DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments to the claims and arguments filed on March 26, 2026 have been received and entered. Claims 17, 22-23, 26, 29, 31-33, 35-36 have been amended, while claims 1-16, 19-21, 24-25, 30, 34 have been canceled. Claims 40-49 are newly added. The objection to Claims 17, 19 and 20 is withdrawn in view of amendments to the claims.
Claims 17-18, 22-23, 26-29, 31-33, 35-48 and 49 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of (a) therapeutic gene (b) SMN1 and (c) spinal muscular atrophies and motor neuron disease as species in the reply filed on October 21, 2025 is acknowledged. Upon further consideration, election of species requirement between different species (b) gene and (c) for a single species of neuromuscular disorder is hereby withdrawn and all the non-elected species of gene and disorder are hereby rejoined with the elected specie of SMN 1 and SMA. Claims 17-18, 22-23, 26-29, 31-33, 35-48 and 49 read on elected species.
Priority
This application is a 371 of PCT/EP2021/061204 filed on 04/28/2021, which claims priority from foreign application EP 20305412.7 filed on 04/28/2020.
Claims 17-18, 22-23, 26-29, 31-33, 35-48 and 49 are under consideration.
Maintained & New--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 17-18, 22-23, 26-29, 31-33, 35-48 and 49 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 a method of expressing an heterologous gene of interest in a subject, said method comprising intravenously or directly injecting into CNS of the subject in need thereof, an effective amount of porcine adeno-associated virus (AAV) vector comprising (i) a capsid comprising a peptide-modified capsid protein, wherein the peptide modified capsid protein comprises the amino acid sequence of SEQ ID NO: 5 or a capsid comprising a peptide-modified capsid protein, wherein the peptide-modified capsid protein comprises the amino acid sequence as set forth in SEQ ID NO: 4, wherein said peptide is inserted between residues N569 and T570 of the capsid protein of AAVpo1 of SEQ ID NO: 1 and replaces all the residues from positions 567 to 569 and 570 to 572 of SEQ ID NO: 1;, and (ii) a heterologous gene encoding protein, thereby expressing gene in one or more of skeletal muscles, cortex, cerebellum or motor neuron,
does not reasonably provide enablement for delivering via any other route, using any other broadly claimed rAAV variant comprising an amino acid sequence having at least 98% with SEQ ID NO: 5 which comprises the amino acid sequences of any one of SEQ ID NO: 2 to 4 inserted between residues N567 and 5568 or N569 and T570 of the capsid protein of AAVpo1 as set forth in SEQ ID NO: 1, AAV delivering any gene of interest, delivering any therapeutic gene in an effective amount of rAAVpol1 or treating genus of nervous system disorders and neuromuscular disorders affecting the nervous system in a subject as embraced by the breadth of the claim. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Applicant disagree with the rejection arguing instant specification provides experimental data obtained with recombinant AAVpo1A1 capsid protein of SEQ ID NO: 5. This amino acid sequence comprises the peptide A1(MPLGAAG or SEQ ID NO: 2) flanked by G and A (corresponding to GMPLGAAG or SEQ ID NO: 3) and further flanked with QRG and QAA (corresponding to GQRGMPLGAAGAQAA or SEQ ID NO: 4) inserted between N569 and T570 and replacing all the residues from positions 567-569 (NSN) and 570-572 (THP) of AAVpo1 capsid protein of SEQ ID NO: 1. The Examples of the specification demonstrate that the AAVpo1A1 vector according to the claims is able to express high levels of the therapeutic transgene transcript and encoded protein in nervous system cells of the brain and spinal cord in vivo, following administration of the AAVpo1A1 vector to a subject (see Figures 6 and 8). Furthermore, the specification provides comparative data with AAV9 and AAVrh10 which are the gold standard for AAV gene therapy of nervous system diseases and neuromuscular diseases affecting the nervous system. These results demonstrate that AAVpo1A1 injected mice have therapeutic transgene expression levels in the nervous system (brain and spinal cord) that are at least equivalent if not higher than that of AAV9 and AAVrh10 injected mice (see Figure 6 and paragraph [0010] of the specification). These results also demonstrate that, just like AAV9 and AAVrh10, the AAVpo1A1 vector according to the claims can also be used as gene therapy vector for treating nervous system diseases and neuromuscular diseases affecting the nervous system. Applicants’ arguments have been fully considered, but are not found persuasive.
In response, as an initial matter, it is noted that contrary to applicant’s argument of providing evidence of using capsid protein of SEQ ID NO: 5, it is noted that claims 17-18, 22-23, 26-29, 31-33, 36-48 and 49 are not limited to SEQ ID NO: 5. To the extent, applicant’s argument pertain to insertion of SEQ I D NO: 2-3 of AAVpo1 capsid protein of SEQ ID NO: 1, it should be noted that claims as amended encompasses a capsid protein comprises an amino acid sequence that includes a variant that could include 5 to 7 additional modification including deletion, insertion, substitution at any site of viral capsid protein. However, the art teaches that change in even a single amino acid could result in loss of a functional virus. In this regard, Choi (Curr Gene Ther. 2005 June ; 5(3): 299–310) teaches engineering adeno-associated virus (AAV) capsid, in order to increase efficiency in targeting specific cell types that are non-permissive to wild type (wt) viruses and to improve efficacy in infecting only the cell type of interest (see abstract). However, Choi reported “Mutants generated in capsid mutation studies can be used to identify important domains of the capsid that are critical for viral assembly. Choi cite study from Wu that shows that alanine substitution at specific capsid positions carrying charged amino acids generated mutant viruses that were not able to assemble, In addition, a mutation at R-432 to A-432 alone can generate empty capsid (see page 12, para. 4). Michelfelder et al (PLoS ONE 2009;4:e 5122,pages 1-13, the abstract) teaches cell type-directed vector capsids can be selected from random peptide libraries displayed on viral capsids in vitro but so far this system could not easily be translated to in vivo applications (abstract). Xing ((PLoS Pathog 2025, 21(9): e1013533, pages 1-16) in a post filing publication support these assertions by stating “a diverse panel of AAV capsid variants previously identified from human clinical samples to discover candidates with enhanced liver tropism. In a high-throughput comparative analysis, although no capsid variant outperformed the parental AAV8 capsid in targeting the mouse liver, one variant exhibited markedly reduced liver tropism despite differing from AAV8 by only a single amino acid in the capsid protein. Further investigation demonstrated that introducing this single amino acid change into other AAV capsids similarly reduced their liver targeting (emphasis added). Notably, this amino acid resides in a structural region previously implicated in modulating liver tropism. These findings suggest a rational strategy to engineer liver-detargeting AAV vectors, potentially reducing liver-associated toxicity in systemic gene therapy applications targeting non-hepatic tissues (see page summary, page 2). In the instant case, claims are directed to use of an rAAV variant comprising an amino acid sequence having at least 98% with SEQ ID NO: 5 which comprises the amino acid sequences of any one of SEQ ID NO: 2 to 4 inserted between residues N567 and 5568 or N569 and T570 of the capsid protein of AAVpo1 as set forth in SEQ ID NO 1 that would comprises at least one or two amino acid additional mutations in said sequence, and wherein said at least one peptide is inserted anywhere with amino acid into a capsid from a porcine AAV serotype 1. In view of foregoing, it is apparent that the state of the art pertinent to searches for the desired rAAV vectors having the desired function among a library of random peptides had been carried out, were within the knowledge of the skilled, but the results were unpredictable. One cannot extrapolate the teachings of the specification to the scope of the claims because the skilled artisan cannot envision the structural function of the rAAV variants encompassed by these claims except the rAAV comprising a capsid comprising the amino acid sequence as of SEQ ID NO: 5. Further, Claims 17-18, 22-23, 26-29, 31-33, 36-49 do not even require the subject having any specific nervous or neuromuscular disease affecting the nervous system by administering any specific gene of interest to treat the disease. Further, recitation of wherein the therapeutic transgene is expressed in one or more of brain or spinal cord after systemic administration of said recombinant AAVpo1 vector particle is a conditional limitation that is not limiting the active step of administering the viral particle. It is noted that in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 38 USPQ 189 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Goodman, 29 USPQ2d 2010 (CA FC 1993); In re Fisher, 166 USPQ 18 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). One of skill in the art would have to perform undue experimentation to make and use the invention, without reasonable expectation of success.
In response to applicant’s argument that just like AAV9 and AAVrh10, the AAVpo1A1 vector according to the claims can also be used as gene therapy vector, the previous office action explicitly stated , the rejection in part is based on five separate issues (see page 5 , last para. and page 6, para. 1 of office action mailed on November 26, 2025). Applicant should note that claims are directed to a treating any nervous system disease or neuromuscular disease affecting the nervous system by gene therapy in a patient having the disease by administering to the patient via any route a therapeutically effective amount of a rAAV particle of the invention . As stated in previous office action, specification does not teach a method of in vivo delivery of a nucleic acid encoding any nucleic acid comprising a therapeutic transgene for treating the disease operably linked to a promoter functional in cells chosen from neurons or glial cells, wherein the therapeutic transgene is expressed in one or more of brain or spinal cord after systemic administration of said rAAV particle. The method encompasses treating genus of disease affecting the nervous system and the gene responsible for said disease are selected from the group comprising: Duchenne muscular dystrophy and Becker muscular dystrophy (DMD gene); Limb-girdle muscular dystrophies (DYSF, FKRP genes); Myotonic dystrophy type 1 (DMPKgene) and type 2 (CNBP/ZNF9 gene); Centronuclear myopathies (DNM2,BIN1 genes); Pompe disease (GAAgene); Glycogen storage disease III (AGL gene); Spinal muscular atrophy (SMN1, ASAH1 genes); Amyotrophic lateral sclerosis (SOD1, ALS2, SETX, FUS, ANG, TARDBP, FIG4, OPTN and others); Hereditary paraplegia (SPAST, SPG7); Charcot-Marie-Tooth, Type 4B1 (MTMR2), and Congenital myasthenic syndrome (CHAT, AGRN) subsequently limiting said gene responsible for the genetic neuromuscular disorder affecting the nervous system is selected from the group comprising: DMD, DYSF, FKRP, DNM2, BIN1, GAA, AGL, SMN1 and ASAHi1 genes. The new independent claims 42-43, 47-48 are drawn to use of gene encoding therapeutic selected from therapeutic antibodies or therapeutic RNA selected from interfering RNAs or antisense. It is noted that success of gene therapy for the treatment of treating any nervous system disease or neuromuscular disease will depend on the selection of the most appropriate therapeutic protein and its level of chronic expression in a predictable diseased animal model . In the instant case, neither specification nor instant specification provide evidence of expression of SMN1 protein or any other protein at a level sufficient in any predictable diseased animal model including SMA. Regarding claims 43 and 48, while it is recognized, that introduction of shRNA that is targeted to a specific gene may result in attenuation /inhibition of the targeted gene, the degree of attenuation and length of the time attenuation is achieved in not predictable (Caplen et al Gene 2000, vol. 252, 95-105). It is relevant to note that a recent study shows that siRNAs can induce silencing of non-target mRNAs with limited sequence complementarity, often via inter-actions with the 3’UTR. These interactions occur when short regions of the mRNA 30UTRcontain imperfect matches to the small RNA, triggering translational repression and/or degradation. In this way, depending on the sequence, one siRNA can potentially repress hundreds of transcripts. These off-target effects appear to be dosage dependent, and phenotypes derived from them can be dominant over the intended on-target phenotypes…Further, the artificial introduction of siRNAs or shRNAs into a target cell line can cause non-sequence-specific off-target effects. … Flooding the system with exogenous sequences can displace microRNAs from RISC. This can impair the functions of endogenous microRNAs, leading to alterations in gene transcript levels and consequently to off- target phenotypes (see page 576., col. 1, last para. to col. 2, Boettcher et al Molecular Cell, 2015, 58, 575-585). The guidance provided in the specification is limited to delivering a very high titer of recombinant AAVpolA1 and AAV9 vectors expressing SMNI at 8x1012vg/kg in a week old in C57BL/6 mice resulting in transduction of cells of spinal cord” (see para. 162 of the specification). There is no evidence on record that use of delivering via any route any of the broad genus of recombinant porcine adeno- associated virus (AAV) vector comprising any peptide-modified capsid protein would be predictive of expressing transgene, RNAi, siRNA or antibody showing any therapeutic effect in any predictable animal model as required by the claim. Bostick et al (Gene Therapy ; 2007, 14(22):1605-9) compared the level of transgene expression through different routes of administration (i.v. vs intra-arterial, all-in neonatal mice) and at different ages (neonatal vs adult, all through venous delivery). They highlight the importance designing age-specific gene therapy applications. Thus, given the breadth of the claims, it is apparent that one of skilled in the art would require the identification and characterization of different variant of porcine AAV for age specific and tissue specific expression with respect to testing their ability to infect cells of motor neuron or glial cells in neonatal or adult subject such that therapeutic protein in expressed in these cells at a therapeutic level in predictable animal model of SMA to make use of the invention without a reasonable expectation of success A showing that enough of a nucleic acid encoding a heterologous nucleic acid encoding plurality of different polypeptide, antibody that is expressed in the target cell (one or more of neuronal, glial or motor neuron), enough nucleic acid is incorporated into the target cells, that such nucleic acid is properly incorporated into such cells as DNA, enough mRNA is produced therefrom, and enough protein is produced that express gene of interest that have an effect on the target cells ((neuronal, glial or motor neuron)) and such effect is enough of an effect for a long enough period of time to treat plurality of nervous system disease or neuromuscular disease in a predictable animal model. An artisan would have to perform undue experiment to make and use the invention, without reasonable expectation of success.
In response to applicant’s argument that the systemic administration is not an essential feature of the claims, it should be noted that instant specification contemplates systemic, local or systemic combined with local administration of AAV particle of the invention that includes subcutaneous (SC), intramuscular (IM), intravascular such as intravenous (IV) or intraarterial; intraperitoneal (IP); intradermal (see para. 140 of the specification). The guidance provided in the specification is limited to an intravenous injection of vector expressing MTM1 is administered to a mutant mouse to show expression of MRM1 various muscle and organs (fig, 5 and 6). Likewise, instant specification further teaches intravenous injection of 8x10¹²vg/kg of AAVpo1A1 and AAV9 vectors expressing SMN1 at 4 weeks of age resulting in expression of SMN1 in muscle and organs (see fig.9). The guidance provided in the specification is limited to delivering a very high titer of recombinant AAVpolA1 and AAV9 vectors expressing SMNI at 8x1012vg/kg in a week old in C57BL/6 mice resulting in transduction of cells of spinal cord” (see para. 162 of the specification). There is no evidence on record that use of delivering via any route (intramuscular, subcutaneous or intradermal) any of the broad genus of recombinant porcine adeno- associated virus (AAV) vector comprising any peptide-modified capsid protein would be predictive of expressing transgene expression in brain and spinal cord that are at least equivalent if not superior to that of AAV9 vector as required by the claim. An artisan would have to perform undue experimentation to make and use the invention, without reasonable expectation of success.
Claim Rejections - 35 USC § 112-written description
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 17-18, 22-23, 26-29, 31-33, 35-39 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to a method of treating nervous system disorders and neuromuscular disorders affecting the nervous system by gene therapy in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a recombinant porcine adeno- associated virus (AAV) vector comprising a peptide-modified capsid protein, wherein the peptide-modified capsid protein comprises at least one peptide comprising the sequence MPLGAAG (SEQ ID NO: 2) or a variant comprising only one or two amino acid mutations in said sequence, and wherein said at least one peptide is inserted into a capsid from a porcine AAV serotype 1 (see claim 1). Dependent claims limit the recombinant porcine AAV vector is characterized by the combination of liver detargeting and transgene expression levels in different muscle groups, and in the brain and spinal cord that are at least equivalent if not superior to that of AAV9 vector, after systemic administration, in particular intravenous administration and wherein the peptide comprises the sequence GMPLGAAGA (SEQ ID NO: 3), or a variant comprising one or two amino acid deletions or substitutions in said sequence or the peptide comprises or consists of the sequence GQRGMPLGAAGAQAA (SEQ ID NO: 4).
In analyzing whether the written description requirement is met for the genus claim, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43). USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991
The claims encompass a genus of porcine AAVs comprising a peptide-modified capsid protein, wherein the peptide-modified capsid protein comprises at least one peptide comprising the sequence MPLGAAG (SEQ ID NO: 2) or a variant comprising only one or two amino acid mutations in said sequence intended for treating nervous system disorders, wherein the porcine AAV is characterized by liver detargeting and transgene expression levels in different muscle groups, and in the brain and spinal cord. Thus, the claim encompasses a variant comprising one or two amino acid mutations in the sequence at the either amino, carboxyl or both terminus of amino acid sequence MPLGAAG (SEQ IDN NO: 2) inserted anywhere within the capsid protein of porcine AAV1 of serotype 1. Additionally, claimed capsid protein comprises an amino acid sequence that includes at least one modification of deletion, insertion and/or replacement, substitution at any place within the viral capsid protein. Dependent claim limits the peptide-modified capsid protein comprises a sequence selected from the group consisting of the sequence SEQ ID NO: 5, and the sequences having at least 95%, identity with SEQ ID NO: 5. As such, insertion, deletion and/or substitution of up to about 35 amino acid that may be any one of the 20 amino acids at different positions and additionally there are numerous insertion and/or substitution positions on each capsid protein, and all of the aforementioned variables would bring the sum to genus of modified rAAVs variants, whose function is characterized by the combination of liver detargeting and transgene expression levels in different muscle groups, and in the brain and spinal cord that are at least equivalent if not superior to that of AAV9 vector intended for treating nervous system disorder were unknown and unpredictable.
The specification discloses that the "variant AAV capsid protein consisting of amino acid sequence as set forth in SEQ ID NOL 5 showing tropism for liver detargeting and transgene expression in different muscle groups, brain and spinal cord. However, the art teaches that change in even a single amino acid could result in loss of a functional virus. For instance, Choi et al (Curr Gene Ther. 2005 June ; 5(3): 299–310.) teach engineering adeno-associated virus (AAV) capsid, in order to increase efficiency in targeting specific cell types that are non-permissive to wild type (wt) viruses and to improve efficacy in infecting only the cell type of interest (see abstract). However, Choi reported “Mutants generated in capsid mutation studies can be used to identify important domains of the capsid that are critical for viral assembly. Choi cite study from Wu that shows that alanine substitution at specific capsid positions carrying charged amino acids generated mutant viruses that were not able to assemble, In addition, a mutation at R-432 to A-432 alone can generate empty capsid (see page 12, para. 4). Michelfelder et al (PLoS ONE 2009;4:e 5122,pages 1-13, the abstract) teaches cell type-directed vector capsids can be selected from random peptide libraries displayed on viral capsids in vitro but so far this system could not easily be translated to in vivo applications (abstract).Xing ((PLoS Pathog 2025, 21(9): e1013533, pages 1-16) in a post filing publication support these assertions by stating “a diverse panel of AAV capsid variants previously identified from human clinical samples to discover candidates with enhanced liver tropism. In a high-throughput comparative analysis, although no capsid variant outperformed the parental AAV8 capsid in targeting the mouse liver, one variant exhibited markedly reduced liver tropism despite differing from AAV8 by only a single amino acid in the capsid protein. Further investigation demonstrated that introducing this single amino acid change into other AAV capsids similarly reduced their liver targeting (emphasis added). Notably, this amino acid resides in a structural region previously implicated in modulating liver tropism. (see page summary, page 2). In view of foregoing, it is apparent that the state of the art pertinent to searches for the desired rAAV vectors having the desired function among a library of random peptides had been carried out, were within the knowledge of the skilled, but the results were unpredictable. One cannot extrapolate the teachings of the specification to the scope of the claims because the skilled artisan cannot envision the structural function of the rAAV variants encompassed by these claims except the rAAV comprising a capsid protein consisting of the amino acid sequence set forth as SEQ ID NO: 5.
There is no teaching or suggestion that any other substitution of any other spacer amino acid peptide insertion in any other order or combination at either amino or carboxyl or both terminus of amino acid sequence MPLGAAG (SEQ ID NO: 2) that would confer similar functions in an AAV virion that is characterized by the combination of liver detargeting and transgene expression in muscle and/or cells of CNS. In view of foregoing, it is apparent that the claims broad and generic, with respect to all possible porcine AAV and the peptide insertion comprising MPLGAAG at either amino, carboxyl or both terminus of amino acid sequence conferring activity in cells of involved in nervous system disorders and neuromuscular disorders that is characterized by the combination of liver detargeting and transgene expression levels in different muscle groups, brain and spinal cord as embraced by the claims. The possible structural variations are limitless to any amino acid sequence (or corresponding nucleic acid encoding sequence) that is at least 95% similar to SEQ ID NO: 5 and confers contemplated biological activity in nervous system disorders and neuromuscular disorders. The claims lack written description because there is no disclosure of a correlation between intended use in treating nervous system disorders and transgene expression levels in different muscle groups, brain and spinal cord and structure of the AAV variant particle beyond those variants as set forth in SEQ ID NO: 5 specifically disclosed in the examples in the specification. The specification lacks sufficient variety of species to reflect this variance in the genus showing contemplated biological activity. While having written description of a variant capsid protein consisting essentially of SEQ ID NO: 5 having contemplated biological activity identified in the specification and examples, the specification does not provide sufficient descriptive support for the myriads of variants embraced by the claims. There is no disclosure that teaches or suggests that any capsid sequence other than modified capsid protein consisting of the amino acid as set forth in SEQ D NO: 5 identified therein are capable of conferring expression in cells involved in nervous system disorders and neuromuscular disorders.
Overall, what these statements indicate is that the Applicant must provide adequate description of such core structure and function related to that core structure such that the Artisan of skill could determine the desired effect. The skilled artisan cannot envision the detailed chemical structure of the encompassed AAV variant particle other than AAV comprising a modified capsid consisting of SEQ ID NO: 5, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen lnc. v.Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
In conclusion, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that Applicant is in possession of an infectious AAV variant particle as broadly claimed for the contemplated biological activity at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Response to arguments
Applicant disagree with the rejection arguing design and production of peptide-modified AAV capsids with altered cell-specificity is a well-known technology that has been used successfully to modify the cell-specificity of various AAV serotypes including porcine AAV serotype 1 (AAVpo1); see cited references above; see also Grimm (WO 2019/207132). Therefore, the insertion strategy of any targeting peptide of interest into a given AAV capsid serotype such as AAVpo1 is disclosed in an enabling manner is known to a skilled person in the field of the invention (see cited references above; see also Grimm (WO 2019/207132), in particular Figure 7 (including legend) and Table 1). Table 1 of Grimm discloses that a cell-targeting peptide such as peptide A1 (MPLGAAG or SEQ ID NO: 2) is inserted between residues N567 and S568 (insertion site 1, second column of Table 1) or N569 and T570 (insertion site 2, fourth column of Table 1) of AAVpo1 capsid protein as specified in the amended claims. Table 1 further discloses that the three residues flanking the insertion site may be optionally modified: NQN-SNT (positions 565 to 567 and 568 to 570) and NSN-THP (positions 567 to 569 and 570 to 572). Figure 7 and its legend provide an explanation that the surrounding amino acids of the peptide insertion site are changed to enable a Sfil-mediated peptide insertion cloning. Figure 7 demonstrates that in AAVpo1A1, peptide A1 (underlined sequence MPLGAAG) is flanked by A and G (inserted amino acids) and GQR and QAA (exchanged amino acids, i.e. replacing NSN and THP). These amino acid modifications around the peptide insertion site are tolerated by the AAVpo1 capsid protein since the peptide A1-modified AAVpo1 capsid protein of SEQ ID NO: 5 which carries these modifications forms a functional AAV vector particle that is able to target nervous system cells efficiently in addition to muscle cells. Consequently, the teaching of the application and the knowledge of ordinary skill in the field of the invention provide sufficient information to modify the peptide-modified AAVpo1 capsid of SEQ ID NO: 5 and obtain a functional variant having at least 98% identity with SEQ ID NO: 5. For all these reasons a person skilled in the field of the invention can easily carry out the claimed invention. Applicants’ arguments have been fully considered, but are not found persuasive.
In response, it is noted that the claimed genus of capsid protein comprising an amino acid sequence having at least 98% with SEQ ID NO: 5 which comprises the amino acid sequences of any one of SEQ ID NO: 2 to 4 inserted between residues N567 and 5568 or N569 and T570 of the capsid protein of AAVpo1 as set forth in SEQ ID NO: 1, wherein the rAAV particle exhibits expression in one or more of brain or spinal cord after systemic administration of said recombinant AAVpo1 vector particle. The genus of variant AAV po1 capsid protein encompass a 2% difference in amino acid sequence of SEQ ID NO: 5 (which is 725 amino acids in length) that allows for 14 amino acid differences comprising SEQ ID NO: 2 (7aa) or SEQ ID NO:3 (9 aa). As such, insertion, deletion and/or substitution of up to 5 to 7 amino acid that may be any one of the 20 amino acids at different positions and additionally there are numerous insertion and/or substitution positions on each capsid protein, and all of the aforementioned variables would bring the sum to a genus of modified rAAVs variants, whose function of enhanced expression in one or more of brain or spinal cord after systemic administration were unknown and unpredictable in terms of their expression in brain or spinal cells.
The previous office action explicitly reported unpredictability in the relevant art with respect to the structural variation of the capsid and changes in infectivity on a specific cell type as taught by cited references, such as Choi having the aforementioned knowledge would not reasonably predict which and how many of the genus of variants would have enhanced expression in brain or spinal cells. Choi et al (Curr Gene Ther. 2005 June; 5(3): 299-310.) reported “Mutants generated in capsid mutation studies can be used to identify important domains of the capsid that are critical for viral assembly. Choi cite study from Wu that shows that alanine substitution at specific capsid positions carrying charged amino acids generated mutant viruses that were not able to assemble, In addition, a mutation at R-432 to A-432 alone can generate empty capsid (see page 12, para. 4). Hence, when the specification only teaches which random peptide libraries one can start the search for a rAAV virion having a variant capsid and conferring increased expression in neuron or muscle cells infectivity, it calls for a search of sequences having the desired function (emphasis added), however, it fails to show that the applicant was in possession of the claimed genus of variants showing claimed biological activity. It should be noted that while different peptide sequence having common core were inserted in the claimed region of AAVpo1 as set forth in SEQ ID NO: 1, only one SEQ ID No. 5, had been proven to enhance infectivity in brain or spinal cells. Here, the rejection under written description is based on the failure of the specification establishing the relationship between the structure and function of the genus rAAV virions having modified AAV capsids embraced by the breadth of the claim, not whether specification contains description of peptide insertion into AAV virion capsids. In view of foregoing, one of skill in the art would conclude applicant did not possess the invention as it is claimed.
Withdrawn Claim Rejections - 35 USC § 112
Claim 18 was rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Applicant’s amendments to claim 18 obviates the basis of the rejection.
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 17-18, 22-23, 26-29, 31-33, 36 and 37 remain rejected and claims 38-41, 43, 45, 46, 48 and 49 are also rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Grimm (WO2019207132, dated 10/31/2019, IDS) as evidenced by Bello (WO2009030025, dated 05/14/2009, IDS).
Claim interpretation: Instant rejection is applied to the extent prior art teaches the same active method step of intravenously delivering the porcine AAV encoding a gene of interest to subject and not necessarily to a method of treating any condition.
Regarding claims 17, 22-23, 27, 36-41, 45, Grimm teaches a method, comprising intravenously administering to a subject a recombinant porcine adeno- associated virus (AAV) vector comprising a peptide-modified capsid protein, wherein the peptide-modified capsid protein comprises at least one peptide comprising the sequence GMPLGAAGAQAA (SEQ ID NO: 9) that has 100% sequence identity to SEQ ID NO: 4 (see example 3, lines AAV pol1A1) resulting in expression in muscle tissue including skeletal muscle. Grimm teaches the peptide replaces all the residues from positions 565-567 to GQR and 568-570 to QAA relative to AAV pol1 (see fig. 7 below) as set forth in SEQ ID NO: 1 as evident from Bello. It is further disclosed that AAVp1_A1 has characteristics similar to AAV9 that includes expression in brain and muscle cells (see fig. 1, 3, page 7/23). Grim further teaches inserting GMPLGAAGA between 567 and 569 and the resulting modified capsid would comprise an amino acid sequence that that is 100% identical to SEQ ID NO: 5 (see fig. 7).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Grimm teaches using ubiquitous promoter including RSV and CMV that are functional in glial cells (see page 18, line 24). The term functional is broadly interpreted as ubiquitous non-specific expression in many cells including glial cells and not limited to any cell specific expression.
With respect to claim 18, teaches porcine AAV is characterized by liver detargeting and expression in muscle and minimal expression in brain (see fig. 1 and 7). It is further disclosed that the peptide is inserted between residues N567 and S568 of AAVpol1 VP1 (table 1, 2). It is noted that wild type AAVpol1 VP1 sequence was known in art as evidence from Bello who discloses SEQ ID NO: 24 that has 100% sequence identity to SEQ ID NO: 1 (see sequence search report).
Query Match 100.0%; Score 75; Length 21;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GQRGMPLGAAGAQAA 15
|||||||||||||||
Db 4 GQRGMPLGAAGAQAA 18
,
With respect to claim 24, 26-27, 31-33, Grimm teaches that the porcine AAV vector comprises a vector particle packaging a polynucleotide that is a functional wild type version of a gene involved in Duchenne muscular dystrophy (DMD gene) or FKTN gene (see page 11, line 20, 28, page 14, lines 26-27. claim 25 of ‘132).
Regarding claims 43, 48, Grimm teaches that the porcine AAV particle comprises a guide RNA for genome editing (see page 14, line 31).
Regarding claims 28-29. Grimm teaches that the subject has a disease selected from myoclonus dystonia and a mitochondrial myopathy that is genetic neuromuscular disease affecting nervous stem (see page 14, line 20). Grimm further teaches that subject has a congenital muscular dystrophy (see page 14, line 29).
New-Claim Rejections - 35 USC § 103- necessitated by amendments
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.
Claims 40-49 are rejected under 35 U.S.C. 103 as being unpatentable over Grimm (WO2019207132, dated 10/31/2019, IDS) as evidenced by Bello (WO2009030025, dated 05/14/2009, IDS) as applied above and further in view of Ising (J Exp Med . 2017 1;214(5):1227–1238)/Buj et al (US20170071972, dated 03/16/2017).
Claim interpretation: Instant rejection is applied to the extent prior art teaches the same active method step of intravenously delivering the porcine AAV encoding a gene encoding RNAi or antibody to subject and not necessarily to a method of treating any condition. Recitation of a promoter functional in neurons and/or glial cells is interpreted to encompass any ubiquitous promoter that is functional in all cells
Regarding claims 40, 45, Grimm teaches a method, comprising intravenously administering to a subject a recombinant porcine adeno- associated virus (AAV) vector comprising a peptide-modified capsid protein, wherein the peptide-modified capsid protein comprises at least one peptide comprising the sequence GMPLGAAGAQAA (SEQ ID NO: 9) that has 100% sequence identity to SEQ ID NO: 3 (see example 3, lines AAV pol1A1) resulting in expression in muscle tissue including skeletal muscle. Grimm teaches the peptide replaces all the residues from positions 565-567 to GQR and 568-570 to QAA relative to AAV pol1 (see fig. 7 below) as set forth in SEQ ID NO: 1 as evident from Bello. Grim further teaches inserting GMPLGAAGA between 567 and 569 and the resulting modified capsid would comprise an amino acid sequence of GQR GMPLGAAGAQAA that is 100% identical to SEQ ID NO: 5 (see fig. 7 and sequence search result).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Grimm teaches using ubiquitous promoter including RSV and CMV that are functional in glial cells (see page 18, line 24). The term functional is broadly interpreted as ubiquitous non-specific expression in many cells including glial cells and not limited to any cell specific expression.
With respect to claim 18, teaches porcine AAV is characterized by liver detargeting and expression in muscle and minimal expression in brain (see fig. 1 and 7). It is further disclosed that the peptide is inserted between residues N567 and S568 of AAVpol1 VP1 (table 1, 2). It is noted that wild type AAVpol1 VP1 sequence was known in art as evidence from Bello who discloses SEQ ID NO: 24 that has 100% sequence identity to SEQ ID NO: 1 (see sequence search report).
Query Match 100.0%; Score 75; Length 21;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GQRGMPLGAAGAQAA 15
|||||||||||||||
Db 4 GQRGMPLGAAGAQAA 18
,
With respect to claim 24, 26-27, 31-33, Grimm teaches that the porcine AAV vector comprises a vector particle packaging a polynucleotide that is a functional wild type version of a gene involved in Duchenne muscular dystrophy (DMD gene) or FKTN gene (see page 11, line 20, 28, page 14, lines 26-27. claim 25 of ‘132).
Regarding claims 43, 48, Grimm teaches that the porcine AAV particle comprises a guide RNA for genome editing (see page 14, line 31). It is further disclosed that polynucleotide comprises a nucleic acid sequence reducing or abolishing expression of a disease mediating variant of a gene from the genome of a subject. Thus, preferably, the polynucleotide comprises an expressible construct mediating expression of an siRNA, miRNA, ribozyme or similar molecular tool known to the skilled person (see page 13, lines 28-32)
Regarding claims 28-29. Grimm teaches that the subject has a disease selected from myoclonus dystonia and a mitochondrial myopathy that is genetic neuromuscular disease affecting nervous stem (see page 14, line 20). Grimm further teaches that subject has a congenital muscular dystrophy (see page 14, line 29). Grimm differs from claimed invention by not disclosing (i) therapeutic proteins is a therapeutic antibody (limitation of 42, 47).
However, before the effective filing date of instant application, it was routine in prior art to use AAV to express gene of interest encoding scFV Ising teaches anti-tau scFvs in the brain of a mouse model of tauopathy by AAV-mediated gene transfer (see fig. 2). Likewise, Buj teaches delivering a molecule to the central nervous system (CNS) by infusing AAV encoding capable of correcting a defect in a native protein, e.g. an antisense RNA (siRNA, shRNA) inducing exon skipping/inclusion or silencing gene expression, a microRNA (see para. 84). It is further disclosed that vector comprises CMV or CNS specific promoter, such as the P0, NSE, SYN1, Hb9 or Thy-1 promoter (see para. 108, 109).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the method of Grimm by substituting transgene in the AAVpol1 with nucleic acid encoding scFV or RNAi such as one disclosed in Ising or Buj, in the method of expressing transgene in cells of CNS, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of skill in the art would have been expected to have a reasonable expectation of success in expressing scFV or RNAI in the CNS using AAV particle disclosed in Grimm because prior art successfully reported delivering gene of interest in CNS as evident from the teaching of Grimm and Ising. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Response to arguments
Applicant disagree with the rejection arguing Grimm fails to disclose an AAVpo1A1 vector comprising a nucleic acid comprising a therapeutic transgene for treating a disease operably linked to a promoter functional in neurons and/or glial cells according to pending claims 17, 40 or 45. Grimm fails also to disclose the use of a peptide-modified AAV vector for treating a nervous system disease or neuromuscular disease affecting the nervous system according to present claim 17. Grimm fails also to disclose the use of a peptide-modified AAV vector for gene therapy of a disease affecting the nervous system or the nervous system according to present claim 40. Grimm fails to disclose the use of a peptide-modified AAV vector for expressing a therapeutic transgene in nervous system cells of a subject in need thereof according to present claim 45. Grimm fails also to disclose that the transgene is expressed in one or more of brain or spinal cord after systemic administration of the recombinant AAVpo1A1 vector particle. Grimm fails also to disclose that the expression level of the transgene is increased in one or more of brain or spinal cord after systemic administration of the recombinant AAVpo1A1 vector particle compared to AAVpo1 vector particle. Grimm fails to disclose the claimed method of expressing a therapeutic transgene in nervous system cells of a subject in need thereof according to claim 40, comprising administering to the subject a recombinant porcine adeno-associated virus serotype 1 (AAVpo1) vector particle comprising a peptide-modified capsid protein comprising a peptide of SEQ ID NO: 4 inserted between residues N569 and T570 of AAVpo1 capsid protein of SEQ ID NO: 1 and replacing all the residues from positions 567 to 569 and 570 to 572 of SEQ ID NO: 1; and a nucleic acid comprising a therapeutic transgene operably linked to a promoter functional in neurons and/or glial cells.
In response, it should be noted that previous office action explicitly stated that instant rejection is applied to the active method step that is commensurate with scope indicated in the office action. The rejection pertains to extent art teaches the same active method step of intravenously delivering the porcine AAV encoding a gene of interest to a subject in need thereof and not necessarily to a method of treating any condition as argued by the applicant (see scope of the enablement rejection). Applicant do not point to the difference in active method step disclosed in prior art of Grimm to the method as claimed that recite a single step of administering to the patient a therapeutically effective amount of a recombinant porcine adeno-associated virus (AAV) serotype 1 (AAVpo1) vector of the invention. None of the independent claims limit the subject having any specific neuromuscular disease affecting the nervous system by administering any specific gene of interest to treat the disease. Further, recitation of wherein the therapeutic transgene is expressed in one or more of brain or spinal cord after systemic administration of said recombinant AAVpo1 vector particle is a conditional clause. The active method step does not require a systemic administration of the virus of the invention and therefore administering step is not limiting to the systemic route.
In response to applicant’s argument that Grimm fails to teach a particle comprising a peptide-modified capsid protein comprising a peptide of SEQ ID NO: 4 inserted between residues N569 and T570 of AAVpo1 capsid protein of SEQ ID NO: 1, it should be noted that Grimm explicitly teaches intravenously administering to a subject a recombinant porcine adeno- associated virus (AAV) vector comprising a peptide-modified capsid protein, wherein the peptide-modified capsid protein comprises at least one peptide comprising the sequence GMPLGAAGAQAA (SEQ ID NO: 9) that has 100% sequence identity to SEQ ID NO: 4 (see example 3, lines AAV pol1A1) resulting in expression in muscle tissue including skeletal muscle. Grimm teaches the peptide replaces all the residues from positions 565-567 to GQR and 568-570 to QAA relative to AAV pol1 (see fig. 7 below) as set forth in SEQ ID NO: 1 as evident from Bello resulting in a amino acid sequence that would be 100% identical to SEQ ID NO: 5. .
PNG
media_image1.png
200
400
media_image1.png
Greyscale
In response to applicant’s argument regarding limitation of transgene operably linked to a promoter functional in neurons and/or glial cells, is should be noted that Grimm teaches using ubiquitous promoter including RSV and CMV that are functional in glial cells (see page 18, line 24). The term functional is broadly interpreted as ubiquitous non-specific expression in many cells including glial cells and not limited to any cell specific expression. This is further evident form the teaching in Pellissie et al (Molecular Therapy — Methods & Clinical Development (2014) 1, 14009, 1-9, previously cited as pertinent art for providing evidence without relying on the rejection ).
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants' arguments are not compelling and do not overcome the rejection of record.
Examiner’s note: Should applicant amend the independent claim 17 to include the limitation of claim 35, specifying the capsid comprising the sequence of SEQ ID NO: 5 and specific gene (SMN1) in a method of expressing SMN1 in neuron and glial cell of a subject in need thereof, instant obviousness rejection may be overcome pending further consideration.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Pellissie et al (Molecular Therapy — Methods & Clinical Development (2014) 1, 14009, 1-9) Minimal cytomegalovirus (CMV) promoter allowed expression of full-length CRB1 protein in Müller glial cells.
Tulalamba et al (Gene Therapy, 2019, , 27, 170-179) teaches a method of expressing gene of interest in a muscle and/or cells of CNS, said method comprising intravenously administering 4 × 1010 recombinant AAVpo1 or AAV9 particles comprising a capsid and gene of interest (luciferase) that is operably linked to a muscle specific SPc5-12 promoter to a subject (see page 177, col. ,1, last para.), wherein said administration results in expression of luciferase in skeletal muscle (see page 171, col. 2, para. 1).
Bello et al (Scientific report, 2014, 4 : 6644, 1-11) teaches intravenous injection of porcine AAV genomes in the brain following AAVpo4-LacZ and –po6-LacZ I injection, wherein the porcine AAV is able to traverse the blood-brain barrier and transduce cells in the CNS (see page 5, col. 2, last para. to page 7, col. 1, fig. 8).
Grimm (WO2018189244, 10/18/2018) teaches identification and use of AAV vector with improved infection of selected target cells, wherein said vectors are characterized by a strain specific polypeptide and a peptide inserted into said capsid polypeptide. It is further disclosed that peptide is inserted after amino acid 567 or 569 of in AAVpo1 (see Abstract, page 5, lines 1 and 2, page 7, line 10, Table 1 ).It is further disclosed that the peptide may replace all the residue from N567- and S568 or N569 or T570 of AAVpol1 VP1 (table 1).
Aguti et al ( Expert Opin Biol Ther. 2018 Jun;18(6): 681–693, IDS) teaches AVV mediated gene therapy in neuromuscular disorder (Abstract). In Table 1 a list of AAV gene therapy clinical trials for DMD/BMD, SMA and XLMTM is depicted: It is noted that scAAV9 expressing SMN1 under the control of a chicken beta-actin promoter and rAAV8 expressing MTM1 under a desmin promoter detargeted from liver (see Abstract).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571)272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANOOP K SINGH/ Primary Examiner, Art Unit 1632
Prosecution Insights