Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-9 are under consideration in the instant Office Action.
Information Disclosure Statement
The information disclosure statement filed 1/30/2024 fails to fully comply with 37 CFR 1.98(a)(3) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each patent listed that is not in the English language. The citations have therefore been lined through and have not been considered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3 and 6-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Donsante et al., WO2017/136202 (IDS, 1/30/2024).
Donsante teaches methods of treating brain disorders using adeno-associated virus gene therapy vectors with a gene product of interest flanked by AAV ITRs (see page, 2, lines 10-34, page 26, lines 13-34). Donsante teaches that the disease includes Type II Gaucher’s disease with the treatment of glucocerebrosidase (see bottom of page 37 and top of page 38 and claim 1) and reads on instant claim 1. It is noted that while the reference does not specifically teach the nucleotide sequence of SEQ ID NO:15, it clear that the requirement of glucocerebrosidase meets this requirement since it is the same product. It is clear that the same glucocerebrosidase would have the same characteristics as the instantly claimed composition since there is no evidence to the contrary. Note that rejections for anticipation are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not the same or an obvious variant; see MPEP § 2112(V). Donsante teaches that the composition includes AAV9 capsid proteins (see page 25, lines 29-34, page 26, lines 13-34, page 28, lines 11-18) and reads on instant claim 1. Donsante teaches using AAV ITRS serotype 2 ITRs including wildtype (see page 11, lines 1-5, page 25, lines 12-27, page 26, last paragraph) and reads on instant claims 6-7. Donsante teaches the AAVs to include chicken beta action (CBA) promotor and cytomegalovirus (CMV) enhancer flanked by inverted terminal repeats of AAV2 (see page 42, lines 5-10) and reads on instant claims 2-3. Donsante teaches that the vector is in a formulation composed of 20mM Tris pH8.0, 1mM MgCL2, 200mM Nacl and 0.001% Pluronic F68 (aka poloxamer 188) (see page 43, lines 12-13) and reads on instant claim 1.
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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Blits US2016/0243260 (IDS, 1/30/2024) and Donsante et al., WO2017/136202 (IDS, 1/30/2024) in view of Francois et al., 2005 (IDS, 1/30/2024).
See Donsante, as discussed above. Donsante does not teach the rAAV comprising a TRY region comprising SEQ ID NO:28.
Blits teaches methods of treating brain disorders using adeno-associated virus (AAV) gene therapy vectors with a gene product of interest flanked by AAV ITRs (see abstract). Blits teaches that the disease includes Type II Gaucher’s disease with the treatment of glucocerebrosidase (see Table 1, page 7 and paragraphs 12, 62, 67) and reads on instant claim 1. It is noted that while the reference does not specifically teach the nucleotide sequence of SEQ ID NO:15, it clear that the requirement of glucocerebrosidase meets this requirement since it is the same product. Blits teaches that the composition includes AAV9 capsid proteins (see paragraphs 38-39, 47) as required in instant claims 1 and 9. Blits teaches using AAV ITRS serotype 2 ITRs including wildtype (see paragraphs 11, 39, 47) as in instant claims 6-7. Blits teaches the AAVs to include chicken beta action (CBA) promotor, cytomegalovirus (CMV) enhancer, Woodchuck Hepatitis Virus Posttranscriptional Regulator Element (WPRE) and Bovine Growth Hormone polyA signal tail flanked by inverted terminal repeats of AAV2 (see paragraphs 66 and 101) and reads on instant claims 2-7 and 9. Blits teaches that 5’ to ‘3 order of the vector (see paragraph 23) of instant claims 6 and 9. Blits teaches that 5’ to ‘3 order of the vector (see page 16, lines 1-5) of instant claims 6 and 9
Neither Blits nor Donsante teach the rAAV comprising a TRY region comprising SEQ ID NO:28. It is noted that the instant specification, at paragraph 142, teaches that the TRY region, composed of TATA, RBS and YY1, and set forth in the SEQ ID NO:28 of claim 8 is taught in the Francois et al., 2005 (IDS, 1/30/2024).
Francois defines the minimal elements within the p5 region required for Rep-dependent replication. Francois teaches assays performed in transfected cells (in vivo) indicated that the minimal p5 element was composed by a 55-bp sequence (nucleotides 250 to 304 of wild-type AAV-2) containing the TATA box, the Rep binding site, the terminal resolution site present at the transcription initiation site (trs+1), and a downstream 17-bp region that could potentially form a hairpin structure localizing the trs+1 at the top of the loop (see abstract). Francois teaches that the best result in rAAV vectors contained TATA, RBS and YY1 for in vivo expression (see paragraphs in pages 11082-11083).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Blits, Donsante and Francois. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because the TRY region in an rAAV vector as taught by Francois would increase its expression in vivo. Therefore, one of ordinary skill in the would want to use the teaching of Francois, the TRY region, in the vectors taught by Blits and Donsante to improve the in vivo expression of these vectors. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
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 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 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,4,7-15,18-19 and 23 of U.S. Patent No.11,903,985. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘985 claims a method that requires the same product of the instant claims. ‘985 claims the composition of a rAAV comprising:
(i) a rAAV vector comprising a nucleic acid comprising, in 5′ to 3′ order:
(a) an AAV2 ITR;
(b) a CMV enhancer;
(c) a CBA promoter;
(d) a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO: 15;
(e) a WPRE;
(f) a Bovine Growth Hormone polyA signal tail; and
(g) an AAV2 ITR; and
(ii) an AAV9 capsid protein as in instant claims 1-9.
‘985 also claims the formulation comprising about 20 mM Tris, pH 8.0, about 1 mM MgCl2, about 200 mM NaCl, and about 0.001% w/v poloxamer 188 and rAAV vector further comprises a TRY region between the 5′ ITR and the expression construct, wherein the TRY region comprises SEQ ID NO: 28.
Claims 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12,571,002 in view of Donsante et al., WO2017/136202 (IDS, 1/30/2024).
‘002 claims an isolated nucleic acid comprising an expression construct a rAAV comprising:
(i) a rAAV vector comprising a nucleic acid comprising, in 5′ to 3′ order:
(a) an AAV2 ITR;
(b) a CMV enhancer;
(c) a CBA promoter;
(d) a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO: 15;
(e) a WPRE;
(f) a Bovine Growth Hormone polyA signal tail; and
(g) an AAV2 ITR; and
(ii) an AAV9 capsid protein as in instant claims 1-9.
‘002 also claims that the rAAV vector further comprises a TRY region between the 5′ ITR and the expression construct, wherein the TRY region comprises SEQ ID NO: 28. ‘002 fails to claim the formulation comprising about 20 mM Tris, pH 8.0, about 1 mM MgCl2, about 200 mM NaCl, and about 0.001% w/v poloxamer 188.
Donsante teaches that the rAAV vector is in a formulation composed of 20mM Tris pH8.0, 1mM MgCL2, 200mM Nacl and 0.001% Pluronic F68 (aka poloxamer 188) (see page 43, lines 12-13).
Therefore, one of ordinary skill would be motivated to use rAAV vector taught by ‘002 in the formulation taught by Donsante since they also teach the same rAAV vector with a reasonable expectation of success.
Claims 1-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44-50 and 53-60 of copending Application No. 16/689,865 in view of in view of Donsante et al., WO2017/136202 (IDS, 1/30/2024).
‘865 claims an expression construct comprising a rAAV comprising:
(i) a rAAV vector comprising a nucleic acid comprising, in 5′ to 3′ order:
(a) an AAV2 ITR;
(b) a CMV enhancer;
(c) a CBA promoter;
(d) a transgene insert encoding a Gcase protein, wherein the transgene insert comprises the nucleotide sequence of SEQ ID NO: 15;
(e) a WPRE;
(f) a Bovine Growth Hormone polyA signal tail; and
(g) an AAV2 ITR; and
(ii) an AAV9 capsid protein as in instant claims 1-9.
‘865 also claims that the rAAV vector further comprises a TRY region between the 5′ ITR and the expression construct, wherein the TRY region comprises SEQ ID NO: 28. ‘865 fails to claim the formulation comprising about 20 mM Tris, pH 8.0, about 1 mM MgCl2, about 200 mM NaCl, and about 0.001% w/v poloxamer 188.
Donsante teaches that the rAAV vector is in a formulation composed of 20mM Tris pH8.0, 1mM MgCL2, 200mM Nacl and 0.001% Pluronic F68 (aka poloxamer 188) (see page 43, lines 12-13).
Therefore, one of ordinary skill would be motivated to use rAAV vector taught by ‘865 in the formulation taught by Donsante since they also teach the same rAAV vector with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Advisory Information
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to AURORA M. FONTAINHAS whose telephone number is 571-272-2952. The examiner can normally be reached on Monday - Friday (8AM - 4PM).
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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