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 .
The preliminary amendment filed 1/22/2024 has been received and entered into the application file. Claims 104 and 127-152 are pending, all of which have been considered on the merits.
Priority
Acknowledgement is made of Applicants’ claim for benefit under 35 USC 121 as a divisional of prior-filed US application 16/925436 (now US Patent 11820969), which claims benefit under 35 USC 121 as a divisional of prior-filed US application 15/852891 (now US Patent 10745677), which claims benefit of prior-filed US Provisional application 62/438827 (filed 12/23/2016).
However, the instant application is an improper divisional of prior-filed application 16/925436. No restriction requirement was made in parent application 16/925436, thus claiming benefit under 35 USC 121 is improper. Applicants are required to correct the priority claim of the instant application by filing a new ADS, wherein under “domestic priority” the word “divisional” is lined through and the word “continuation” is written in and underlined. Applicants are not afforded the ‘121 shield’ over US Patent 11820969 (resulting from US application 16/925436).
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.
Claims 104 and 127-152 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 104: The composition contains a fusion protein comprising (b) a cytosine deaminase domain. However, it appears Applicants intend to claim a fusion protein comprising a (b) cytidine deaminase domain. The specification recites both terms, seemingly interchangeably, however they are different molecules. Cytosine deaminases target free cytosine, whereas cytidine deaminase targets the nucleoside cytidine, converting it to uridine. The specific examples of deaminase proteins disclosed (e.g. APOBECs listed in claim 139) are examples of cytidine deaminases. Use of cytosine deaminase in the claims renders the claims indefinite. Applicants should carefully review all claims and the specification for correction and consistency.
All claims depend directly or indirectly from claim 104, and many further use the term cytosine deaminase, and thus inherit the deficiency and are rejected on the same basis.
Regarding claim 132: There is insufficient antecedent basis for the limitation “the UGI domain” in line 1 of the claim. Claim 132 depends from claim 128, which does not require a UGI domain. Claim 127 requires a UGI domain, but Applicants are cautioned against changing dependency to claim 127, as claim 127 does not provide antecedent basis for “the dCas9 domain”.
Regarding claim 140: The claim requires the cytidine [sic: cytosine] deaminase to comprise an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 1-260, 270-292, or 315-323. However, the sequences in this list are not to deaminase sequences at all, but rather to Cas9 nucleotide sequences (See as-filed specification at ¶0078, 0262). SEQ ID NOs 1-260 and 315-323 are clearly described as Cas9 sequences. SEQ ID NOs 270-292 appear to be deaminase sequences (See ¶0263), but the specification refers to them as Cas9 sequences in multiple paragraphs (See ¶0078, 0134, etc). Clarification is required.
Regarding claim 142: Reference to “the guide nucleotide sequence” in line 1 of the claim renders the claim indefinite because parent claim 104 recites two guide nucleotide sequences:
a guide nucleotide sequence-programmable DNA binding protein domain as part of the (i) fusion protein, and
(ii) a guide nucleotide sequence targeting the fusion protein,
It is unclear which guide nucleotide sequence is being further limited.
Regarding claim 150: Claim 150 is directed to a method of reducing functional CCR5 receptors on a cell in a subject. The method requires administration of the composition of claim 144 to a subject in need thereof. It is unclear who would be in need of reduced functional CCR5 receptors. The specification does not clearly identify the metes and bounds of this patient population.
Claim Rejections - 35 USC § 103
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.
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 104 and 127-152 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2017/0121693).
The applied reference has one common inventor and assignee 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).
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.
Liu et al disclose fusion proteins comprising (i) a domain capable of binding to a nucleotide sequence (e.g. Cas9 or Cpf1), and (ii) an enzyme domain, specifically a deaminase domain. This fusion protein can be used to edit target nucleic acid sequences to correct gene defects or to introduce deactivating mutations in disease-associated genes (See ¶0180). Liu et al teaches inclusion of (iii) a UGI domain can further enhance the efficacy of the fusion protein on gene editing (See ¶0017, 0292-0315). Details on the (i) domain capable of binding to a nucleotide sequence are provided at ¶0181-0202. Details on the (ii) deaminase domain are provided at ¶0203-0210. Cytidine deaminases are disclosed.
Liu et al teach methods of using the fusion protein to cause gene edits. Specifically, the fusion protein is combined with at least one guide RNA that comprises a sequence that is complementary to a target sequence. The target sequence comprises a sequence associated with a disease or disorder. Contacting the DNA with the complex comprising the fusion protein and at least one guide RNA results in a point mutation in the target gene. The contacting can occur, inter alia, in vivo in a subject. The disease to be treated can be, inter alia, HIV (See ¶0316-0317).
In Example 2 (¶0349) Liu et al disclose the dCas9:deaminase fusion proteins described therein can be delivered to a cell in vitro or ex vivo, or to a subject in vivo to effect C to T or G to A transitions when the target nucleotide is in positions 3-11 with respect to a PAM. Liu et al teach several deamination targets, including several in the CCR5 gene (Q93, Q012, Q186, R225, W86, or Q261) which can be deaminated to generate a STOP codon which results in nonfunctional truncation of CCR5. Liu et al teaches this has application in HIV treatment (See ¶0349).
Regarding claims 104, 128, 131, 142 and 152: Example 2 of Liu et al, wherein the fusion protein is targeted to one of the codons encoding Q93, Q012, Q186, R225, W86, or Q261 in CCR5 is relied upon for this rejection.
Liu et al does not disclose the exact fusion protein used, rather they reference ‘dCas9:deaminase fusion protein described herein’. The generically described ‘dCas9:deaminase fusion protein’ reads on (i) a fusion protein. The dCas9 portion reads on (a) a guide nucleotide sequence-programmable DNA binding protein domain, specifically a dCas9. Though Liu et al does not explicitly describe the deaminase as a cytidine [sic: cytosine] deaminase, the disclosure at ¶0203-0210 makes it clear that the deaminase is a cytidine deaminase, intended to effect C to T point mutation. Therefore, it would have at least been prima facie obvious to have utilized a cytidine deaminase as the deaminase protein in the dCas9: deaminase fusion protein of Example 2.
Furthermore, while Liu et al does not explicitly recite the presence of a single guide nucleotide targeting a portion of the polynucleotide encoding CCR5, the fact that Liu et al teach the fusion protein is targeted to one of the codons encoding Q93, Q012, Q186, R225, W86, or Q261 in CCR5 implies that there is a single guide nucleotide sequence that will target the fusion protein to these particular sequences within the CCR5 gene. This inherently present guide nucleotide reads on (ii) a guide nucleotide sequence targeting the fusion protein of (i) to a polynucleotide encoding a CCR5 protein.
The composition comprising the (i) fusion protein and the (ii) guide nucleotide sequence satisfy the limitations of claim 104, 128, 131, 142 and the kit claim of claim 152.
Regarding claim 127: Following the discussion above, though Liu et al does not explicitly describe the presence of a UGI domain in the fusion protein used in Example 2, Liu et al teach the fusion proteins preferably further include a (c) UGI domain in order to improve gene editing efficacy (See ¶0017, 0292-0315). Therefore, it would have been prima facie obvious to have utilized a fusion protein of Liu et al that further comprised (c) UGI domain.
Regarding claims 132 and 137: Following the discussion of claim 127 above, Liu et al teach the UGI can be fused to the C-terminus of the dCas9 domain, a linker is optional (See ¶0299).
Regarding claim 138: Following the discussion of claim 127 above, Liu et al teach the fusion protein can have the various components in any order, with several variations shown in ¶0293-0304. Selection of any order of components is considered to have been prima facie obvious, as there were a finite number of orders which where possible, each expected to have similar results (based on the teachings of ¶0293-0304 of Liu et al).
Regarding claim 133-136: Following the discussion of claim 104 above, while Example 2 references a “dCas9:deaminase” fusion protein, Liu et al teach that the guide nucleotide sequence-programmable DNA binding protein domain (i.e. Cas9 domain) can be, inter alia, Cas9, Cas9 nickase, dCas9, or dCas9 domains having a D10X mutation relative to SEQ ID NO: 10 (SEQ ID NO: 10 is a 100% match to SEQ ID NO: 1 of the instant application; see appendix) (See ¶0181). It would therefore have been prima facie obvious to have substituted any of the disclosed Cas9 domains for the dCas9 domain in the fusion protein used in Example 2 with a reasonable expectation of success based on the disclosure in Liu et al of their functional equivalency.
Regarding claims 139-140: Following the discussion of claim 104 above, while Example 2 only generically refers to a “dCas9: deaminase” fusion protein, Liu et al clearly teach that the deaminase portion is a cytidine deaminase, and can be, inter alia, AID deaminase (See ¶0203). Liu et al teach human AID with SEQ ID NO: 266 (which is 100% identical to SEQ ID NO: 270 of instant application; see appendix). It would therefore have been prima facie obvious to have substituted any of the disclosed cytidine deaminase domains for the deaminase domain in the fusion protein used in Example 2 with a reasonable expectation of success based on the disclosure in Liu et al of their functional equivalency.
Regarding claim 141: Following the discussion of claim 104, while Example 2 only generically refers to a “dCas9: deaminase” fusion protein, Liu et al teaches the fusion protein can have SEQ ID NO: 594 (See claim 25). SEQ ID NO: 594 has 97.6% identity to SEQ ID NO: 293 of the instant application (see appendix). As above, while not exemplified in Example 2, it would have been prima facie obvious to have used the specific fusion protein taught elsewhere in Liu et al in the method of Example 2. This is based on the fact that Liu et al teach the fusion peptide having SEQ ID NO: 594 is appropriate to achieve the point mutation desired.
Regarding claim 143: Following the discussion of claim 104 above, Example 2 states the fusion protein can be targeted to one of the codons encoding Q93, Q012, Q186, R225, W86, or Q261.
Regarding claims 144-151: Following discussion of claim 104 above, Example 2 states that the ‘dCas9:deaminase’ fusion protein can be delivered to a subject for the treatment of HIV. Official notice is taken that for delivery of a protein to a subject, inclusion within a pharmaceutically acceptable carrier is required. Thus, it would have been at least prima facie obvious to have provided the fusion protein within a pharmaceutically acceptable carrier. Furthermore, administration to a subject having or at risk of having HIV will satisfy the limitations of each of claims 145-151, noting that the effects of the fusion protein targeting CCR5 gene recited in alims 145-151 would be inherent.
Claims 104, 128-131, 133-136, and 139-152 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 2015/0166982), in view of Maeder et al (WO 15/148670).
Liu et al disclose fusion proteins comprising (i) a nuclease-inactive Cas9 domain; and (ii) a nuclease acid editing domain, specifically a cytidine deaminase domain (See ¶0008). Liu et al further disclose systems comprising (a) the above described fusion protein, and (b) an sgRNA targeting the fusion protein to a target nucleotide sequence of a DNA strand in need of editing. The target nucleotide sequence of the DNA strand can be a sequence associated with a disease or disorder. Liu et al teach contacting of the DNA strand with the system to cause deamination of a nucleotide base at the target nucleotide sequence, wherein the deamination has a therapeutic effect on the disease or disorder (See ¶0009).
Regarding claims 104, 128, 131, 142, 143 and 152: The system of Liu et al is comparable to the currently claimed composition as it contains a fusion protein comprising a nuclease-inactive Cas9 domain and a cytidine deaminase (which reads on the (i) fusion protein of current claims 104, 128, and 131). The (b) sgRNA targeting the (a) fusion protein to a target nucleotide sequence of a DNA is comparable to (ii) a guide nucleotide sequence (sgRNA) of current claim 104.
The system of Liu et al differs from the composition of current claim 104 in that, while Liu et al gives examples of several diseases or disorders that can be treated by their mechanism, they do not specifically teach a disease associated with CCR5. Thus, Liu et al does not teach an embodiment wherein the (b) sgRNA would target the fusion protein to a target nucleotide sequence in the CCR5 gene.
However, Maeder et al teach that inactivation of the CCR5 gene is effective for treatment and prevention of HIV, as the HIV relies on CCR5 for entry into T cells (See Pg 2, ln 28-31 and Pg 3, ln 15-18). Maeder et al also evidences that there was motivation to treat and prevent HIV and AIDs in the human population.
It would have been prima facie obvious to have modified the system of Liu et al to have chosen an sgRNA that would specifically target the fusion protein to a target sequence within the CCR5 gene. One would have been motivated to have made this modification in order to deaminate a cytosine in the CCR5 gene, thereby deactivating the CCR5 gene, thereby treating or preventing HIV in subjects in need thereof. One would have had a reasonable expectation of success because Liu et al teach the system will deliver the fusion protein to a targeted sequence on DNA and will deaminate cytosine, and because Maeder et al disclose numerous gRNA molecules that will target various locations within the CCR5 gene (See, e.g. the sequences listed in Tables 1A-1F). Thus there was a reasonable expectation that using one of the gRNA molecules of Maeder et al in the system of Liu et al would serve to edit the CCR5 gene. It is specifically noted that the first gRNA listed in Table 1A, CCR5-66 (SEQ ID NO: 387) is 100% identical to SEQ ID NO: 417 of the instant application (See appendix).
Thus, the modified system meets the limitation of current claims 104, 128, 131, 142, 143 and the ‘kit’ of claim 152.
Regarding claims 128-130: Official notice is taken that dCas9, dCpf1 and dAgo domains were art recognized alternatives for nucleic acid-guided endonucleases useful in gene editing. Selection of any one of the three would have been prima facie obvious on the basis of substituting one known element for another in the fusion protein of Liu et al.
Regarding claims 134-136: Following the discussion of claim 104 above, Liu et al teach Cas9 domain of the fusion protein can be other known nuclease-inactive Cas9 variants, including D10A/H840A variants, such as that of SEQ ID NO: 37 (See ¶0038). SEQ ID NO: 37 is 100% identical to SEQ ID NO: 2 of the instant application (which is the Cas9 nickase with D10A and H840A mutation relative to SEQ ID NO: 1; see appendix).
Regarding claims 139-140: Following the discussion of claim 104 above, Liu et al teaches the cytidine deaminase can be human AID, having SEQ ID NO: 6 (See ¶0058), which is 100% identical to SEQ ID NO: 270 of the instant application (See appendix).
Regarding claim 141: Following the discussion of claim 104 above, Liu et al provide as an exemplary fusion protein SEQ ID NO: 30 (See ¶0097). The fusion protein of SEQ ID NO: 30 is 82.5% identical to SEQ ID NO: 293 of the instant application (see appendix).
Regarding claims 144-151: Following discussion of claim 104 above, given that the modified fusion protein system of Liu et al is modified to target CCR5, for the purpose of treating or preventing HIV, it would have been prima facie obvious to have administered the system comprising the fusion to a subject in need of treatment of prevention of HIV. Official notice is taken that for delivery of a protein to a subject, inclusion within a pharmaceutically acceptable carrier is required. Furthermore, administration to a subject having or at risk of having HIV will satisfy the limitations of each of claims 145-151, noting that the effects of the fusion protein targeting CCR5 gene recited in alims 145-151 would be inherent.
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 and 127-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10745677.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate and/or render obvious the instant claims.
Regarding claims 104, 127 and 152: Patented claim 1 is drawn to a method that uses the composition of current claim 127. The fact that the method uses the composition means the patented claims anticipate the product, per se. It is noted that the patent claim recites cytosine deaminase, which is the same term used in the current claims. However, for the reasons set forth under 35 USC 112(b), it appears this was a misnomer for cytidine deaminase.
Regarding claims 128, 129, 130 and 131: Patented claim 6 teaches the additional limitations.
Regarding claim 132: Patented claim 20 teaches the additional limitations.
Regarding claim 133-136: Patented claim 5 teaches the additional limitations.
Regarding claim 137-138: Patented claim 21 teaches the additional limitations.
Regarding claim 139: Patented claim 22 teaches the additional limitations.
Regarding claim 140: Patented claim 23 teaches the additional limitations.
Regarding claim 141: Patented claim 24 teaches the additional limitations.
Regarding claim 142: Patented claim 25 teaches the additional limitations.
Regarding claim 143: Patented claim 143 teaches the additional limitations.
Regarding claim 144: Inclusion of a pharmaceutically acceptable carrier is considered prima facie obvious, and actually necessary, for delivery/use of any chemical molecule.
Regarding claims 145-151: Performing the method of patented claim 1 will modify the CCR5 protein such that binding capacity between gp120 and CCR5 is reduced. According to the patent specification, this will treat and/or prevent immunologic diseases, including HIV and AIDS. It would therefore have been prima facie obvious to have administered the (i) fusion protein and (ii) guide nucleotide sequence targeting the fusion protein (as in patented claim 1) to a subject for the purpose of causing the CCR5 editing in vivo. Administration of the (i) fusion protein and (ii) guide nucleotide sequence targeting the fusion protein will inherently achieve the effects of claims 145-151.
Claims 104, 127 and 152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 11820969.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate and/or render obvious the instant claims.
Regarding claims 104, 127 and 152: Patented claim 27 discloses a composition that anticipates the composition of current claims 104, 127 and 152. It is noted that the patent claim recites cytosine deaminase, which is the same term used in the current claims. However, for the reasons set forth under 35 USC 112(b), it appears this was a misnomer for cytidine deaminase.
Regarding claim 144: Inclusion of a pharmaceutically acceptable carrier is considered prima facie obvious, and actually necessary, for delivery/use of any chemical molecule.
Claims 104 and 127-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10167457, in view of Maeder et al (WO 15/148670).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims as follows: Regarding claims 104, 127, 128 and 131: Patented claim 1 is to a fusion protein which anticipates the fusion protein portion of the composition of current claims 104, 127, 128 and 131. The patented claim differs in that it does not specifically include a guide nucleic acid that targets the fusion protein to a CCR5 protein. However, patented claim 23 is to a complex comprising the fusion protein of claim 1, and further including a guide RNA.
None of the patented claims specify the guide RNA targets the fusion protein to a CCR5 protein. However, at the time the application was filed, Maeder et al taught that introducing mutations into the CCR5 gene can help treat and prevent HIV. The teachings of Maeder et al are set forth above. It would have been prima facie obvious to have modified the complex of patent claim 23 to have chosen an guide RNA that would specifically target the fusion protein to a target sequence within the CCR5 gene. One would have been motivated to have made this modification in order to deaminate a cytosine in the CCR5 gene, thereby deactivating the CCR5 gene, thereby treating or preventing HIV in subjects in need thereof. One would have had a reasonable expectation of success because the patented system will deliver the fusion protein to a targeted sequence on DNA and will deaminate cytosine, and because Maeder et al disclose numerous gRNA molecules that will target various locations within the CCR5 gene (See, e.g. the sequences listed in Tables 1A-1F). Thus there was a reasonable expectation that using one of the gRNA molecules of Maeder et al in the patented complex/system would serve to edit the CCR5 gene. It is specifically noted that the first gRNA listed in Table 1A, CCR5-66 (SEQ ID NO: 387) is 100% identical to SEQ ID NO: 417 of the instant application (See appendix).
The remaining patent claims teach the features of the fusion protein required by dependent claims 132-143.
Regarding claims 144-151: Following discussion of claim 104 above, given that the fusion protein system of the patented claims, modified to target CCR5, for the purpose of treating or preventing HIV, it would have been prima facie obvious to have administered the system comprising the fusion to a subject in need of treatment of prevention of HIV. Official notice is taken that for delivery of a protein to a subject, inclusion within a pharmaceutically acceptable carrier is required. Furthermore, administration to a subject having or at risk of having HIV will satisfy the limitations of each of claims 145-151, noting that the effects of the fusion protein targeting CCR5 gene recited in alims 145-151 would be inherent.
Claims 104 and 127-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. 12344869, in view of Maeder et al (WO 15/148670).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims as follows: Regarding claims 104, 127, 128 and 131: Patented claim 1 is to a composition comprising a fusion protein which anticipates the fusion protein portion of the composition of current claims 104, 127, 128 and 131. Patented claim 1 further comprises a guide RNA.
None of the patented claims specify the guide RNA targets the fusion protein to a CCR5 protein. However, at the time the application was filed, Maeder et al taught that introducing mutations into the CCR5 gene can help treat and prevent HIV. The teachings of Maeder et al are set forth above. It would have been prima facie obvious to have modified the complex of patent claim 23 to have chosen an guide RNA that would specifically target the fusion protein to a target sequence within the CCR5 gene. One would have been motivated to have made this modification in order to deaminate a cytosine in the CCR5 gene, thereby deactivating the CCR5 gene, thereby treating or preventing HIV in subjects in need thereof. One would have had a reasonable expectation of success because the patented system will deliver the fusion protein to a targeted sequence on DNA and will deaminate cytosine, and because Maeder et al disclose numerous gRNA molecules that will target various locations within the CCR5 gene (See, e.g. the sequences listed in Tables 1A-1F). Thus there was a reasonable expectation that using one of the gRNA molecules of Maeder et al in the patented complex/system would serve to edit the CCR5 gene. It is specifically noted that the first gRNA listed in Table 1A, CCR5-66 (SEQ ID NO: 387) is 100% identical to SEQ ID NO: 417 of the instant application (See appendix).
The remaining patent claims teach the features of the fusion protein required by dependent claims 132-143.
Regarding claims 144-151: Following discussion of claim 104 above, given that the fusion protein system of the patented claims, modified to target CCR5, for the purpose of treating or preventing HIV, it would have been prima facie obvious to have administered the system comprising the fusion to a subject in need of treatment of prevention of HIV. Official notice is taken that for delivery of a protein to a subject, inclusion within a pharmaceutically acceptable carrier is required. Furthermore, administration to a subject having or at risk of having HIV will satisfy the limitations of each of claims 145-151, noting that the effects of the fusion protein targeting CCR5 gene recited in alims 145-151 would be inherent.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
APPENDIX: Sequence Alignment
Qy: SEQ ID NO: 1 (instant application) vs Db: SEQ ID NO: 10 (US 2017/0121693A1)
PNG
media_image1.png
230
657
media_image1.png
Greyscale
Qy: SEQ ID NO: 270 (instant application) vs Db: SEQ ID NO: 266 (US 2017/0121693A1)
PNG
media_image2.png
248
736
media_image2.png
Greyscale
Qy: SEQ ID NO: 293 (instant application) vs Db: SEQ ID NO: 594 (US 2017/0121693A1)
PNG
media_image3.png
311
670
media_image3.png
Greyscale
Qy: SEQ ID NO: 417 (instant application) vs Db: SEQ ID NO: 387 (US 2015/0166982A1)
PNG
media_image4.png
190
782
media_image4.png
Greyscale
Qy: SEQ ID NO: 270 (instant application) vs Db: SEQ ID NO: 6 (US 2015/0166982A1)
PNG
media_image5.png
262
662
media_image5.png
Greyscale
Qy: SEQ ID NO: 2 (instant application) vs Db: SEQ ID NO: 37 (US 2015/0166982A1)
PNG
media_image6.png
331
720
media_image6.png
Greyscale
Qy: SEQ ID NO: 293 (instant application) vs Db: SEQ ID NO: 30 (US 2015/0166982A1)
PNG
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277
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Prosecution Insights