al. further teach methods of design and synthesis of said molecules (see 0808-0813).
Therefore it would have obvious to use the oligonucleotide structure of McSwiggen et al. and incorporate four contiguous nucleotides recognized by RNase H, wherein the nucleotides are not all deoxyribonucleotides, comprises modified nucleotides and can be a multimeric composition as taught above to target the same or different genes for inhibition of gene expression.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim Rejections - 35 USC § 112
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.
Claim 1-35 and 39 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 pre-AIA the applicant regards as the invention.
Claim 1 recites "in the case of having two or more antisense sequences, the target RNA hybridized by each antisense sequence may be the same or different, wherein X and Y hybridize by the first nucleotide sequence portion and the second nucleotide sequence portion.” This limitation is indefinite because the claim recites Y is 4-100 nucleotides in length and it is unclear how this sequence can have one or more antisense sequence encompassed in a sequence of only 4 nucleotides. Claims 2-35 and 39 are rejected as they depend or encompass claim 1.
Maintained Rejections
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. See 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);and, 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-35 and 39 are provisionally rejected under the judicially created doctrine of double patenting over claims 1-43 and 45 of Patent No 11,530,409. This is a provisional double patenting rejection since the conflicting claims have not yet been patented. Although the conflicting claims are not identical, they are not patentably distinct from each other.
Patent ‘409 and the instant claims are drawn to a single-stranded oligonucleotide represented by the formula X-L-Y wherein the first oligonucleotide has a nucleotide sequence X, and the second oligonucleotide has a nucleotide sequence Y, the nucleotide sequence X contains a first nucleotide sequence that is capable of hybridizing with at least a portion of the second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H, the nucleotide sequence Y contains a second nucleotide sequence that is capable of hybridizing with at least a portion of the first oligonucleotide and contains at least one ribonucleotide, at least one of the nucleotide sequence X and the nucleotide sequence Y contains at least one antisense sequence capable of hybridizing with a target RNA.
Response to Applicant’s Arguments
Applicant argues the instant claims and claims of Patent ‘409 do not define the formula X-L-Y in the same manner because Patent ‘409 recites that "the nucleotide sequence X contains at least one antisense sequence capable of hybridizing with a target RNA," whereas the claims [of] the present application do not recite that the nucleotide sequence X contains at least one antisense sequence capable of hybridizing with a target RNA. Applicant further argues “the claims of the present application recite that "the nucleotide sequence Y contains at least one antisense sequence capable of hybridizing with a target RNA," whereas the claims of the '409 patent do not recite that the nucleotide sequence Y contains at least one antisense sequence capable of hybridizing with a target RNA.”
This argument is factually incorrect. Claim 1 of Patent ‘409 recites that in the formula X-L-Y, X or Y can contain an antisense sequence as shown highlighted in a reprint of the claim as printed in the patent and as previously stated in the rejection:
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Thus the scope of the instant claims and the claims of Patent ‘409 overlap in scope are not are not patentably distinct from each other.
Conclusion
No claims are allowed.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636