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 .
Claims 1, 7, 34, 35, 38, 40, 41, 43-47, 51, 54, 58, 61, 62, 68, 91, 93, 96, 119, 123, 124, 126, 127 are pending.
Claims 2-6, 8-33, 36, 37, 39, 42, 48-50, 52, 53, 55-57, 59, 60, 63-67, 69-90, 92, 94, 95, 97-118, 120-122, and 125 are cancelled.
Claims 38, 40, 41, 43-47, 51, 54, 61, 62, 68, 119, 123, and 124 are withdrawn.
Claims 1, 7, 58, 91, and 126-127 are amended.
Claims 1, 7, 34, 35, 58, 91, 93, 96, 126 and 127 are currently being examined.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/11/2025 has been entered.
Claim Objections
Claim 35 objected to because of the following informalities: the formula "R3-(0-CH2-CH2)n-O-" has the number 0 instead of the letter O. Appropriate correction is required.
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.
In regard to claim 7, the “cholesterol or derivative thereof” does not meet the written description provision of 35 USC § 112, first paragraph, due to lacking chemical structural information for what they are and chemical structures are highly variant and encompass a myriad of possibilities. The specification provides insufficient written description to support the genus of derivatives of cholesterol encompassed by the claim, since there is no description of the structural relationship of these derivatives provided in the specification and Applicant has not provided a description as to how the base molecule may be changed while remaining a derivative.
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, 7, 34, 35, 58, 91, 93, 96 and 126-127 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 77, and 85 of copending Application No. 18/546,131 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application recites an extracellular vesicle comprising a biologically active molecule covalently linked to the EV via an anchoring moiety (claim 1). The anchoring moiety comprises a linker and spacers (claim 1), including a cholesterol (claim 77), TEG (claim 77), phosphorothioate (claim 85) and phosphodiesterase/phosphodiester (claim 85).
The difference between instant application and the patented claims is that the patent claims include additional limitations. Thus, the invention of the patent is in effect a “species” of the “generic” invention of the application claims. It has been held that the generic invention is “anticipated” by the “species”, and, therefore, the application claims are not patentably distinct from the claims of the patent and are rejected on the ground of nonstatutory obviousness-type double patenting. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 7, 34, 35, 58, 91, 93, 96 and 126-127 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 144 of copending Application No. 18/050,017 (reference application) in view of HARASZTI (Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles. Molecular Therapy. 2018.).
The copending application recites an extracellular vesicle comprising an antisense oligonucleotide (ASO), which reads on biologically active molecule (claim 144). The vesicle further comprises a cholesterol (claim 144) an anchoring moiety (claim 144). The anchoring moiety comprises a linker (claim 144), a phosphorothioate (claim 144).
The application does not teach using triethylene glycol (TEG) and phosphodiester.
HARASZTI teaches extracellular vesicles that are conjugated to siRNA, which reads on a biologically active molecule, via a linkage (abstract), which reads on anchoring moiety. The linkage comprises a cholesterol (abstract), which reads on sterol, conjugated to triethylene glycol (TEG) (figure 1), that is further conjugated to a phosphorodiester/phosphodiester (PO) and phosphorothioate (PS) that is then connected to the siRNA (figure 4). TEG provided productive exosomal loading (abstract). The phosphodiester linkage, and the overall linkages in general, can be modified to modulate the rate of cholesterol cleavage (page 1977, paragraph 2)
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate TEG and phosphodiester. The person of ordinary skill in the art would have been motivated to make those modifications, because TEG provides productive exosomal loading and phosphodiester linkage, in general all forms of linkage combination, can be modified to modulate the rate of cholesterol cleavage, and reasonably would have expected success because the references are in the same field of endeavor, such as extracellular vesicles delivering biologically active molecules that utilize cholesterol and various linkers/spacers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 7, 34, 35, 58, 91, 93, 96 and 126-127 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 41, 50, and 52 of copending Application No. 18/546,130 (reference application) in view of HARASZTI (Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles. Molecular Therapy. 2018.).
The copending application recites an extracellular vesicles comprising an siRNA (claims 1 and 3). The vesicle comprises an anchoring moiety (claim 50) and a phosphorothioate (claim 41), and a linker (claim 52).
The application does not teach using triethylene glycol (TEG), phosphodiester and cholesterol.
HARASZTI teaches extracellular vesicles that are conjugated to siRNA, which reads on a biologically active molecule, via a linkage (abstract), which reads on anchoring moiety. The linkage comprises a cholesterol (abstract), which reads on sterol, conjugated to triethylene glycol (TEG) (figure 1), that is further conjugated to a phosphorodiester/phosphodiester (PO) and phosphorothioate (PS) that is then connected to the siRNA (figure 4). TEG provided productive exosomal loading (abstract). The cholesterol enables efficient and reproductible loading of the vesicle with the siRNA (abstract). The phosphodiester linkage, and the overall linkages in general, can be modified to modulate the rate of cholesterol cleavage (page 1977, paragraph 2)
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate TEG, cholesterol and phosphodiester. The person of ordinary skill in the art would have been motivated to make those modifications, because TEG provides productive exosomal loading, the cholesterol enables efficient and reproductible loading of the vesicle with the siRNA and phosphodiester linkage, in general all forms of linkage combination, can be modified to modulate the rate of cholesterol cleavage, and reasonably would have expected success because the references are in the same field of endeavor, such as extracellular vesicles delivering siRNA that utilize various linkers/spacers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 7, 34, 35, 58, 91, 93, 96 and 126-127 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 36, 88, and 90 of copending Application No. 17/635,298 (reference application) in view of HARASZTI (Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles. Molecular Therapy. 2018.).
The copending application recites an extracellular vesicle comprising an antisense oligonucleotide (claim 1), which reads on biologically active molecule. The vesicle further comprises an anchoring moiety and linker (claim 36 and 88), which includes TEG and cholesterol (claim 90).
The application does not teach using phosphorothioate and phosphodiester.
HARASZTI teaches extracellular vesicles that are conjugated to siRNA, which reads on a biologically active molecule, via a linkage (abstract), which reads on anchoring moiety. The linkage comprises a cholesterol (abstract), which reads on sterol, conjugated to triethylene glycol (TEG) (figure 1), that is further conjugated to a phosphorodiester/phosphodiester (PO) and phosphorothioate (PS) that is then connected to the siRNA (figure 4). The phosphorothioate modification provided additional stabilization (page 1976, paragraph 1). The phosphodiester linkage, and the overall linkages in general, can be modified to modulate the rate of cholesterol cleavage (page 1977, paragraph 2)
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate phosphorothioate and phosphodiester. The person of ordinary skill in the art would have been motivated to make those modifications, because the phosphorothioate modification provided additional stabilization and phosphodiester linkage, in general all forms of linkage combination, can be modified to modulate the rate of cholesterol cleavage, and reasonably would have expected success because the references are in the same field of endeavor, such as extracellular vesicles delivering siRNA that utilize various linkers/spacers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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, 7, 34, 35, 58, 91, 93, and 96 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by HARASZTI (Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles. Molecular Therapy. 2018.).
Regarding claim 1, HARASZTI teaches extracellular vesicles that are conjugated to siRNA, which reads on a biologically active molecule, via a linkage (abstract), which reads on anchoring moiety. The linkage comprises a cholesterol (abstract), which reads on sterol, conjugated to triethylene glycol (TEG) (figure 1), that is further conjugated to a phosphorodiester/phosphodiester (PO) and phosphorothioate (PS) that is then connected to the siRNA (figure 4).
Regarding claim 7, HARASZTI teaches a cholesterol is used (abstract).
Regarding claim 34, HARASZTI teaches using TEG (figure 4), which is a polyethylene glycol.
Regarding claim 35, HARASZTI teaches using TEG (figure 4), which has the formula of H-(O-CH2-CH2)3-O.
Regarding claim 58, HARASZTI teaches that TEG, PO and PS are used (figure 4)
Regarding claim 91, HARASZTI teaches that the siRNA is conjugated onto the extracellular vesicle (abstract), which reads on covalently linked on an exterior surface.
Regarding claims 93 and 96, HARASZTI teaches that the biologically active molecule is an siRNA, which reads on a polynucleotide.
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, 7, 34, 35, 58, 91, 93, 96 and 126-127 are rejected under 35 U.S.C. 103 as being unpatentable over HARASZTI (Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles. Molecular Therapy. 2018.) in view of MANAHARAN (US 8,828,956 B2).
HARASZTI teaches Applicant’s invention as discussed above.
HARASZTI does not teach adding a C3 or C6 spacer.
Regarding claim 126 and 127, MANAHARAN teaches a method of delivering siRNA by conjugating it to cholesterol (column 3, paragraph 1 and 3). Various spacers can be used and combined such as C3, C6, and TEG (column 73, paragraph 2). These spacers help to stabilize the composition (column 73, paragraph 2). MANAHARAN further teaches using a phosphodiester and phosphorothioate linkage (column 54, paragraph 8).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a C3 or C6 spacer. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because C3 and C6 and TEG, which is used in HARASZTI, are functional equivalents of spacers commonly used in the pharmaceutical industry for delivering siRNA when it is conjugated to cholesterol. Furthermore these spacers helped to stabilize the composition.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 7, 34, 35, 58, 91, 93, 96, 126 and 127 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Furthermore, as discussed above HARASZTI teaches using a PS linker.
Conclusion
No claims are allowable.
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/S.L.M./Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618