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 .
Claims 72-91, of record 12/27/2024, are pending and subject to prosecution.
Priority
The instant application is a CON of application 17/044232 (US patent 12121563, filed 9/30/2020), which is a national stage entry of PCT/US2019/026638 (filed 4/9/2019), which claims benefit of provisional applications 62/655043 (filed 4/9/2018), 62/742835 (filed 10/8/2018), and 62/810281 (filed 2/25/2019).
Specification
The use of the term Lasergene, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 80 and 88 are objected to because of the following informalities:
In claims 80 and 88, the limitation “PHP.Eb” should be replaced with “PHP.eB”.
Appropriate correction is required.
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.
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Claims 72-91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12121563. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 72: Patented claim 1 recites expression construct comprising (i) an enhancer having the sequence as set forth in SEQ ID NO: 3 (which encodes an hl56i-derived enhancer and therefore reads on “selective expression… in inhibitory neurons”); (ii) a promoter having the sequence as set forth in SEQ ID NO: 30 or SEQ ID NO: 31; and (iii) a coding sequence encoding a protein that rescues voltage-gated sodium channel function. The patented claim anticipates the instant claim.
Regarding claim 73: Following the discussion of claim 72, patented claim 2 recites the expression construct of patented claim 1, wherein the coding sequence comprises a sequence as set forth in SEQ ID NO: 10, SEQ ID NO: 10 with a D60N mutation, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 24. The patented claim anticipates the instant claim.
Regarding claim 74: Following the discussion of claim 72, patented claim 3 recites an expression construct comprising (i) an enhancer having 3, 4, 5, 6, 7, 8, or 9 copies of the sequence consisting of the sequence as set forth in SEQ ID NO: 2; (ii) a promoter; and (iii) a coding sequence encoding a protein that rescues voltage-gated sodium channel function. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 75: Following the discussion of claims 72 and 74, patented claim 4 recites the expression construct of patented claim 3, wherein the coding sequence comprises a sequence as set forth in SEQ ID NO: 10, SEQ ID NO: 10 with a D60N mutation, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 24. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 76: Following the discussion of claims 72 and 74, patented claim 5 recites the expression construct of patented claim 3, wherein the expression construct further comprises a coding sequence for a reporter protein and a skipping element. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 77: Following the discussion of claims 72 and 74, patented claim 6 recites the expression construct of patented claim 3, wherein the expression construct is within an adeno-associated viral (AAV) vector. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 78: Following the discussion of claims 72 and 74, patented claim 7 recites the expression construct of patented claim 3, wherein the expression construct has the sequence as set forth in SEQ ID NO: 39, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 34, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 49, or SEQ ID NO: 51. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 79: Following the discussion of claims 72 and 74, patented claim 8 recites the expression construct of patented claim 3, wherein the expression construct is associated with a capsid that crosses the blood brain barrier. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 80: Following the discussion of claims 72, 74, and 79, patented claim 9 recites the expression construct of patented claim 8, wherein the capsid comprises PHP.Eb. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 81: Following the discussion of claims 72, 74, and 79, patented claim 10 recites the expression construct of patented claim 8, wherein the capsid comprises the sequence as set forth in SEQ ID NO: 53. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 82: Following the discussion of claims 72, 74, and 79, patented claim 11 recites the expression construct of patented claim 8, wherein the capsid comprises an AAV9 capsid with an insert having the sequence as set forth in SEQ ID NO: 54 or SEQ ID NO: 55. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 83: Following the discussion of claims 72, 74, and 79, patented claim 12 recites the expression construct of patented claim 8, wherein the capsid comprises an AAV2 capsid with an insert having the sequence as set forth in SEQ ID NO: 56. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 84: Following the discussion of claim 72, patented claim 13 recites a method for treating Dravet Syndrome in a subject in need thereof wherein the method comprises administering a therapeutically effective amount of an expression construct comprising: (i) an enhancer having the sequence as set forth in SEQ ID NO: 3; (ii) a promoter; and (iii) a coding sequence that encodes a protein that rescues voltage-gated sodium channel function, thereby treating Dravet Syndrome in the subject in need thereof. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 85: Following the discussion of claims 72 and 84, patented claim 14 recites the method of patented claim 13, wherein the promoter has the sequence as set forth in SEQ ID NO: 30 or SEQ ID NO: 31. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 86: Following the discussion of claims 72 and 84, patented claim 15 recites the method of patented claim 13, wherein the coding sequence has the sequence as set forth in SEQ ID NO: 10, SEQ ID NO: 10 with a D60N mutation, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, or SEQ ID NO: 24. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 87: Following the discussion of claims 72 and 84, patented claim 16 recites the method of patented claim 13, wherein the administering is intravenous and the expression construct is associated with a capsid that crosses the blood brain barrier. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 88: Following the discussion of claims 72, 84, and 87, patented claim 17 recites the method of patented claim 16, wherein the capsid comprises PHP.Eb. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 89: Following the discussion of claims 72, 84, and 87, patented claim 18 recites the method of patented claim 16, wherein the capsid comprises the sequence as set forth in SEQ ID NO: 53. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 90: Following the discussion of claims 72, 84, and 87, patented claim 19 recites the method of patented claim 16, wherein the capsid comprises an AAV9 capsid with an insert having the sequence as set forth in SEQ ID NO: 54 or SEQ ID NO: 55. The combined limitations of the patented claims render obvious the instant claim.
Regarding claim 91: Following the discussion of claims 72, 84, and 87, patented claim 20 recites the method of patented claim 16, wherein the capsid comprises an AAV2 capsid with an insert having the sequence as set forth in SEQ ID NO: 56. The combined limitations of the patented claims render obvious the instant claim.
Claims 72, 74, and 79-80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 73-75, 81, and 83-84 of co-pending Application No. 18263930 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 72: Co-pending claim 73 recites an artificial expression construct comprising (i) a first enhancer having the sequence of SEQ ID NO: 4 or SEQ ID NO: 5; (ii) a second enhancer having the sequence of SEQ ID NO: 14, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 84, or SEQ ID NO: 85; (iii) a promoter; and (iv) a coding sequence. Co-pending claim 75 recites the artificial expression construct of claim 73, wherein the first enhancer has a sequence as set of SEQ ID NO: 6 (which is identical to the sequence of instant SEQ ID NO 3, see alignment below (first 120 nt displayed)) or SEQ ID NO: 7.
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Co-pending claim 81 recites the artificial expression construct of claim 73, wherein the coding sequence is a codon-optimized SLC6A1 gene (which reads on “a coding sequence encoding a protein that rescues voltage-gated sodium channel function”) having the sequence of SEQ ID NOs: 22, 25, 28, 31, 34, or 38-45. The combined limitations of the co-pending claims render obvious the instant claim.
Regarding claim 74: Following the discussion of claim 72, co-pending claim 74 recites the artificial expression construct of claim 73, wherein the first enhancer has 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 copies of the sequence of SEQ ID NO: 4 (which is identical to the sequence of instant SEQ ID NO 2, see alignment below (first 120 nt displayed)) or SEQ ID NO: 5.
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The combined limitations of the co-pending claims render obvious the instant claim.
Regarding claims 79-80: Following the discussion of claim 72, co-pending claim 83 recites the artificial expression construct of claim 73, wherein the artificial expression construct is associated with a capsid that crosses the blood brain barrier. Co-pending claim 84 recites the artificial expression construct of claim 83, wherein the capsid comprises PHP.eB, AAV-BR1, AAV-PHP.S, AAV-PHP.B, AAV-PPS, AAV9, AAVrh.10, AAV1R6, or AAV1R7. The combined limitations of the co-pending claims render obvious the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 72, 77, and 79 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116, 123-124, and 128-130 of co-pending Application No. 19153092 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 72: Co-pending claim 116 recites a system to express a functional SCN1A protein (which reads on “a coding sequence encoding a protein that rescues voltage-gated sodium channel function”) in a subject in need thereof comprising: (i) a first artificial expression construct comprising a first portion of an SCN1A coding sequence, an N-intein coding sequence, and a first promoter sequence, wherein the N-intein coding sequence is located at the 3' end of the first portion of the SCN1A coding sequence; and (ii) a second artificial expression construct comprising a second portion of the SCN1A coding sequence, a C-intein coding sequence, and a second promoter sequence, wherein the C-intein coding sequence is located at the 5' end of the second portion of the SCN1A coding sequence; wherein when the first artificial expression construct and the second artificial expression construct are expressed in a central nervous system cell type, a protein product of the first portion of the SCN1A coding sequence and a protein product of the second portion of the SCN1A coding sequence are linked to form the functional SCN1A protein. Co-pending claim 123 recites the system of co-pending claim 116, wherein the first artificial expression construct further comprises a first enhancer sequence that leads to targeted expression of the first portion of the SCN1A coding sequence within a targeted central nervous system cell type and the second artificial expression construct further comprises a second enhancer sequence that leads to targeted expression of the second portion of the SCN1A coding sequence within the targeted central nervous system cell type. Co-pending claim 124 recites the system of co-pending claim 123, wherein the first enhancer sequence comprises the sequence of SEQ ID NO: 2 (which is identical to the sequence of instant SEQ ID NO 2, see alignment below (first 120 nt displayed)) or a sequence having at least 95% sequence identity to the sequence of SEQ ID NO: 2, the second enhancer sequence comprises the sequence of SEQ ID NO: 2 or a sequence having at least 95% sequence identity to the sequence of SEQ ID NO: 2, and the targeted central nervous system cell type is a forebrain GABAergic neuron.
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The co-pending claims recite a two-vector split gene expression system for SCN1A comprising an enhancer at least 95% identical to instant SEQ ID NO 3 and promoters, which renders obvious the expression construct of the instant claim.
Regarding claim 77: Following the discussion of claim 72, co-pending claim 128 recites a vector system comprising: (i) a first artificial expression construct comprising a first portion of an SCN1A coding sequence, an N-intein coding sequence, and a first promoter sequence, wherein the N-intein coding sequence is located at the 3' end of the first portion of the SCN1A coding sequence; and (ii) a second artificial expression construct comprising a second portion of the SCN1A coding sequence, a C-intein coding sequence, and a second promoter sequence, wherein the C-intein coding sequence is located at the 5' end of the second portion of the SCN1A coding sequence; wherein when the first artificial expression construct and the second artificial expression construct are expressed in a central nervous system cell type, a protein product of the first portion of the SCN1A coding sequence and a protein product of the second portion of the SCN1A coding sequence are linked to form a functional SCN1A protein; wherein the first artificial expression construct is within a first vector and the second artificial expression construct is within a second vector. Co-pending claim 129 recites the vector system of co-pending claim 128, wherein the first vector is a first recombinant adeno-associated viral (AAV) vector and the second vector is a second recombinant AAV vector. The combined limitations of the co-pending claims render obvious the instant claim.
Regarding claim 79: Following the discussion of claims 72 and 77, co-pending claim 130 recites the vector system of co-pending claim 128, wherein the first artificial expression construct is associated with a capsid that cross the blood brain barrier and the second artificial expression construct is associated with a capsid that cross the blood brain barrier. The combined limitations of the co-pending claims render obvious the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 72, 79-80, and 84 are are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 18-19, 22, 26, and 28-29 of co-pending Application No. 19510109 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claim 72: Co-pending claim 1 recites a system to express one or more coding sequences (which inherently reads on “comprising… a promoter”), the system comprising: (i) a first expression construct comprising: a first portion of a polynucleotide sequence of a gene encoding the sodium channel alpha subunit, and a polynucleotide sequence encoding an N-fragment of a split intein (N- intein), at the 3' end relative to the first portion of the polynucleotide sequence of the gene encoding the sodium channel alpha subunit; (ii) a second expression construct comprising: a second portion of the polynucleotide sequence of the gene encoding the sodium channel alpha subunit, and a polynucleotide sequence encoding a C-fragment of the split intein (C- intein), at the 5' end relative to the second portion of the polynucleotide sequence of the gene encoding the sodium channel alpha subunit; and (iii) optionally, a third expression construct comprising a polynucleotide sequence encoding a degron; wherein if the third expression construct is not included in the system, the first expression construct, the second expression construct, or both further comprises a polynucleotide sequence encoding a degron, located if within the first expression construct at the 3' end relative to the first portion of the polynucleotide sequence of the gene encoding the sodium channel alpha subunit, or located if within the second expression construct at the 5' end relative to the second portion of the polynucleotide sequence of the gene encoding the sodium channel alpha subunit. Co-pending claim 3 recites the system of co-pending claim 1, wherein the first and/or the second expression construct further comprises an enhancer sequence and a promoter sequence, and optionally an intron having a polynucleotide sequence of SEQ ID NO:107. Co-pending claim 18 recites the system of co-pending claim 3, wherein the enhancer sequence is configured for targeted expression of the first, the second, or both portions, respectively, of the polynucleotide sequence of the gene encoding the sodium channel alpha subunit within a targeted central nervous system cell type; preferably the targeted central nervous system cell type being GABAergic (which reads on “inhibitory neurons”), glutamatergic, or both cell types. Co-pending claim 19 recites the system of co-pending claim 3, wherein the enhancer sequence is set forth in SEQ ID NO: 2 (DLX2.0) (which is identical to instant SEQ ID NO 3, see alignment below (first 120 nt displayed)) or has a concatemerized core having a polynucleotide sequence of SEQ ID NO:1, or the targeted central nervous system cell type comprises a GABAergic interneuron; or wherein the enhancer sequence is set forth in SEQ ID NO: 55 (eHGT_078h), or the targeted central nervous system cell type comprises a glutamatergic neuron.
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The split-gene multi-construct system for expressing a sodium channel subunit of the co-pending claims renders obvious the expression construct of the instant claim.
Regarding claims 79-80: Following the discussion of claim 72, co-pending claim 22 recites the artificial expression construct, comprising the first, the second or the third expression construct of the system of co-pending claim 1, wherein the artificial expression construct is associated with a capsid that crosses the blood brain barrier, wherein the capsid comprises PHP.eB. AAV-BR1, AAV-PHP.S, AAV-PHP.B, or AAV-PPS. The combined limitations of the co-pending claims render obvious the instant claims.
Regarding claim 84: Following the discussion of claim 72, co-pending claim 26 recites a method of rescuing voltage-gated sodium channel function within a targeted population of cells, the method comprising: administering a therapeutically effective amount of the system of co-pending claim 1 to a sample or subject comprising the targeted population of cells, and inducing expression of the first expression construct and the second expression construct of the system to reconstitute a sodium channel alpha subunit, thereby rescuing voltage-gated sodium channel function within the targeted population of cells, wherein the subject has a sodium channelopathies, optionally comprising Dravet syndrome, myoclonic seizures, myoclonic astatic epilepsy (MAE), intractable childhood epilepsy with generalized tonic-clonic seizures, simple febrile seizures, generalized epilepsy and febrile seizures plus (GEFS+), migrating partial seizures of infancy, Lennox-Gastaut syndrome, or West syndrome. Co-pending claim 28 recites the method of claim co-pending 26, wherein the subject is a pediatric patient having Dravet syndrome. Co-pending claim 29 recites a method of administering a system of expression constructs to a subject in need thereof, comprising administering a therapeutically effective amount of the system of co-pending claim 1 to a sample or subject comprising the targeted population of cells, and inducing expression of the first expression construct and the second expression construct of the system to reconstitute a sodium channel alpha subunit, thereby rescuing voltage-gated sodium channel function within the targeted population of cells, wherein the subject in need thereof has a sodium channelopathies, optionally comprising Dravet syndrome, myoclonic seizures, myoclonic astatic epilepsy (MAE), intractable childhood epilepsy with generalized tonic-clonic seizures, simple febrile seizures, generalized epilepsy and febrile seizures plus (GEFS+), migrating partial seizures of infancy, Lennox-Gastaut syndrome, or West syndrome. The combined limitations of the co-pending claims render obvious the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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