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 .
Election/Restrictions
The restriction for claim 48 remains. The claim was cancelled in the amendment filed on 12/19/15.
Response to Arguments
Applicant’s arguments, see pages 4-8, filed 12/19/25, with respect to the rejections of claims 1, 5, 6, 8, 42, and 49-55 under 103 and NSDP rejections have been fully considered and are persuasive. Therefore, the rejections have been withdrawn because the prior art cited in the 103 or claims from issued U.S. Patents do not teach or suggest making a translation-incompetent circular polyribonucleotide comprising a guide RNA (gRNA) or complement thereto. However, upon further consideration, a new ground(s) of rejection is made in view of the amendment to independent claim 1 to limit the circular polyribonucleotide to a translation-incompetent circular polyribonucleotide not encoding an expression sequence. Note: removing the term ‘an expression sequence’ does limit the polyribonucleotide to a non-coding sequence (a guide RNA or complement thereto) even with the term ‘comprises a guide RNA or complement thereto’.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See page 58.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 5-6, 8, 42, and 49-55 are rejected under 35 U.S.C. 103 as being obvious over Flagship Pioneering (US 20210292761, EFD 7/24/18, cited on an IDS).
The applied reference has a common assignee and inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
‘761 teaches : A pharmaceutical composition comprising a translation incompetent circular polyribonucleotide comprising an aptamer sequence, wherein the aptamer sequence has a secondary structure that binds the target; and a pharmaceutically acceptable carrier or excipient (pages 35-57). In some embodiments, the circular polyribonucleotide comprises a DNA binding site, such as a sequence for a guide RNA (gRNA). In some embodiments, the circular polyribonucleotide comprises a guide RNA or a complement to a gRNA sequence (page 16). Pages 35-58 discloses making a circular RNA that binds a targeted nucleic acid molecule, e.g., DNA (dsDNA) or RNA. The binding of the circular RNA to the molecule can be used to regulate gene expression. Pages 42-58 disclose placing the circular RNA in a buffer (RNase free water). Example 23 on page 49 discloses a guide strand of a siRNA in a circular RNA, but the example does not appear to teach the circular RNA being in a composition comprising a buffer. Paragraph 170 discloses:
In some embodiments, circRNA described herein sequesters a target, e.g., DNA, RNA, proteins, and other cellular components to regulate cellular processes. CircRNA with binding sites for a target of interest can compete with binding of the target with an endogenous binding partner. In some embodiments, circRNA described herein sequesters miRNA. In some embodiments, circRNA described herein sequesters mRNA. In some embodiments, circRNA described herein sequesters proteins. In some embodiments, circRNA described herein sequesters ribosomes. In some embodiments, circRNA described herein sequesters other circRNA. In some embodiments, circRNA described herein sequesters non-coding RNA, lncRNA, miRNA, tRNA, rRNA, snoRNA, ncRNA, siRNA, or shRNA. In some embodiments, circRNA described herein includes a degradation element that degrades a sequestered target, e.g., DNA, RNA, protein, or other cellular component bound to the circRNA. Non-limiting examples of circRNA sequestration applications are listed in TABLE 2.
However, ‘761 does not specifically teach a parenteral delivery system comprising a translation incompetent circular polyribonucleotide and a parenterally acceptable diluent, wherein the polyribonucleotide comprises a gRNA or a complement thereto, wherein the system is free of any carrier.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to make a nucleic acid system comprising a translation incompetent circular polyribonucleotide comprising a gRNA and a parenteral acceptable carrier, namely to arrive at the claimed invention. With respect to the term ‘parenteral’ in the pre-amble and ‘parenterally acceptable diluent’ of the instant claim; Paragraph 43 of the as-filed specification defines “parenterally acceptable diluent” as a diluent for parenteral administration of a composition (e.g., a composition comprising a circular polyribonucleotide). In view of the broadest reasonable interpretation (BRI) of the term "parenteral nucleic acid delivery system", the pre-amble embraces any composition (e.g., water, solvents, RNA stabling agent, a buffer, an isotonic agent, or a mixture thereof). Furthermore, the limitation ‘system is free of any carrier’ is obvious over ‘761 (e.g., pages 33-34) because ‘761 discloses placing the circular polyribonucleotide in water. Also, the product could read on the system before being conjugated or placed in a carrier. In addition, it would have been obvious to make the product and deliver to a cell since circular polyribonucleotide are stable structures (paragraph 155). Example 23 on page 49 discloses a guide strand of a siRNA in a circular RNA. The limitation ‘wherein the parenteral nucleic acid delivery system is formulated for intravenous, subcutaneous, intramuscular, ophthalmic, or topical administration’ in claim 6 is directed to an intended use of the system and does not add any additional structural limitations that need to be made obvious by ‘761 (e.g., pages 33-34). The limitation in instant claim 8 is an intended use of the claimed product because it is a 'wherein' clause when the guide RNA or complement thereof forms a complex with a target nucleic acid either in a test tube, cell, or a subject. "Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure." See MPEP 2111.04. The limitation 'wherein the target molecule is selected from... in instant claims 49-55 are directed ‘wherein’ clauses embracing a functional limitation of intended use of the claimed product. The claims are directed to a product and not a method of using the product. There are no additional structures that need to be made obvious by the teaching in the cited prior art. Pages 35-58 of ‘761 disclose making a circular RNA that binds a targeted nucleic acid molecule, e.g., DNA (dsDNA) or RNA. The binding of the circular RNA to the molecule can be used to regulate gene expression.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claims 1, 5-6, 8, 42, and 49-55 are rejected under 35 U.S.C. 103 as being unpatentable over Pachuk et al. (WO0063364).
Pachuk teaches a composition for inhibiting the function of a target polynucleotide sequence in a cell comprising a pharmaceutical composition comprising at least partially double stranded RNA (dsRNA) and a carrier, wherein one strand of the RNA hybridizes to a target sequence (gene, cancer gene, viral) in a cell (pages 5-55). This RNA molecule does not produce a functional protein. Pachuk also discloses making circular RNA comprising a non-coding sequence, wherein the sequence comprises a sense sequence and an antisense sequence to a region of targeted sequence (pages 9 and 15). When the RNA is homologous to a target polynucleotide from a virus and the dsRNA is delivered to a cell infected with a virus, the RNA reduces and turns off the sequence and the sequence in other cells is degraded thru RNA degradation. Page 22 discloses a carrier can be saline, phosphate, buffered saline, dextrose, sterilized water, glycerol, ethanol, lactose, sucrose, and water and combinations thereof. Selection of an appropriate carrier in accordance with the mode of administration is routinely performed by those of skill in the art (page 23). Pages 24-25 disclose that the pharmaceutical composition can be for parenteral administration.
However, Pachuk does not specifically teach a parenteral delivery system comprising a translation incompetent circular polyribonucleotide and a parenterally acceptable diluent, wherein the polyribonucleotide comprises a gRNA or a complement thereto, wherein the system is free of any carrier.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to make a composition comprising the translation incompetent circular RNA in a pharmaceutical composition used for parenteral administration, namely to arrive at the claimed invention. See MPEP 2143(I)(E) “obvious to try”. The broadest reasonable interpretation of the term ‘gRNA or complement thereto’ recited in instant claim 1 embraces either strand of a siRNA, including a guide RNA, which is the antisense strand of the siRNA. With respect to the term ‘parenteral” recited in the instant claims, Pachuk teaches making a composition for parenterally administration. Furthermore, the limitation ‘system is free of any carrier’ is obvious over Pachuk because the product could read on the system before being conjugated or placed in a carrier (sterilized water). The limitation ‘wherein the parenteral nucleic acid delivery system is formulated for intravenous, subcutaneous, intramuscular, ophthalmic, or topical administration’ in claim 6 is directed to an intended use of the system and does not add any additional structural limitations that need to be made obvious by Pachuk. In addition, Pachuk teaches making the composition suitable for the administration routes set forth in claim (pages 24-25). The limitation in instant claim 8 is an intended use of the claimed product because it is a 'wherein' clause when the guide RNA or complement thereof forms a complex with a target nucleic acid either in a test tube, cell, or a subject. See MPEP 2111.04. The limitation 'wherein the target molecule is selected from... in claims 49-55 are directed ‘wherein’ clauses embracing a functional limitation and/or intended use of the claimed product. The claims are directed to a product not a method of using the product and there are no additional structures that need to be made obvious by Pachuk. Pachuk teaches using the composition to inhibit the function of polynucleotide sequences (pages 2-3, 7 and 28-32). When the RNA is homologous to a target polynucleotide from a virus and the dsRNA is delivered to a cell infected with a virus, the RNA reduces and turns off the sequence and the sequence in other cells is degraded thru RNA degradation.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
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, 5-6, 8, 42, and 49-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-48, 50-56, and 58-66 of copending Application No. 17262591(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims embrace a translation incompetent circular polyribonucleotide comprising a nucleotide sequence, wherein the sequence is a guide RNA or complement thereto. The only difference is the instant claims are directed to a product and the claims from ‘591 are directed to a method of using the product. The claims from ‘591 do not specifically recite a parenteral nucleic acid delivery comprising the polyribonucleotide comprising a guide RNA or a complement thereof. One of ordinary skill in the art would look to the disclosure of ‘591 for the structure of the polyribonucleotide and arrive at paragraphs 147-149. With respect to the term ‘parenteral” in the pre-amble of the instant claims, one of ordinary skill in the art would look at the disclosure of ‘591 for how the polyribonucleotide is delivered and would arrive at the paragraphs. These paragraphs would make obvious the term in the pre-amble. In addition, the broadest reasonable interpretation (BRI) of the term "parenteral nucleic acid delivery system" in preamble embraces any composition (e.g., water, solvents, RNA stabling agent, a buffer, an isotonic agent, or a mixture thereof). Furthermore, the claims of ‘591 make obvious the limitation ‘system is free of any carrier’ because it makes obvious the system with no additional carrier. The limitation in instant claim 8 is an intended use of the claimed product because it is a 'wherein' clause when the guide RNA or complement thereof forms a complex with a target nucleic acid either in a test tube, cell, or a subject. See MPEP 2111.04. The limitation 'wherein the target molecule is selected from... in instant claims 49-55 are directed to ‘wherein’ clauses embracing a functional limitation and/or an intended usage of the claimed product.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
See attached PTO-326 for disposition of claims.
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 Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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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/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636