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 .
Claim Status
Claims 1-103 are cancelled.
Claims 104-113 are presented for examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63086648, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The application fails to provide support for the claims under examination, since there is no disclosure regarding SEQ ID NO 364-377. Therefore, the effective filling date of claims 104-109 is deemed to be November 11, 2020, the filling date of the application PCT/US2020/059954.
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 104-105, 107-110 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Roehm et al. (“Roehm”, US 2018/0000970 A1).
Regarding claim 104, 107, Roehm teaches composition for treating or preventing a herpesvirus infection. The composition comprises a) a CRISPR-associated (Cas) peptide or an isolated nucleic acid encoding a Cas peptide; and b) an isolated guide nucleic acid or an isolated nucleic acid encoding a guide nucleic acid, where the guide nucleic acid comprises a nucleotide sequence substantially complementary to a target sequence in the herpesvirus genome (e.g., paragraph 0007). Roehm teaches SEQ ID NO 15 (ICP4) that has 100% homology with SEQ ID NO 370 (e.g., paragraph 0099; Table 3 (ICP4) [see below]).
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Regarding claim 105, Raehm teaches gRNA target sites containing a 20 bp guide sequences (e.g., Table 4).
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Regarding claim 108, Roehm teaches effective gRNA (2A) was 30 nt in length plus NGG. It showed no evidence for InDel mutation in any of a series of five representative off-target host genes identified by bioinformatic screening using shorter (12 nt) seed sequences corresponding to target
A of ICP0 exon II (e.g., paragraph 0252; Fig. 2).
Regarding claim 109, Roehm teaches composition includes a vector derived from an adeno-associated virus (AAV). Adeno-associated viral (AAV) vectors have become powerful gene delivery tools for the treatment of various disorders (e.g., paragraph 0149).
Regarding claim 110, Roehm teaches CRISPR/ Cas9 system can be refined and used for protecting cells against HSV-1 infection. The pre-existence of Cas9 plus gRNAs 2A in human cells that robustly support HSV-1 replication prevented efficient replication of the incoming HSV-1. CRISPR/Cas9 gene editing system and the complexity of HSV-1 lytic infection cycle, a combination therapy can be developed that includes
a cocktail of gRNAs for targeting important viral proteins involved in the regulation of the immediate early, early and late phases of HSV-1 infection (it reads on multiple guide RNAs) (e.g., paragraph 0253). Lentivirus-mediated delivery of Cas9 and gRNAs during viral infection significantly decreased viral loads produced by infected cells. Results from combinatory experiments presented herein using ICP0 gRNA plus either ICP4 gRNA or ICP27 gRNA showed complete elimination of HSV1 replication in the infected cells (it reads on multiple guide RNAs, and gRNAs targeting different regions on ICPO gene and one ICP27 gene). The use of a specific order first and second gRNAs targeting IPC0 gene and a third gRNA targeting ICP27 gene is merely a design choice (e.g., paragraph 0251; Tables 3-4).
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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.
Claim 106 is rejected under 35 U.S.C. 103 as being unpatentable over Roehm et al. (“Roehm”, US 2018/0000970 A1) as applied to claims 104-105, 107-110 above, and further in view of Bentwich et al. (“Bentwich”, US 7,795,419 B2).
Roehm does not teach a SEQ ID NO 372 or 373, as required by instant claims 111-113. However, this is cured by Bentwich.
Bentwich teaches nucleotide sequences of viral and viral-associated miRNAs, precursors thereto, targets thereof and related sequences. Such nucleic acids are useful for diagnostic purposes, and also for modifying target gene expression (e.g., paragraph 4th, column 4). Bentwich teaches that Human Herpes virus 1 and 2 are related to any of several inflammatory diseases caused by a herpesvirus and marked in one case by groups of watery blisters on the skin or mucous membranes (e.g., paragraph 5th, column 20). Bentwich teaches SEQ ID NO 539856 that has 100% homology with SEQ ID NO 372 of the instant claim..
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use the polynucleotide SEQ ID NO 539856 taught by Bentwich and to integrate in the composition for treating or preventing a herpesvirus infection taught by Roehm, for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of obtaining a composition for treating or preventing a herpesvirus infection comprising a) a CRISPR-associated (Cas) peptide and b) an isolated guide nucleic acid to target herpes virus 1 genes.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a composition comprising a CRISPR-associated (Cas) peptide or an isolated nucleic acid encoding a Cas peptide; and an isolated guide nucleic acid complementary to a target sequence in the herpesvirus genome for treating or preventing a herpesvirus infection.
Claims 111-113 are rejected under 35 U.S.C. 103 as being unpatentable over Roehm et al. (“Roehm”, US 2018/0000970 A1) as applied to claims 104-105, 107-110 above, and further in view of Maeder et al. (“Maeder”, WO 2015/153789 A1).
Roehm does not teach a four guide targeting ICP27 gene, as required by instant claims 111-112. Roehm does not teach the second and third guide RNAs targeting ICP27 as required by instant claim 113. However, this is cured by Maeder.
Maeder teaches methods and compositions for the treatment or prevention of herpes simplex virus type 1 (HSV-1), which causes intermittent sores of the mouth and mucous membranes (e.g., paragraph 3rd, page 3). Maeder teaches methods and compositions to alter one or more of UL19, UL30, ULA8 and/or UL54 (encodes ICP27) gene(s) to treat or prevent HSV-1 by targeting the gene, e.g., the non-coding or coding regions, e.g., the promoter region, or a transcribed sequence, e.g., intronic or exonic sequence (e.g., paragraph 4th, page 3). Maeder multiple gRNAs are used to generate (1) two single stranded breaks in close proximity, (2) two double stranded breaks, e.g., flanking a HSV-1 target position (e.g., to remove a piece of DNA, e.g., to create a deletion mutation) or to create more than one indel in the gene, e.g., in a coding region, e.g., an early coding region, (3) one double stranded break and two paired nicks flanking a HSV-1 target position (e.g., to remove a piece of DNA, e.g., to insert a deletion) or (4) four single stranded breaks, two on each side of a position, that they are targeting the same HSV-1 target position (e.g., paragraph 3rd, page 7). Maeder teaches first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule (e.g., paragraph 2nd, page 7). Maeder teaches targeting domains for knocking out the UL54 gene
selected according to the second tier parameters. The targeting domains are selected based on location within the first 500bp of the coding sequence of the UL54 (ICP27) gene (the gRNAs target different positions ion ICP27 gene) (e.g., paragraph 1st, page 270; Table 4B).
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Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use a fourth gRNA molecule corresponding to a different ICP27 sequence taught by Maeder and to integrate in the composition for treating or preventing a herpesvirus infection taught by Roehm, for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of obtaining a composition for treating or preventing a herpesvirus infection comprising a CRISPR-associated (Cas) peptide and two gRNA (first and second) targeting ICP0 and two gRNAs (third and fourth gRNA) targeting ICP27 to target herpes virus 1 genome.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a composition comprising a CRISPR-associated (Cas) peptide or an isolated nucleic acid encoding a Cas peptide; and an two gRNAs targeting ICP0 gene and two gRNAs targeting ICP27 gene in the herpesvirus genome for treating or preventing a herpesvirus infection.
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use a third gRNA molecule corresponding to a different ICP27 sequence taught by Maeder and to integrate in the composition a combination therapy that includes a cocktail of gRNAs for targeting important viral proteins (ICP0 and ICP27) for treating or preventing a herpesvirus infection taught by Roehm, for someone skilled in the art would have been obvious to use these teachings to achieve the predictable result of obtaining a composition for treating or preventing a herpesvirus infection comprising a CRISPR-associated (Cas) peptide and first gRNA targeting ICP0 and two gRNAs (second and third gRNA) targeting ICP27 to target herpes virus 1 genome.
One of ordinary skill in the art before the effective filing date of the invention would have been motivated to do so in order to develop a composition comprising a CRISPR-associated (Cas) peptide or an isolated nucleic acid encoding a Cas peptide; and a first gRNA targeting ICP0 gene and two gRNAs targeting ICP27 gene in the herpesvirus genome for treating or preventing a herpesvirus infection.
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 104-105, 110, 113 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-7, 10-13 of copending Application No. 19081195 (“195”).
This is a provisional nonstatutory double patenting rejection.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims encompass those of the copending application: A CRISPR-Cas system comprising:(a) a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease; (b) a guide ribonucleic acid, wherein the guide ribonucleic acid comprises a spacer sequence that hybridizes to the reverse complement of the protospacer sequence of any one of SEQ ID NOs: 364-377. The CRISPR-Cas system of claim 104, wherein the spacer sequence comprises about 20 nucleotides. A composition comprising:(a) a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease or a nucleic acid sequence encoding the CRISPR-associated endonuclease; (b) a first guide nucleic acid or a nucleic acid sequence encoding the first guide nucleic acid, the first guide nucleic acid being complementary to a first target nucleic acid sequence within or near an ICPO gene of a herpesvirus genome;(c) a second guide nucleic acid or a nucleic acid sequence encoding the second guide nucleic acid, the second guide nucleic acid being complementary to a second target nucleic acid sequence within or near the ICPO gene of a herpesvirus genome; and (d) a third guide nucleic acid or a nucleic acid sequence encoding the third guide nucleic acid, the third guide nucleic acid being complementary to a third target nucleic acid sequence within or near an ICP27 gene of a herpesvirus genome; wherein the first target nucleic acid sequence, the second target nucleic acid sequence, and the third target nucleic acid sequence are different. A composition comprising:(a) a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease or a nucleic acid sequence encoding the CRISPR-associated endonuclease; (b) a first guide nucleic acid or a nucleic acid sequence encoding the first guide nucleic acid, the first guide nucleic acid being complementary to a first target nucleic acid sequence within or near an ICPO gene of a herpesvirus genome; (c) a second guide nucleic acid or a nucleic acid sequence encoding the second guide nucleic acid, the second guide nucleic acid being complementary to a second target nucleic acid sequence within or near and ICP27 gene of a herpesvirus genome; and (d) a third guide nucleic acid or a nucleic acid sequence encoding the third guide nucleic acid, the third guide nucleic acid being complementary to a third target nucleic acid sequence within or near the ICP27 gene of a herpesvirus genome; wherein the first target nucleic acid sequence, the second target nucleic acid sequence, and the third target nucleic acid sequence are different.
It is noted that “195” represent a species with regard to An expression vector comprising a nucleic acid sequence encoding:(a) a Cas protein; and(b) a first guide RNA (gRNA) and a second gRNA molecule,each gRNA comprising a nucleotide sequence substantially complementary to a different target sequence in a herpesvirus genome, the first gRNA comprising a spacer sequence of any one of SEQ ID NOs: 34, 35, or 36 or a fragment thereof and being substantially complementary to a first target sequence within an ICPO region of the herpesvirus genome, and the second gRNA being substantially complementary to a second target sequence within an ICP4 or an ICP27 region of the herpesvirus genome, see “195”, claim 1. The expression vector of claim 1, wherein the first gRNA or second gRNA comprise crRNA and tracrRNA, see “195”, claim 4. The expression vector of claim 1, wherein the herpesvirus is herpes simplex type I (HSV1), see “195” claim 5. The expression vector of claim 1, wherein the nucleic acid sequence encodes three or more gRNA molecules, see “195” claim 6. A pharmaceutical composition comprising:an expression vector comprising a nucleic acid sequence encoding:(a) a Cas protein; and(b) first guide RNA (gRNA) and a second gRNA molecule,each gRNA comprising a nucleotide sequence substantially complementary to a different target sequence in a herpesvirus genome, the first gRNA comprising a spacer sequence of any one of SEQ ID NOs: 34, 35, or 36 or a fragment thereof and being substantially complementary to a first target sequence within an ICPO region of the herpesvirus genome, and the second gRNA being substantially complementary to a second target sequence within an ICP4 or an ICP27 region of the herpesvirus genome, see “195” claim 7. The pharmaceutical composition of claim 6, wherein the first gRNA or the second gRNA comprises crRNA and tracrRNA, see “195” claim 10. The pharmaceutical composition of claim 6, wherein the herpesvirus is herpes simplex type I (HSV1), see “195” claim 11. The pharmaceutical composition of claim 6, wherein the nucleic acid sequence encodes 3 or more gRNA molecules, see “195” claim 12. A method of inactivating a viral deoxyribonucleic acid (DNA) sequence of a herpesvirus genome in a cell, the method comprising contacting the cell with a therapeutically effective amount of a composition comprising:(a) a Cas protein or a nucleic acid encoding a Cas protein; and(b) first guide RNA (gRNA) and a second gRNA molecule, each gRNA comprising a nucleotide sequence substantially complementary to a different target sequence in the herpesvirus genome, the first gRNA comprising a spacer sequence of any one of SEQ ID NOs: 34, 35, or 36 or a fragment thereof and being substantially complementary to a first target sequence within an ICPO region of the herpesvirus genome, and the second gRNA being substantially complementary to a second target sequence within an ICP4 or an ICP27 region of the herpesvirus genome, see “195” claim 13.
SEQ ID NO: 364-366 of the instant application are 100% homologous to SEQ ID NO 34, 35 and 36 of the copending application:
SEQ ID NO 364 vs SEQ ID 34:
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SEQ ID NO 365 vs SEQ ID 35:
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SEQ ID NO 366 vs SEQ ID 36:
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIO GOMEZ RODRIGUEZ whose telephone number is (571)270-0991. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 5712722916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/Examiner, Art Unit 1637
/J. E. ANGELL, Ph.D./Primary Examiner, Art Unit 1637