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 .
Priority
Current application is a national stage 371 application of PCT/US2021/061346. The PCT claims priority to US provisional applications 63/179,807 and 63/119,860, with their filing date 4/26/2021 and 12/01/2020.
Application Status
Claims 1-15 and 18-22 are currently pending.
Drawings
The drawings are objected to because Figures 1 (A-C), 2 (A-C), 5, 6, and 8 are objected to as the figure title is not oriented correctly with regards to the figure itself. Figure titles must be oriented in the same direction as the view so as to avoid having to rotate the sheet. Reference characters should be arranged to follow the profile of the object depicted." See MPEP 608.02.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-15 and 18-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating gait, nest building ability, and motor coordination in an Angelman syndrome subject by administering to the subject a composition comprising an AAV vector expressing an UBE3A nucleic acid sequence, it does not reasonably provide enablement for the broad array of symptoms associated with Angelman syndrome in a subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States vs Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant Wands factors are indicated below:
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
The nature of the invention;
The breadth of the claims;
The state of the prior art;
The level of skill in the art;
The level of predictability in the art;
The amount of direction provided by the inventor;
The presence or absence of working examples;
The quantity of experimentation necessarily needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
Further MPEP §2164.01(c) recites, “When a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation. See In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991) (claiming a chimeric gene capable of being expressed in any cyanobacterium and thus defining the claimed gene by its use).”
Claim 1 recites a composition of rAAV and intended use for the treatment of Angelman syndrome. Since claim 1 recites the limitation ‘useful for treatment of Angelman syndrome’ the claim is analyzed for enablement requirements of treatment using the recited composition. Claims 2-15 and 18-22 are included because they depend on claim 1.
Claims 18-21 recite a method for treating one or more symptoms of Angelman syndrome by administering the composition of claim 1 to a patient in need thereof, where the composition is delivered intrathecally to the patient. Based on the specification, the patient or subject are defined as a male or female mammalian animal, including a human, a veterinary or farm animal, a domestic animal or pet, and animals normally used for clinical research (see line 8, page 12). In one embodiment, the subject of these methods and compositions is a male or female human. The symptoms for treatment include delayed development, intellectual disability, severe speech impairment, ataxia, and/or epilepsy.
Regarding these claims, at the time of the instant application, journal articles, including one from Nenninger et al. (2021), discusses the state of the art by showing a method for improving gene therapy for Angelman syndrome with secreted human UBE3A. Nenninger describes experimental procedure with rAAV to introduce a functional copy of UBE3A. Previous experiments from the group showed a rAAV expressing mouse Ube3a could rescue deficits in a mouse model of AS (see abstract). Here, the group expanded on the work and approach with a second AS model using secreted human UBE3A gene known as STUB (see results). The model was a rat with a full deletion of the rat Ube3a gene (see introduction) and when introduced with an rAAV expressing STUB, showed improved behavioral deficits (see Fig. 6). Furthermore, the results provided in the specification of the instant application (Fig 9A-B, 10A-D, and 11A-D) shows mice injected with a rAAV expressing engineered UBE3A1 isoform protein exhibited differential changes in motor coordination, nest building ability, and straight length and gait improvement.
However, it is important to note that neither the specification of the instant application, or the article by Nenninger et al., describes the extent of which rAAV gene therapy treatment is readily applicable to human subjects as included in the claim set. In both cases, the models used were both rodents, and Nenninger concluded that these results introduce new consideration when designing a gene therapy treatment for human AS and shed much-needed light on the yet unknown UBE3A mechanism of action underlying the severe effects of UBE3A deficiency.
Nature of the Invention
The claimed invention directs to a composition and method of use for said composition to treat Angelman syndrome in a patient. A patient in this case being a male or female mammalian animal, including a human, a veterinary or farm animal, a domestic animal or pet, and animals normally used for clinical research (see page 12 of the specification). The composition comprises of a recombinant adeno-associated virus (rAAV) further comprising of an AAV capsid and a vector genome package where the vector genome has a UBE3A nucleic acid sequence encoding the UBE3A isoform 1 protein. This composition is delivered intrathecally to the patient.
Thus, the claimed invention requires reliable implementation of the composition to the patient and evaluating the efficacy of the composition on the subject that has a mutation in the UBE3A gene.
The Breadth of the Claims
The scope of claim 1 and dependent claims 18-21 states that the delivery of the composition results in treatment of one or more symptoms that can include delayed development, intellectual disability, severe speech impairment, ataxia and/or epilepsy. This administration must further be deemed useful, which can be interpreted as showing a significant improvement in said symptoms. Furthermore, the patient comprises a wide range of organisms including humans, farm animals, animals used for clinical research, or domestic pets.
Guidance of the Specification
The specification recites treatment administered to a subject as defined as mice with the therapeutic goal of increasing UBE3A Isoform 1 expression to any amount of the normal or non-AS level, or as compared to levels of UBE3A expression before treatment (see page 39). Administration of AAB-PHP was done at a dose of 1 x 1010 GC/animal. The resulting treatment of UBE3A Isoform 1 in mice showed a statistically significant improvement in gait, nest building ability, and motor coordination (See page 45, Figures 9A and 9B, 10 A and 10B, and 11A-11D). While mice is a recognized model for studying Angelman syndrome, the specification does not provide any guidance or evidence as to how the results in the mouse model disclosed is cam be applicable to a human model to treat intellectual disability, ataxia, epilepsy, or severe speech impairment.
The State of the Prior Art
The prior art showed that treating AS in human subjects is not enabled by administering a nucleic acid molecule encoding UBE3A or a vector comprising the nucleic acid sequence for UBE3A as prior art only shows administration to mice or rats and at the time of the instant application (see abstract of Nenninger et al.). Furthermore, there are no gene therapy treatments for Angelman syndrome shown to be effective or useful in humans. Another study, done by Hinderer et al. (2018), showed that high-dose intravenous administration of AAVhu68 (a variant claimed in the instant application for its ability to access neurons) resulted in severe toxicity in nonhuman primates (see results section). Therefore, one cannot assume that the effectiveness of gene therapy using rAAV in rodents would be applicable given the significantly larger volume of the human brain alongside restrictions on the amount of vector that can be introduced to human patients (see discussion of Nenninger et al.).
The Quantity of Undue Experimentation
In light of the limited amount of research into approved treatments for AS in humans as a subject, the quantity of experimentation necessarily needed to make or use the invention as claimed with regards to claims 1-15 and 18-22 for use of treatment in a patient, which includes a human, is considerably high, especially with regards to treating symptoms such as delayed development, intellectual disability, severe speech impediment, and ataxia.
One skilled in the art would have to conduct extensive experiments which includes administering the claimed composition into human individuals, record a measurable amount of significant improvement in the symptoms listed, and ensure safety from toxicity of large-dose AAV administration.
Conclusion of 35 U.S.C. 112(a) Enablement Analysis
After applying the Wands factors and analysis to claims 1-22, taking into consideration the factors outlined above, it is concluded that the specification is not fully enabled as discussed above. There is no evidence that the composition and use of said composition presented above have been administered to all “patients” or “subjects” as claimed, therefore, claims 1-15 and 18-22 are rejected under 35 U.S.C. 112(a) for failing to disclose sufficient information to enable a person of skill in the art to use the invention commensurate in scope with these claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 5, 6, 15, 18, 21, and 22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WIPO publication WO/2020/191366 (Published 09/24/2020, based on application number 17/439,140 filed on 03/20/2020, which claims priority to provisional application 62/821,442, filed on 03/21/2019), herein referred to as Arulanandam et al.
Regarding claim 1, Arulanandam teaches a rAAV (see paragraph 0005) UBE3A vector comprising a nucleic acid and protein component, where the nucleic acid comprises of a 5’ inverted terminal repeat (ITR) sequence, a promoter or regulatory element downstream of the 5’ ITR, a UBE3A nucleotide sequence which can be either SEQ ID NO: 25, which has a 100% identity to SEQ ID NO: 2 of the instant application, and a 3’ ITR downstream of the UBE3A nucleotide sequence (See paragraphs 0007-0010, and 0021).
Regarding claim 2, Arulanandam teaches that in some cases, tissue-specific regulatory sequences bind tissue-specific transcription factors that induce transcription in a tissue specific manner/ Such tissue-specific regulatory sequences (e.g., promoters, enhancers, etc.) are well known in the art. Exemplary tissue-specific regulator sequences include, but are not limited to the following tissue specific promoters: neuronal such as neuron-specific enolase (NSE) promoter, neurofilament light-chain gene promoter, etc. (see paragraph 0144).
Regarding claim 5, Arulanandam teaches that in addition to the major elements identified above for the recombinant AAV vector, the vector also includes conventional control elements which are operably linked to the transgene in a manner which permits its transcription, translation, and/or expression in a cell transfected with the plasmid vector produced by the disclosure. Furthermore, a great number of expression control sequences, including promoters which are native, constitutive, inducible and/or tissue-specific, are known in the art and may be utilized (see paragraph 0132).
Regarding claim 6, Arulanandam teaches that the term “transcription regulatory sequence” feres to a DNA sequence that controls and regulates transcription and/or translation of another DNA sequence. These sequences include, but are not limited to, promoters, enhancers, polyadenylation signals and silencers (see paragraph 0102). Furthermore, Arulanandam discloses that for nucleic acid encoding proteins, a polyadenylation sequence generally is inserted following the transgene sequences. A rAAV construct useful in the present disclosure may also contain an intron (see paragraph 0133).
Regarding claim 15, Arulanandam teaches that the AAV vector produced in a prior example was suspended in 0.1M phosphate buffered saline (PBS) (see paragraph 0214).
Regarding claims 18, 19, 20, 21, and 22, Arulanandam teaches a “subject” is a mammal (e.g., a non-human mammal), more preferably a primate and still more preferably a human. Mammals include, but are not limited to, primates humans, farm animals, rodents, sport animals, and pets (see paragraph 0095), and the administration of AAV to said subject which reads on a “patient” in the instant application (claim 18).
Furthermore, Arulanandam teaches that the term “normal” or “control” refers to sample or cells or patient which are assessed as not having Angelman syndrome, or any other UBE3A deficient neurological disorder (see paragraph 0129). In some cases, an AAV is administered to UBE3A deficient-mice (see paragraph 0234-0236), therefore reading on administering a composition to a patient in need thereof treatment due to having a UBE3A deficiency (claim 19).
Furthermore, Arulanandam teaches that “treatment” or “treating” a subject includes amelioration and/or elimination of one or more symptoms associated with Angelman Syndrome, which symptoms comprises of learning and memory deficits (see paragraph 0090, 0120, and 0121). In some cases, administration of a vector can be intravenously, intrathecally, intracranially, etc. (see paragraph 0180). This reads on part of the scope of claim 20 and claim 21.
Finally, with regards to claim 22, Arulanandam teaches a vector is administered to a subject from a range at a titer of at least 1x109 to 100x1012 GC/mL (see paragraph 0184). In Arulanandam, genome copies are presented in GC/mL where in the instant application, genome copies are presented as GC/kg. To do a conversion, the density of the sample must be noted. However, if one was to base the conversion off the sample density of water (1.00 kg/L), then 1x1010 GC/kg is equivalent to about 1x1013 GC/mL. Within the range presented in Arulanandam, the range of the instant application is anticipated.
Absent evidence to the contrary, the composition described in Arulanandam has the same composition of a rAAV in the instantly claimed application as well as methods of administration. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See MPEP 211.2 and 2112.
Thus, Arulanandam clearly anticipate instant claims 1, 2, 5, 6, 15, 18, 21, and 22.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Arulanandam (Arulanandam et al., US 20220152223 A1, published 05/19/2022, claiming priority to US provisional application 62/821,442, filed on 05/21/2019) in view of Li et al. (WO 2021/081201 A1, published 04/29/2021 with an international filing date of 10/22/2020, claiming priority to US application 62/924,340 filed on 10/22/2019).
Regarding claims 3 and 4, Arulanandam teaches a composition comprising a stock of recombinant adeno-associated virus (rAAV) that is useful for treating Angelman syndrome (AS) as described above. Arulanandam teaches that the regulatory promoter of claim 1 comprises of a neuron-specific promoter.
Arulanandam does not teach that the neuron-specific promoter is a synapsin promoter. Furthermore, Arulanandam does not teach where the synapsin promoter is a shortened promoter having the nucleic acid sequence of SEQ ID NO: 12 (claim 4).
Li teaches an adeno-associated virus (AAV) systems for the treatment of progranulin associated neurodegenerative diseases or disorders. Li teaches that, in some embodiments, the promoter is a human synapsin-1 gene (hSyn1) promoter. Fig. 3 shows the nucleic acid sequence of the human synapsin-1 gene promoter (SEQ ID NO: 2). SEQ ID NO: 2 of Li and SEQ ID NO: 12 of the instant application has 100% identity.
It would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have adapted the rAAV composition of Arulanandam with the synapsin promoter of Li for the expression of UBE3A in the instant application for the treatment of Angelman syndrome as Angelman syndrome is a neurological disorder which is encompassed by the nervous system. It would have been obvious to use the synapsin promoter presented by Li, in order to limit the expression of transgenes to neuronal tissues, thereby minimizing the risk of off-target effects when treating Angelman syndrome.
In view of the foregoing, claims 3 and 4, taken as a whole, would have been prima facie obvious before the effective filing date.
Claims 7-12,21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Arulanandam et al., in view of Hordeaux (Hordeaux et al., WO 2020/132455 A1, published 05/25/2020, with priority to US application 62/783,956, 12/21/2018) as disclosed in the Information Data Sheet.
Regarding claim 7, 8, and 9, Arulanandam teaches the rAAV composition for the treatment of Angelman syndrome, as mentioned above.
Arulanandam does not teach where the rAAV composition comprises of regulatory sequences that comprise of one or more targeting sequence for miR in dorsal root ganglia selected from miR182 and/or miR183, wherein these said regulatory sequences further comprise of four targeting sequences and where the targeting sequences are located downstream of the UBE3A nucleic acid sequence. Furthermore, Arulanandam does not teach where the regulatory sequences comprise of four copies of SEQ ID NO: 11.
Regarding claims 7 and 8, Hordeaux teaches, in certain embodiments, an expression cassette or vector genome containing a transgene that is operably linked to one or more miRNA target sequences provided herein. In some embodiments, the vector genome is designed to contain multiple miRNA target sequence (see page 15, lines 5-10). Furthermore, the miRNA target sequences are incorporated into the UTR of the transgene (i.e. 3’ or downstream of the gene open reading frame) (see page 15, line 11 of the specification).
Regarding claim 9, Hordeaux describes the composition of the expression cassette comprises of four miRNA target sequences located in the 3’ UTR (See pg. 80, line 1 of the specification, and claim 10).
Regarding claim 10, Hordeaux teaches a targeting sequence of miR183, described as SEQ ID NO: 1. SEQ ID NO: 11 of the instant application has 100% identity to SEQ ID NO: 1 of Hordeaux.
Regarding claim 11 and 12, Hordeaux describes novel AAVhu68 capsids (nucleic acid SEQ ID NO: 8) which has 100% identity to SEQ ID NO: 14 of the instant application claim 12. AAVhu68 is a variant of AAV9 with two amino acid modifications. AAV9 is a well-known AAV to have demonstrated the ability to transduce spinal alpha motor neurons when administered intravenously at high doses. AAVhu68 has been shown to have toxicity in non-human primates (NHP) (as evident in Hinderer et al.)
Regarding claim 21 and 22, Hordeaux administered the composition intrathecally to the patient (see pg. 60, line 9 of the specification) at a dosage of 1X1012 GC/kg (see page 62, line 7 of the specification).
It would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have adapted the rAAV composition of Arulanandam with the targeting sequences for miR183 and method of administration as described in Hordeaux. Though untoward responses of host to AAV vectors have been minimal, the expansion of clinical applications of AAV gene therapy has shown toxicities to subjects that can limit the clinical impact of this technology (Hordeaux) (see background, pg. 1, line 23 of the specification). The most severe toxicities have occurred following intravenous administration of high doses of AAV to target the CNS and musculoskeletal system.
Hordeaux teaches a composition and method for AAV delivery which specifically represses transgene expression in DRG neurons. Advantageously, these compositions decrease neuronal degradation and/or decrease secondary dorsal spinal cord axonal degeneration which can be caused by overexpression and/or immune-mediate toxicity following intrathecal or systemic gene-therapy administration (See pg. 2, line 18 of the specification).
It would have been obvious to combine the rAAV composition with a UBE3A gene of Arulanandam with the targeting sequences for miR183 in Hordeaux in order to prevent neuronal degradation following intrathecal administration, especially if AAVhu68 is used due to higher levels of toxicity compared to AAV9 when administered.
In view of the foregoing, claims 7, 8, 9, 10, and 11, taken as a whole, would have been prima facie obvious before the effective filing date.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Arulanandam et al., in view of Nambiar et al. (WO 2020/2232361 A1, published 11/05/2020, with an international filing date of 04/28/2020, publication of PCT/US20/30266, US application 17/605,868), as disclosed in the Information Data Sheet.
Regarding claims 13 and 14, Arulanandam teaches the composition of claim 1 as described above.
Arulanandam does not teach where the AAV capsid is a AAVrh91 capsid, or where the AAVrh91 capsid is generated from expression of the nucleic acid sequence of SEQ ID NO:17 or SEQ ID NO: 19.
Nambiar teaches recombinant AAV where the AAV capsid comprises a heterogenous population of AAVrh.91 vp1 proteins produced by expression from a nucleic acid sequence which encodes the predicted amino acid sequence of SEQ ID NO:1 or 3. SEQ ID NO: 3 of Nambiar comes from application 17/605,868 which has 100% identity of SEQ ID NO: 19 of the instant application.
Furthermore, Nambiar also teaches that in certain embodiments, the expression cassette contains at least one miRNA target sequence that is a miR-183 target sequence.
It would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have adapted the rAAV composition of Arulanandam with AAVrh91 disclosed in Nambiar. AAVrh91 is one of the AAVs used for expressing a transgene in motor neurons. Based off Fig. 10C, Nambiar shows AAVrh91 provides the strongest transgene expression in the spinal cord, which comprises of motor neurons. Furthermore, Nambiar discloses that AAVrh91 can be administered intrathecally (see pg. 6, line 4).
It would have been obvious that such combination of a rAAV with a UBE3A gene, with AAVrh91 and miR-183 could enhance the efficiency of transgene expression, which could be used for the treatment of Angelman syndrome.
In view of the foregoing, claims 13 and 14, taken as a whole, would have been prima facie obvious before the effective filing date
Double Patenting
Claims 1-3, 5, 6, and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of U.S. Patent No. US12516351B2 (reference patent), which claims priority to application 17/605,868. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 of the reference patent recites a rAAV having an AAVrh91 capsid comprising AAVrh91 capsid proteins (vp1, vp2, and vp3) produced by amino acids 1 to 173 of SEQ ID NO: 2 and a vector genome comprising a heterologous nucleic acid sequence operably linked to regulatory sequences that direct expression of a product encoded by the heterologous nucleic acid sequence in a target cell. Claim 2 of the reference patent discloses the nucleotide sequence encoding amino acids 1 to 736 of SEQ ID NO: 2 comprises of SEQ ID NO: 1 or 3. Furthermore, the composition comprising a recombinant AAV of claim 1 is suspended in a physiologically compatible carrier, buffer, adjuvant, and/or dilutant as disclosed in claim 4.
When reviewing the instant application, claim 1 recites a rAAV comprising an AAV capsid and vector genome comprising a UBE3A nucleic acid sequence or a nucleic acid sequence expressing UBE3A isoform 1 protein, further comprising of regulatory elements such as a neuron-specific promoter. This is indistinct from the “heterologous nucleic acid sequence operably linked to regulatory sequences” expressed in the rAAV recited in claim 1 of the reference patent.
With regards to the claim capsid protein sequences, SEQ ID NO: 17 and SEQ ID NO: 19 (claims 13-14 of instant application) have 100% identity to SEQ ID NO: 1 and 3 of the reference patent (claim 2).
Furthermore, claim 15 of the instant application and claim 4 of the reference patent both disclose the composition in suspension comprising of a physiologically compatible buffer, adjuvant, and/or dilutant.
Taken as a whole, it is obvious that the method discussed in the reference application could
apply to the composition and method of use in the instant application.
Claims 1-3, 5, 6, 13, and 14, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4, 9, and 10 of copending Application No. 18/040,648 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 of the reference application claims a method of delivering of a transgene to one or more target cells of the central nervous system (CNS) of a subject. The method comprises of administering to the subject a recombinant adeno-associated virus (AAV) vector comprising an AAVrh91 capsid and a vector genome comprising the transgene operably linked to regulatory sequences that direct expression of the transgene in the target cells of the CNS. Claim 4 recites that the AAV vector is delivered intrathecally. Claim 9 and 10 recite that the AAVrh91 capsid comprises a capdis protein producted by expression of nucleotide sequence of SEQ ID NO: 1 or 3.
Compared to the reference application, the composition of both instant and reference applications is an rAAV. Expanding on claim 1 of the instant application with dependent claims 2-3, 5, 6, 13, and 14, the rAAV is both AAVrh91 and administered intrathecally in both the instant and reference applications. Furthermore, SEQ ID NO: 17 of the instant application has 100% identity to SEQ ID NO:1 of the reference application and SEQ ID NO: 19 has 100% identity to SEQ ID NO: 3.
Furthermore, the expression of a transgene with regulatory sequences linked to the transgene administered to cells of the CNS reads on a composition expressing UBE3A (transgene) with regulatory elements (a neuron-specific or synapsin promoter as recited in claims 2 and 3) that target cells of the CNS (claim 19 recites administering the composition to neurons).
Taken as a whole, it is obvious that the method discussed in the reference application could
apply to the composition and method of use in the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No Claims are Allowed.
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/D.T.Y./Examiner, Art Unit 1635 /RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635