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 .
Applicants’ reply to the April 10, 2026 Office Action, filed July 27, 2026, is acknowledged. Applicants amend claim 11. Claims 1-17 are pending in this application, and are under examination.
Any objection or rejection of record in the previous Office Action, mailed April 10, 2026, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments. This action is FINAL.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 1-17 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This rejection is maintained.
The claims recite a method of excising all or part of a viral sequence from a cell comprising cutting the viral sequence at a first and second target sequence, which results in all or part of the viral sequence being excised from the cell. The rejected claim thus comprises a genus of enzymes defined as belonging to a group proteins, to function to cleave a target nucleic acid. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. There are numerous types of CRISPR enzymes that will provide for cleavage of a viral sequence in a cell.
However, the specification states that “that we could eliminate the integrated HIV-1 genome from HIV-1 infected cells by using the RNA-guided Clustered Regularly Interspace Short Palindromic Repeat (CRISPR)-Cas9 nuclease system (Cas9/gRNA).” See paragraph [0028]. However, it is impossible for one to extrapolate from the generic recitation of broad classes of nuclease proteins, much less the broad classes of CRISPR proteins, the structure of any enzyme, or any CRISPR enzyme whose application to a nucleic acid molecule would be useful for detection of target nucleic acids. The prior art does not appear to offset the deficiencies of the instant specification. The prior art teaches that CRISPR Type I, II, and III enzymes each have different structures and function in different pathways (Sorek et al., 82 Annual Review of Biochemistry 237-266 (2013), and cited in the Information Disclosure Statement filed May 2, 2024). The prior art further discloses additional CRISPR systems, which also have different structures and function in yet different pathways (Koonin et al., 37 Current Opinion in Microbiology 67-78 (2017), and cited in the Information Disclosure Statement filed May 2, 2024). Thus, the specification is not sufficient to support the broadly claimed genus of CRISPR enzymes, which are variants having different structures and functions.
The description of the limited Cas9 CRISPR system is not sufficient to support the genus of claimed CRISPR systems. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, clearly states "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See Vas-Cath at page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is now is claimed." (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of CRISPR systems, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation or identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18USPQ2d 1016. Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-12.
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 §§ 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/patent/patents-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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 7-13 of U.S. Patent No. 9,925,248. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘248 patent and the instant application claim a method of inactivating a proviral DNA integrated in a host genome. It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that excising the proviral DNA according to the ‘248 patent using the instantly claimed method and composition would both result in the excision of the viral sequences, thus inactivating the virus.
Claims 1, 6, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9,981,020. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘020 patent claims a composition for excising a viral sequence from a cell and the instant application claims are directed to methods and compositions for excising a viral sequence from a cell. It would be obvious to one of ordinary skill in the art at the time the invention was made that the composition of U.S. Patent No. 9,981,020 in the method of the instant application because the composition will result in the recited excision of the viral sequence from the cell. The instant case is analogous to Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010), where the courts ruled that obviousness-type double patenting exist between previously-disclosed, but newly-claimed utility. Therefore, the instant claims are not patentably distinct from the issued claims.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,273,209. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘209 patent and the instant application claim methods of excising viral sequence from a cell. While the instant application does not claim use of a CRISPR/Cas9 endonuclease, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the ‘209 CRISPR method would function to be able to excise a viral sequence as required by the instant claims. In addition, the methods of the ‘209 patent provide for use of the instantly claimed method and composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 5-8 of U.S. Patent No. 11,285,193. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘193 patent and the instant application claim methods of excising viral sequence from a cell. While the instant application does not claim use of a CRISPR/Cas9 endonuclease, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the ‘193 CRISPR composition would be able to excise a viral sequence as required. In addition, the methods of the ‘193 patent provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,291,710. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘710 patent claims a composition which can be used for deletion of an HIV sequence from a cell and the instant application claims a method and composition for excising a viral sequence from a cell. Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the CRISPR compositions of the ‘710 patent could be used in the instant compositions, which would be able to delete/excise the retroviral sequence from the genome of the cell. The instant case is analogous to Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010), where the courts ruled that obviousness-type double patenting exist between previously-disclosed, but newly-claimed utility. Therefore, the instant claims are not patentably distinct from the issued claims. In addition, the methods of the ‘710 patent provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 5-6 of U.S. Patent No. 11,298,410. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘410 patent and the instant application claim method and compositions of excising viral sequence from a cell. While the instant application does not claim use of a CRISPR/Cas9 endonuclease, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the ‘410 CRISPR composition would be able to excise a viral sequence as required. In addition, the methods of the ‘410 patent provide for use of the instantly claimed method and composition. The instant case is analogous to Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010), where the courts ruled that obviousness-type double patenting exist between previously-disclosed, but newly-claimed utility. Therefore, the instant claims are not patentably distinct from the issued claims. Therefore, the claims are not deemed to be patentably distinct.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-7, and 28-31 of U.S. Patent No. 11,298,411. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘411 patent and the instant application claim method and compositions of excising viral sequence from a cell. While the instant application does not claim use of a CRISPR/Cas9 endonuclease, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the ‘411 CRISPR composition would be able to excise a viral sequence as required. In addition, the methods of the ‘411 patent provide for use of the instantly claimed method and composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,122,997. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘997 patent claims a vector composition and method for deletion of an HIV sequence from a cell and the instant application claims a method and composition for excising a viral sequence from a cell. Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the CRISPR vectors of the ‘997 patent could be used as the instant compositions and methods for deletion/excision of the retroviral sequence from the genome of the cell. The instant case is analogous to Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010), where the courts ruled that obviousness-type double patenting exist between previously-disclosed, but newly-claimed utility. Therefore, the instant claims are not patentably distinct from the issued claims. In addition, the methods of the ‘997 patent provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1, 6, and 11 are ejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,251,429. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘429 patent and the instant application claim a method for excising part or all of a viral sequence from the cell, where the instant application required deletion of an HIV sequence, where each method claims that the target sequences are in the LTR regions of the viral sequence. Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the methods of the ‘429 patent and the instant application would result in the deletion/excision of the retroviral sequence from the genome of the cell. In addition, the methods of the ‘429 patent provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1, 6, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-10 of U.S. Patent No. 12,644,121. This rejection is no longer provisional due to the issuance of the ‘121 patent on June 2, 2026.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘121 patent and the instant application each claim methods of eradicating a viral sequence from a cell. While the ‘121 patent does not explicitly claim excision of the viral sequence, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that excision of the viral sequence would eradicate the virus from a cell. In addition, the methods of the ‘121 patent provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
Claims 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10-14 of copending Application No. 16/812,140 (reference application). This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ’140 application and the instant application each claim methods of eradicating a viral sequence from a cell. While the ‘140 application does not explicitly claim excision of the viral sequence, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that excision of the viral sequence would eradicate the virus from a cell. In addition, the methods of the ‘140 application also provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 11-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 6-7 of copending Application No. 18/566,468 (reference application). This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘468 application and the instant application each claim compositions of eradicating a viral sequence from a cell. While the ‘468 application does not explicitly claim excision of the viral sequence, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that excision of the viral sequence would eradicate the virus from a cell. In addition, the compositions of the ‘468 application also provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 19/382,825 (reference application). This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ’825 application and the instant application each claim methods of eradicating a viral sequence from a cell. While the ‘825 application does not explicitly claim excision of the viral sequence, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that excision of the viral sequence would eradicate the virus from a cell. In addition, the methods of the ‘825 application provide for use of the instantly claimed composition. Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Amendments and Arguments
With regard to the rejection under 35 U.S.C. § 112(b)/second paragraph Applicants assertion that removal of part of a retroviral sequence sufficient to disrupt viral function is persuasive. With regard to the rejections 35 U.S.C. §§ 102(a)(2), and 103, Applicants’ arguments, in combination with a Declaration by T. J. Cradick filed in U.S. Patent No. 11,291,710, have been fully considered and are deemed to be persuasive (see the Declaration provided in the accompanying PTO-892). Therefore, the rejections under 35 U.S.C. §§ 112(b)/second paragraph, 102(a)(2), and 103 are withdrawn.
With regard to the rejection under 35 U.S.C. §§ 112(a)/first paragraph, Applicants’ arguments have been fully considered, but are not deemed to be persuasive.
Applicants assert that the specification provides disclosure of CRISPR-associated endonuclease compositions and their use in targeting retroviral sequences, specifically type I, II, and III systems and Cas9 molecules from a variety of species. Applicants further assert that, at the time of the filing date additional CRISPR-associated nucleases were known, and name Cas12a (Cpf1).
However, the rejection is based on the known effective CRISPR systems at the time of the provisional patent applications, at which time only the Type I, II, and III systems were known. And only Cas9, albeit from a variety of sources, was known to be useful in removal of all or part of retroviral sequences from eukaryotic cell. Cpf1 was not discovered to be useful in eukaryotic systems until 2015, and the earliest filing date of the instant application is August 29, 2013. In addition, the instant specification does not provide any disclosure other than a single sentence noting Types I-III (paragraph [0035]). And only Cas9 (Type II) was disclosed in any detail or exemplified. Thus, the specification does not provide adequate written description of any CRISPR system other than the exemplified Type II Cas9 CRISPR system. Therefore, this rejection is maintained.
Regarding the non-statutory double patenting rejections over U.S. Patent Nos. 9,925,248; 9,981,020; 11,273,209; 11,285,193; 11,291,710; 11,298,410; 11,298,411; 12,122,997; and 12,251,429; and U.S. Patent Application Nos. 16/605,922; 16/812,140; 18/566,468; and 19/382,825; Applicants requests that these rejections be held in abeyance until the claims are otherwise deemed allowable on their merits, and note that Applicants are willing to file terminal disclaimers as necessary to overcome the outstanding double patenting rejections. It is noted that the ‘922 application has been issued as U.S. Patent No. 12,644,121. Therefore, the rejection is no longer provisional.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mcintyre et al. (6 Retrovirology 55 1-15 (2009)), and cited in the Information Disclosure Statement filed May 2, 2024) discloses that RNA interference (RNAi) is a mechanism of gene suppression that may be useful in gene therapy applications for treating viral diseases, such as HIV-1 (abstract). Mcintyre 2014discloses the preparation of a variety of shRNAs based on the HIV-1 sequences, including those sequences found in the LTRs of HIV-1, which is interpreted as including the U3 region of the LTR (page 2 column 2, second paragraph, page 3, paragraph bridging columns 1 and 2, and page 4, column 2, second full paragraph).
THIS ACTION IS MADE FINAL. 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 NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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