DETAILED ACTION
Claims 1, 3-4, 6-12, 14-18, 21, 25, 27-28, 30-31, 33-35, and 38-39 are pending and under examination in the instant application.
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 Objections
Claims 1, 3-4, 6, 8, 11, 12, 14, 15, 21, 25, 27, 28, 30, 38, 39 objected to because of the following informalities:
Claims 1 and 25 recite the abbreviations NGLY1, ICV, and CNS.
Claims 3, 12, 27, and 38 recite the abbreviation NGLY1.
Claims 4, 15, and 28 recite the abbreviation CAG.
Claim 6, 30 recite the abbreviation WPRE-Mut6.
Claim 8 recites the abbreviation AAV2 ITRs.
Claim 11 recites the abbreviations GNA and CSF.
Claim 14 and 21 recite the abbreviations NGLY1 and CNS.
Claim 15 recites the abbreviations CAG, WPRE-Mut6, and AAV2 ITRs.
Claim 39 recites the abbreviation ICV.
The full terms should precede these abbreviations at the first iteration. While all abbreviations are noted
above, the claims must only be amended to spell out the entire word before the first use of the abbreviation.
Appropriate correction is required.
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.
Claim(s) 1, 4, 6-9, 12, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Scaria et al. (US20170096683A1, filed on 05/02/2015, and published on 04/06/2017).
Regarding claim 1, Gao et al. teaches a method of treating a subject having NGLYl deficiency (page 1, lines 22-23). The method involves administering to the subject an effective amount of an rAAV comprising a capsid containing a nucleic acid engineered to express NGLYl, e.g., in the central nervous system (CNS) of a subject (page 1, lines 24-26). The rAAV comprises an artificial transcription element that is operably linked to a transgene encoding NGLYl (page 18, lines 10-14). Gao et al. further teaches that the administration is by intrathecal injection (claim 13 of Gao et al.).
However, Gao et al. fails to teach administering to the subject the effective amount of an rAAV comprising the nucleic acid construct comprising a transgene encoding NGLY1 by ICV administration or via the cisterna magna.
However, Scaria et al. teaches methods for treating disorders of the CNS with improved compositions of rAAV particles comprising administering a recombinant adeno-associated virus (rAAV) particle to the subretina of the individual, wherein the administration is intracerebroventricular injection (ICV) into at least one cerebral lateral ventricle (Abstract and claims 126 and 136).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have modified the administration method of the nucleic acid construct comprising a transgene encoding NGLY1 of Gao et al. and substituted the intrathecal injection with intracerebroventricular injection as both intrathecal and intracerebroventricular injections are functional equivalents that can be used for administration, such as administering an effective amount of an rAAV comprising a nucleic acid construct comprising a transgene encoding NGLY1. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Regarding claim 4: Following discussion of claim1 above, Gao et al. further teaches that the nucleic acid encoding a NGLY 1 protein is generally operably linked to a promoter, wherein the promoter is a constitutive promoter, for example a chicken beta-actin (CAG) promoter (page 7, lines 17-20).
Regarding claim 6: Following discussion of claim1 above, Gao et al. further teaches that the nucleic acid sequence further comprises a woodchuck hepatitis vims posttranscriptional regulatory element (WPRE) (page 10, lines 7-10) and a rabbit beta- globulin poly A signal sequence (page 10, lines 4-5).
Regarding claim 8: Following discussion of claim1 above, Gao et al. further teaches that the nucleic acid construct is flanked by AAV2 ITRs (page 12, lines 5-6).
Regarding claim 9: Following discussion of claim 1 above, Gao et al. further teaches that the nucleic acid comprises the sequence as set forth in SEQ ID NO: 1, which is 100% identical to instant SEQ ID NO: 9 at positions 1123-1182 (please see below a screenshot of the Query match).
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Regarding claim 12: Following discussion of claim1 above, Gao et al. further teaches that after said administration there is a reduction or amelioration in one or more symptoms of NGLY1 deficiency in said patient relative to the symptom in the patient prior to said administration. Gao et al. further teaches that alleviating a disease associated with low levels of NGLY1 expression (e.g., NGLY1 Deficiency) includes delaying the development or progression of the disease, or reducing disease severity, such that this delay can be of varying lengths of time that are sufficient to give a statistically significant result (page 30, lines 17-22 and 23-25 and page 31, lines 1-2).
However, Gao et al. fails to specifically teach that the reduction or amelioration in the symptoms occur within at least 5 to 30 weeks after administration.
However, it would have been prima facie obvious to one of the ordinary skills in the art before the effective
filing date of the claimed invention to have specified the number of weeks between at least 5 to 30 weeks after which the reduction or amelioration in the symptoms of NGLY1 deficiency occur after the administration of the nucleic acid with a reasonable expectation of success. One would have been motivated to have optimized the length of time in the method taught by Gao et al. to give a statistically significant result in alleviating the disease.
Regarding claim 16: Following discussion of claim 1 above, Gao et al. further teaches that the nucleic acid comprises the sequence as set forth in SEQ ID NO: 1, which is 100% identical to instant SEQ ID NO: 8 at positions 985-1044 (please see below a screenshot of the Query match).
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Claim(s) 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Scaria et al. (US20170096683A1, filed on 05/02/2015, and published on 04/06/2017) as applied to claim 1 above and further in view of Alberts, et al. (Alberts, et al., "Molecular Biology of the Cell, Fifth Edition". New York:Garland Science, 2008. Pages 1-3 and 367).
Regarding claim 1, the teachings of Gao et al. and Scaria et al. are set forth in detail above.
Regarding claim 3: Following discussion of claim 1 above, Gao et al. further teaches that the nucleic acid comprises the sequence as set forth in SEQ ID NO: 1, which is 99.8% similar to instant SEQ ID NO: 1 (please see below a screenshot of the Query match, wherein the sequences only differ at the nucleotide at position 93 (A vs. C)).
However, Gao et al. in view of Scaria et al. fail to teach that the NGLY1 coding sequence is 100% identical to SEQ ID NO: 1.
However, Alberts, et al. teaches that both GCA and GCC codons encode for the same amino acid (Ala) (page 367, Figure 6-50).
Based on the teachings of Gao et al. of a similar nucleotide sequence encoding the NGLY1 coding sequence and the teachings of Alberts et al. that both GCA and GCC codons encode for the same amino acid (Ala), 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 have used the nucleotide sequence of the nucleic acid of SEQ ID NO: 1 taught by Gao et al. and modified it to substitute the (C) nucleotide at position 93 of SEQ ID NO: 1 for (A) nucleotide as this modification represents nothing more than the substitution of one codon of the nucleotide sequence for another that encodes for the same amino acid with predictable results.
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Claim(s) 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Scaria et al. (US20170096683A1, filed on 05/02/2015, and published on 04/06/2017) as applied to claim 1 above and further in view of Nolte et al. (US20210139563A1, filed on 05/02/2019, and published on 05/13/2021).
Regarding claim 1, the teachings of Gao et al. and Scaria et al. are set forth in detail above.
Regarding claim 10: Following discussion of claim 1 above, Gao et al. further teaches that the rAAV is an AAV9 capsid (claim 14 of Gao et al.).
However, Gao et al. in view of Scaria et al. fail to teach that the rAAV has a capsid that is at least 95% identical to SEQ ID NO: 10 (AAV9 sequence).
However, Nolte et al. teaches an AAV9 serotype sequence of SEQ ID NO: 59, which is 100% identical to instant SEQ ID NO: 10 (please see below a screenshot of the Query match).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have substituted the amino acid sequence of Gao et al. with the AAV9 serotype sequence of SEQ ID NO: 59 of Nolte et al. as this substitution represents nothing more than the substitution of one amino acid sequence with another with predictable results.
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Claim(s) 14, 15, 17, 18, 21, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Alberts, et al. (Alberts, et al., "Molecular Biology of the Cell, Fifth Edition". New York:Garland Science, 2008. Pages 1-3 and 367).
Regarding claims 14 and 21, Gao et al. teaches an rAAV comprising an AAV9 capsid containing a nucleic acid construct comprising the codon optimized nucleotide sequence encoding human NGLY1 of SEQ ID NO: 1 operably linked to regulatory elements such that the NGLY1 is expressed in the CNS of the subject (claims 1, 14, and 17 of Gao et al.). The nucleic acid sequence encoding NGLY1 is a codon-optimized sequence (claim 40 of Gao et al.). Gao et al. also teaches a host cell comprising an isolated nucleic acid encoding the NGLY1 protein (claim 44 of Gao et al.). Gao et al.’s SEQ ID NO: 1 is 99.8% similar to instant SEQ ID NO: 1 (please see above under the discussion of claim 3, a screenshot of the Query match, wherein the sequences only differ at the nucleotide at position 93 (A vs. C)).
However, Gao et al. fails to teach that the NGLY1 coding sequence is 100% identical to SEQ ID NO: 1.
However, Alberts, et al. teaches that both GCA and GCC codons encode for the same amino acid (Ala) (page 367, Figure 6-50).
Based on the teachings of Gao et al. of a similar nucleotide sequence encoding the NGLY1 coding sequence and the teachings of Alberts et al. that both GCA and GCC codons encode for the same amino acid (Ala), 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 have used the nucleotide sequence of the nucleic acid of SEQ ID NO: 1 taught by Gao et al. and modified it to substitute the (C) nucleotide at position 93 of SEQ ID NO: 1 for (A) nucleotide as this modification represents nothing more than the substitution of one codon of the nucleotide sequence for another that encodes for the same amino acid with predictable results.
Regarding claim 15: Following discussion of claim 14 above, Gao et al. further teaches that the nucleic acid sequence further comprises a CAG promoter, a chimeric intron (page 7, lines 17-20 and page 9, line 24), a woodchuck hepatitis vims posttranscriptional regulatory element (WPRE) (page 10, lines 7-10) and a rabbit beta- globulin poly A signal sequence (page 10, lines 4-5).
Regarding claims 17 and 38: Following discussion of claim 14 above, Gao et al. further teaches a pharmaceutical composition comprising the rAAV (claim 42 of Gao et al.).
Regarding claim 18: Following discussion of claim 17 above, Gao et al. further teaches that the pharmaceutical composition comprises phosphate buffered saline (page 19, lines 31-32). Gao et al. also teaches that rAAV compositions are formulated to reduce aggregation of AAV particles in the composition using methods, such as addition of surfactants, pH adjustment, salt concentration adjustment (page 21, lines 29-32).
However, Gao et al. fails to specifically teach that the pH of the pharmaceutical composition is 7.3 and the concentration of the PF68 surfactant used is 0.001%.
However, it would have been prima facie obvious to one of the ordinary skills in the art before the effective
filing date of the claimed invention to have specified the pH of the pharmaceutical composition to be 7.3 and the concentration of PF68 surfactant used to 0.001% with a reasonable expectation of success. One would have been motivated to have optimized the pH of the pharmaceutical composition and the concentration of the surfactant in the method taught by Gao et al. to reduce aggregation of AAV particles in the composition.
Regarding claim 39: Following discussion of claim 38 above, Gao et al. further teaches that the pharmaceutical composition is administered to the subject in a therapeutically effective amount by intravenous administration (page 2, lines 15-16).
Claim(s) 1, 11, 25, 28, 30, 33, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Scaria et al. (US20170096683A1, filed on 05/02/2015, and published on 04/06/2017), as evidenced by Dabaj et al. (Dabaj et al., “NGLY1 Deficiency: A Rare Newly Described Condition with a Typical Presentation”. Life (Basel). 2021 Feb 27;11(3):187).
Regarding claim 1, the teachings of Gao et al. and Scaria et al. are set forth in detail above.
Regarding claims 11, 25, and 35: Following discussion of claim 1 above, although Gao et al. fails to specifically teach that the level of GNA in the plasma, urine or other tissue sample is reduced between 10% and 90% at least 5 weeks, 10 weeks, 20 weeks or 30 weeks after administration of the nucleic acid construct compared to its level before administration, Dabaj et al. provides evidence that accumulation of GlcNAc1-Asn (GNA) is due to NGLYI deficiency by specifically teaching that NGLY1 deficiency was confirmed upon the identification of an abnormal urine oligosaccharide (Neu5Ac1Hex1GlcNAc1-Asn) (GNA) (page 6, paragraph 2, lines 11-13). Since the steps of
the claimed method of treating NGLY1 deficiency and the method steps taught by Gao et al. are the
same, the claimed reduction in GNA levels in the urine sample after administration of the nucleic acid construct encoding NGLY1 is inherently and necessarily present in Gao et al. Accordingly, the mere recitation of its presence in the instant claims is not sufficient to distinguish the instant claims from prior art. When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004). See MPEP 2112.02.
Regarding claim 28: Following discussion of claim 25 above, Gao et al. further teaches that the nucleic acid encoding a NGLY 1 protein is generally operably linked to a promoter, wherein the promoter is a constitutive promoter, for example a chicken beta-actin (CAG) promoter (page 7, lines 17-20).
Regarding claim 30: Following discussion of claim 25 above, Gao et al. further teaches that the nucleic acid sequence further comprises a woodchuck hepatitis vims posttranscriptional regulatory element (WPRE) (page 10, lines 7-10) and a rabbit beta- globulin poly A signal sequence (page 10, lines 4-5).
Regarding claim 33: Following discussion of claim 25 above, Gao et al. further teaches that the nucleic acid comprises the sequence as set forth in SEQ ID NO: 1, which is 100% identical to instant SEQ ID NO: 9 at positions 1123-1182 (please see below a screenshot of the Query match).
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Claim(s) 25 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Scaria et al. (US20170096683A1, filed on 05/02/2015, and published on 04/06/2017), as evidenced by Dabaj et al. (Dabaj et al., “NGLY1 Deficiency: A Rare Newly Described Condition with a Typical Presentation”. Life (Basel). 2021 Feb 27;11(3):187), as applied to claim 25 above and further in view of Alberts, et al. (Alberts, et al., "Molecular Biology of the Cell, Fifth Edition". New York:Garland Science, 2008. Pages 1-3 and 367).
Regarding claim 25, the teachings of Gao et al., Scaria et al., and Dabaj et al. are set forth in detail above.
Regarding claim 27: Following discussion of claim 25 above, Gao et al. teaches SEQ ID NO: 1, which is 99.8% similar to instant SEQ ID NO: 1 (please see above under the discussion of claim 3, a screenshot of the Query match, wherein the sequences only differ at the nucleotide at position 93 (A vs. C)).
However, Gao et al. in view of Scaria et al. and Dabaj et al. fails to teach that the NGLY1 coding sequence is 100% identical to SEQ ID NO: 1.
However, Alberts, et al. teaches that both GCA and GCC codons encode for the same amino acid (Ala) (page 367, Figure 6-50).
Based on the teachings of Gao et al. of a similar nucleotide sequence encoding the NGLY1 coding sequence and the teachings of Alberts et al. that both GCA and GCC codons encode for the same amino acid (Ala), 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 have used the nucleotide sequence of the nucleic acid of SEQ ID NO: 1 taught by Gao et al. and modified it to substitute the (C) nucleotide at position 93 of SEQ ID NO: 1 for (A) nucleotide as this modification represents nothing more than the substitution of one codon of the nucleotide sequence for another that encodes for the same amino acid with predictable results.
Claim(s) 25 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (WO2020210592A1, filed on 04/10/2020, and published on 10/15/2020), in view of Scaria et al. (US20170096683A1, filed on 05/02/2015, and published on 04/06/2017), as evidenced by Dabaj et al. (Dabaj et al., “NGLY1 Deficiency: A Rare Newly Described Condition with a Typical Presentation”. Life (Basel). 2021 Feb 27;11(3):187), as applied to claim 25 above and further in view of Nolte et al. (US20210139563A1, filed on 05/02/2019, and published on 05/13/2021).
Regarding claim 25, the teachings of Gao et al., Scaria et al., and Dabaj et al. are set forth in detail above.
Regarding claim 34: Following discussion of claim 25 above, Gao et al. further teaches that the rAAV is an AAV9 capsid (claim 14 of Gao et al.).
However, Gao et al. in view of Scaria et al. and Dabaj et al. fail to teach that the rAAV has a capsid that is at least 95% identical to SEQ ID NO: 10 (AAV9 sequence).
However, Nolte et al. teaches an AAV9 serotype sequence of SEQ ID NO: 59, which is 100% identical to instant SEQ ID NO: 10 (please see above under the discussion of claim 10 a screenshot of the Query match).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have substituted the amino acid sequence of Gao et al. with the AAV9 serotype sequence of SEQ ID NO: 59 of Nolte et al. as this substitution represents nothing more than the substitution of one amino acid sequence with another with predictable results.
Allowable Subject Matter
Claims 7 and 31 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 7 and 31 are considered free of prior art for the following reasons:
The closest prior art of record Gao et al. teaches a method of treating a subject having NGLYl deficiency (page 1, lines 22-23). The method involves administering to the subject an effective amount of an rAAV comprising a capsid containing a nucleic acid engineered to express NGLYl, e.g., in the central nervous system (CNS) of a subject (page 1, lines 24-26). The rAAV comprises an artificial transcription element that is operably linked to a transgene encoding NGLYl (page 18, lines 10-14). Gao et al. further teaches that the administration is by intrathecal injection (claim 13 of Gao et al.). However, Gao et al. fails to teach administering to the subject the effective amount of an rAAV comprising the nucleic acid construct comprising a transgene encoding NGLY1 by ICV administration or via the cisterna magna. Gao et al. also fails to teach that the nucleic acid construct comprises the nucleotide sequence of SEQ ID NO: 8.
Overall, the prior art fails to sufficiently teach or render obvious a nucleic acid construct comprising a transgene encoding NGLY1 operably linked to regulatory elements for expression in the CNS of a subject that comprises the nucleotide sequence of SEQ ID NO: 8 as claimed.
The instant claimed nucleic acid construct that comprises a transgene encoding NGLY1 for expression in the CNS of a subject is considered allowable in view of the prior art of record, such that a person having ordinary skills in the art, at the time invention was made, would not have envisaged the nucleic acid molecule construct of SEQ ID NO: 8 as currently claimed, nor does the prior art render obvious the product currently claimed.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue
fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly
labeled “Comments on Statement of Rea sons for Allowance.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633