DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment of 1/9/26 has been entered in full. Claims 11-33 are amended. Claims 1-33 are pending.
The objection to claims 11-33 under 35 CFR 1.75(c) as being in improper form because multiple dependent claim cannot depend from any other multiple dependent claims is withdrawn in view of the amendments to the claims.
Election/Restrictions
As amended, claims 11-33 now depend solely from claim 2, and further limit the method of administering a BAG3 encoding nucleic acid. As such, claims 11-33 belong to Invention I as set forth in the restriction requirement mailed on 9/10/25.
Applicants' election with traverse of Invention I, drawn to a method of treatment by administering a BAG3-encoding nucleic acid, in the reply filed on 1/9/26 is acknowledged. Applicants’ arguments are directed solely to the election of species requirement. As such, with respect to the election of the inventive group, because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Applicants’ election with traverse of “Parkinson’s disease, other central nervous system inflammation” as the species of inflammation in the reply is also acknowledged. Because “Parkinson’s disease” and “other central nervous system inflammation” are by definition two different species, for the purposes of advancing prosecution the elected species is held to be the first recited species, which is “Parkinson’s disease”.
The traversal is on the ground that “it would not be an undue burden on the patent office to examiner all unelected species with the elected species” (page 7).
This argument has been fully considered but is not found persuasive because, as set forth in the restriction requirement at pages 5-6, each species of inflammation is mutually exclusive as evidenced by the different diagnostic criteria defining each type of inflammation, and there is a search burden for the patentably distinct species because the species each require a different field of search; i.e., employing a different set of search queries for each type.
The specification does not teach any link between TNF signaling and Parkinson’s Disease. As such, claims 1, 4, 17 and 18 are directed to non-elected species. Claim 6 does not recite central nervous system inflammation encompassing Parkinson’s, and as such is directed to non-elected species. The specification further does not teach that Parkinson’s patients have reduced expression of BAG3 or mutations in BAG3. As such, claims 19, 26 and 27 are directed to non-elected species. Therefore, claims 1, 4, 6, 17-19, 26 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 2-3, 5, 7-16, 20-25 and 28-33 are under consideration.
Specification
The disclosure is objected to because of the following informalities:
---The title of the invention is not descriptive because it is not clear what is meant by “BAG3 Methods and Uses”. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Method for Treating Inflammation With BAG3”.
---On page 15, in the first line of the last paragraph, “anthanogene” should be “athanogene”.
---On page 16, line 3, “invention can be a can be a variant” should be “invention can be a variant”.
Appropriate correction is required.
Claim Objections
Claims 2-3, 5, 7-16, 20-25 and 28-33 are objected to for the following informalities:
Claims 2-3, 5 and 7-10 are objected to for encompassing the subject matter of non-elected inventive groups; specifically Inventions II, III and IV of the restriction requirement mailed on 9/10/25. See page 2.
In each of claims 2-3, 5 and 7-10, “BCL2-associated athanogene 3 (BAG3) encoding nucleic acid” is missing an article; i.e., “a BCL2-associated athanogene 3 (BAG3) encoding nucleic acid”.
In each of claims 3 and 7, line 2 of each, “ofBCL2” should be “of BCL2”.
In claim 9, line 4, “alpha- synuclein” should be “alpha-synuclein”.
In each of claims 12 and 21, line 3 of each, each of the promoters starting with “bicistronic promoter” is missing an article; i.e., “a bicistronic promoter”. Compare with “a constitutive promoter” in lines 2-3.
In claim 14, line 3, each of the vectors starting with “cytomegalovirus vector” is missing an article; i.e., “a cytomegalovirus vector”. Compare with “a coxsackie virus vector” in lines 2-3.
In claim 14, line 3, “Epstein- Barr” should be “Epstein-Barr”.
In claim 15, line 3, “AAV7m” should be “AAV7,”.
In claim 15, line 3, “AAV1 1” should be “AAV11”.
In claims 28-33, the exponents should be written in superscript; e.g., “1.0x1014”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-3, 5, 7-16, 20-25 and 28-33 are 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 pre-AIA the applicant regards as the invention.
Claims 2-3, 5 and 7-10 are each indefinite because each is directed to both a method of using a product and a formulation comprising said product. As such, this renders each claim a single claim which claims both a product and a method step of using said product, which per MPEP 2173.05(p) is indefinite under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
In claim 14, lines 3-4, “hepatitis virus vectors” is indefinite because it is unclear how “a viral vector” (singular) of parent claim 13 can comprise multiple vectors.
Claim 20 recites the limitation “the inflammation or inflammatory response” in line 2. There is insufficient antecedent basis for this limitation in the claim. Specifically, parent claim 2 only refers to inflammation and not an inflammatory response, and thus does not provide antecedent basis for the alternative in the dependent claims directed to “the … inflammatory response”.
Claims 26 and 27 each recite the limitation “the patient or human” in line 2. There is insufficient antecedent basis for this limitation in the claim. Specifically, parent claim 2 only refers to a patient, and not a human, and thus does not provide antecedent basis for the alternative in the dependent claims directed to “the … human”.
In each of claims 28-33, the recitation “or formulated” in line 2 is indefinite because as amended the claims are no longer directed in the alternative to a formulation, and it is unclear how the act of being “formulated” further limits the method of the parent claim, which does not include a step of formulating.
The remaining claim(s) included in the rejection are dependent claims that depend from one of the claims rejected above, and encompass the same indefinite subject matter.
Claim Rejections - 35 USC § 112(a), 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 2-3, 5, 7-16, 20-25 and 28-33 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Per MPEP 2163, 35 U.S.C. 112(a) requires, “separate and distinct from the enablement requirement”, that the “specification shall contain a written description of the invention…” (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
The claimed invention is a method; specifically a method of treating of inflammation that requires administering a nucleic acid encoding a BAG3 protein or BAG3 peptide. The elected species of inflammation under consideration is Parkinson’s disease. The specification teaches that BAG3 (Bcl-2 associated athanogene) “is a cytoprotective polypeptide that competes with Hip-1 for binding HSP 70” (page 15), elsewhere described as “heat shock protein 70” (page 1).
The specification at page 15 identifies the amino acid sequence of the human BAG3 that is known in the prior art as SEQ ID NO: 1 (575 amino acids), encoded by a nucleic acid sequence of SEQ ID NO: 2 (2,608 nucleic acids). On pages 15-16, SEQ ID NO: 3 (575 amino acids), SEQ ID NO: 4 (575 amino acids), SEQ ID NO: 5 (574 amino acids), and SEQ ID NO: 6 (575 amino acids) are taught to represent other BAG3 sequences known in the prior art without further description. Sequence alignment between SEQ ID NO: 1 and each of these sequences reveals that SEQ ID NO: 3 and 6 are 100% identical to SEQ ID NO: 1; SEQ ID NO: 4 differs from SEQ ID NO: 1 by one amino acid substitution; and SEQ ID NO: 5 differs from SEQ ID NO: 1 by one amino acid substitution and 1 amino acid deletion. No information is provided as to whether the mutated BAG3 proteins of SEQ ID NO: 4 or 5 retain functionality.
The specification further teaches that a BAG3 polypeptide of the invention “can be a variant of a polypeptide described herein, provided it retains functionality”. The specification further teaches that the terms ““polypeptides,” “proteins” and “peptides” encoded by the “polynucleotide sequences,” include full-length native sequences, as with naturally occurring proteins, as well as functional subsequences, modified forms or sequence variants so long as the subsequence, modified form or variant retains some degree of functionality of the native full-length protein”.
In view of the language recited in the claims, and the teachings of the specification, the claims encompass naturally-occurring BAG3 polypeptides, such as the human protein represented by SEQ ID NO: 1, as well as variants having one or more mutations in the naturally-occurring sequence, without limit. Furthermore, both the terms “BAG3 polypeptide” and “BAG3 peptide” each encompass fragments of BAG3 that retain the activity of the full-length protein. As such, the claims encompass use of a vast genus of BAG3 protein variants. As noted above, the human BAG3 consists of 545 amino acids, and thus variants of this sequence include those in which each position is replaced with any of the other 19 natural amino acids, either singly or in combination with mutations at each of the other positions. Even if just single amino acid substitutions are considered, the genus of potential structures encompasses 10,925 variants. Substitutions at each of the 525 residues of the protein includes up to 19575 variants, or 1.9 x 10735 variants. The genus of structures further includes every possible fragment of BAG3 in combination, with or without substitution mutations at each position.
As quoted above, the specification further indicates that variants of BAG3 should require functionality of the naturally-occurring protein, and the claimed method necessarily requires such for successful treatment. Thus, the product employed by the claimed method is defined structurally by its amino acid sequence, and functionally by its ability to function as a native BAG3 protein. However, a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition".
The prior art appreciates that "Mutations … are generally destabilizing, and can reduce protein … fitness" and "In general, more comprehensive understanding of how mutations affect protein fitness within living cells is needed, including their combined effects on function, thermodynamic and kinetic stability, and clearance through aggregation and degradation" (pg 602 of Tokuriki et al, 2009, Current Opinion in Structural Biology. 19: 596-604). The prior art also appreciates that "the range of possible SNV [single nucleotide variation] effects at the protein level are significantly greater than currently assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge" (pg 18 of Bhattacharya et al, 2017. Plos One. 12(3): e0171355, pages 1-22 as printed). Thus, knowledge of the sequence of a protein (e.g., a BAG3 protein having the amino acid sequence of SEQ ID NO: 1) is not sufficient for the skilled artisan at the time of the effective filing date to predict which substitution mutations will result in a protein having the required target activity.
Written description for a genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). “[A] sufficient description of a genus … requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69). A description of a single species defined by its amino acid sequence is not representative of a genus encompassing thousands or more members having different structures. Per MPEP 2163, "A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")
In the instant case, the specification provides very limited guidance as to the nature of which members of the vast genus of BAG3 amino acid sequences encompassed by claim 1 that will have the required functionality. As described above, the specification provides the naturally-occurring human sequence of BAG3, as well as two variant sequences with alterations at one or two positions (SEQ ID NO: 4 and 5). However, the specification does not even teach whether these variants retain the activity of the native BAG3 protein. Thus, the specification only describes a single example of a BAG3 protein having the functionality required for use in the claimed method of treatment; i.e., the amino acid sequence of SEQ ID NO: 1. While this sequence meets the written description requirement, it does not provide any description of other sequences in the vast genus of encompassed structures that also have the required functionality in binding to a particular target. The specification further does not describe any positions in BAG3 where amino acid mutations can be made without altering the activity of the protein.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
Therefore, only a method of claims 2-3, 5, 7-16, 20-25 and 28-33, wherein the nucleic acid encodes a BAG3 protein having the amino acid sequence of SEQ ID NO: 1, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Note on Prior Art Rejection(s)
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 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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2, 3, 5, 7-11, 13, 20-21 and 24-25 are rejected under 35 U.S.C. 103(a) as being unpatentable over Cao et al (2017. Neurobiology of Aging. 104-115), and further in view of Sandoval (2021. J Parkinson’s Dis. 11(Suppl 2): S189-S197. Pre-press publication date of 6/4/21). The earliest date to which the instant application claims priority is 10/22/21.
Claims 2 and 3 each encompass a method for treating a patient suffering from inflammation comprising administering an agent that increases an amount of BAG3 encoding nucleic acid, thereby treating inflammation. The elected species of inflammation under consideration is Parkinson’s disease, which is an inflammatory response that affects the central nervous system, as recited in dependent claims 5 and 20 in the alternative.
Cao teaches that “Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and characterized by the death of dopaminergic neurons and formation of Lewy bodies in the substantia nigra pars compacta … Although its etiology remains elusive, many studies demonstrate that both genetic and environmental factors result in the formation of inclusion body, which is mainly composed of misfolded SNCA/α-synuclein and other ubiquitinated proteins” (page 104). Cao reports that overexpression of BAG3, using a BAG3-encoding plasmid (page 106), reduced accumulation of SNCA (alpha-synuclein) in cells (page 114). Cao teaches that “BAG3 attenuates SNCA accumulation via enhancing macroautophagy activity” (page 114). Cao further teaches “our findings reveal that BAG3 may become a therapeutic target for PD [Parkinson’s disease] treatment” (page 115). Cao does not expressly teach administering a BAG-encoding nucleic acid to a patient with Parkinson’s disease.
Sandoval, in a review titled “Gene Therapy to Modulate Alpha-Synuclein in Synucleinopathies” teaches that “point mutations and gene multiplications of SNCA alter the aggregation potential of α -Syn and cause PD in a dose-dependent manner … thus, indisputably linking α -Syn to the disease process” (page S189) and “[b]ased on the assumption that α-Syn pathology is a cause and not a consequence of disease, anti-Synuclein strategies have emerged as the indisputable disease-modifying therapeutic strategy” (page S190). Sandoval further teaches that “CNS gene therapy has made great strides, and PD has a rich history utilizing gene therapy, with 25 trials currently listed on clinicaltrials.gov involving PD, albeit none have been aimed at modulating α-Syn” (page S194).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the BAG3-encoding nucleic acid taught by Cao and administer it to a patient with Parkinson’s disease for gene therapeutic treatment of PD as taught by Sandoval. The person of ordinary skill in the art would have been motivated to make such a change in order to treat Parkinson’s disease, and would have had a reasonable expectation of success in view of the results observed by Cao that BAG3 overexpression can reduce alpha-synuclein levels. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007). The modified method of treatment obvious over the teachings of Cao in view of Sandoval meets the limitations of claims 2-3, 5 and 20.
In claims 7 and 8, the recitations of “for modulating PARP1 levels, expression or activity” (claim 7) and “to reduce, inhibit, or decrease PARP1 levels” (claim 8) have been considered in the context of the entire claim, and are each interpreted as an intended use for the method because each does not result in a manipulative difference between the method as defined by the steps and a prior art method teaching the same steps. See MPEP 2111.02. Likewise, each concluding “thereby” clause has been fully considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). As such, with respect to anticipation by the prior art, claims 7 and 8 each encompass a method comprising administering to a patient an amount of BAG3 encoding nucleic acid. As such, the method obvious over the teachings of Cao in view of Sandoval that meets the limitations of claims 2, 3 and 5 also meets the limitations of claims 7 and 8.
Claims 9 and 10 encompass a method to decrease amounts of alpha-synuclein (claim 9) or decrease a symptom of Parkinson’s disease (claim 10) comprising administering to a patient an amount of BAG3 encoding nucleic acid, thereby decreasing amount of alpha-synuclein (claim 9) or a symptom of Parkinson’s (claim 10). The teachings of Cao et al are directed to the ability of BAG3 to reduce alpha-synuclein accumulation, which is a decrease of the amount of alpha-synuclein, represent a decrease in a symptom of Parkinson’s disease. As such, the method obvious over the teachings of Cao in view of Sandoval that meets the limitations of claims 2, 3 and 5 also meets the limitations of claims 9 and 10.
Claim 11 encompasses a method of claim 2 wherein the BAG3 encoding nucleic acid comprises an expression vector expressing a BAG3 protein. The teachings of Cao set forth above are directed to use of a BAG3-encoding plasmid, which is an expression vector. As such, the method obvious over the teachings of Cao in view of Sandoval that meets the limitations of claim 2 also meets the limitations of claim 11.
Claim 13 encompasses a method of claim 11 wherein the vector further comprises a plasmid. The teachings of Cao set forth above are directed to use of a BAG3-encoding plasmid. As such, the method obvious over the teachings of Cao in view of Sandoval that meets the limitations of claim 2 also meets those of claim 13.
Claims 21 and 24 encompass a method of claim 11 wherein the vector further comprises a promoter (claim 21) or stop codon (claim 24). The plasmid encoding a BAG3 protein inherently comprises a gene promoter to start transcription and a stop codon to stop translation, or it would not express a functional BAG3 protein. As such, the method obvious over the teachings of Cao in view of Sandoval that meets the limitations of claim 2 also meets the limitations of claims 21 and 24.
Claim 25 encompasses a method of claim 2 wherein the patient is human. Parkinson’s disease is a human disease, and the teachings of Cao set forth above are directed to use of human BAG3 (page 103). As such, the method of treatment of Parkinson’s disease over the teachings of Cao in view of Sandoval that meets the limitations of claim 2 also meets the limitations of claim 25.
Claims 12-16, 21-23 and 28-33 are rejected under 35 U.S.C. 103(a) as being unpatentable over Cao et al (2017. Neurobiology of Aging. 104-115), and further in view of Sandoval (2021. J Parkinson’s Dis. 11(Suppl 2): S189-S197. Pre-press publication date of 6/4/21) as applied to claims 2, 11 or 12, and further in view of Grandinaru et al, U.S. Patent Application Publication 20200165576, published 5/28/20. The earliest date to which the instant application claims priority is 10/22/21.
Claims 13-15 encompass a method of claim 11 wherein the expression vector comprises a viral vector (claim 13) that is an adenovirus-associated virus vector (claim 14) that is any of AAV1-AAV12 (claim 15).
The teachings of Cao and Sandoval are set forth above. Neither Cao or Sandoval teach use of AAV vectors for gene therapy in Parkinson’s Disease.
Gradinaru teaches use AAVs having “increased specificity and efficiency of viral transduction in targeted cell-types, for e.g., the brain” (see Abstract). Gradinaru teaches that the AAVs may contain “a heterologous polynucleotide comprising a nucleotide sequence encoding a gene product” (¶ 10). Gradinaru teaches that AAVs can be any of AAV1-AAV12 (¶ 95).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treatment of Parkinson’s disease comprising administering a BAG3-encoding nucleic acid that is obvious over the teachings of Cao in view of Sandoval, as set forth above for claims 2, 11 and 12, and further modify it to substitute an AAV, including any of AAV1-12, comprising a polynucleotide encoding BAG3 for the plasmid encoding BAG3 taught by Cao. The person of ordinary skill in the art would have been motivated to make such a change in order to take advantage of the improvements in targeting brain cells taught by Gradinaru, and would have had a reasonable expectation of success because Gradinaru teaches use of such vectors generally for use with expression of any heterologous polypeptide of interest. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007). The modified method of treatment obvious over the teachings of Cao in view of Sandoval and further in view of Gradinaru meets the limitations of claims 13-15.
Claims 12, 21 and 22 encompass a method of claim 11 wherein the expression vector further comprises a promoter that is tissue specific (claims 12 and 21) and that confers expression in the central nervous system (claim 22). Gradinaru further teaches that the nucleic acid in the AAV can include a promoter (¶ 169) that further “may provide expression of the therapeutic gene expression product for a period of time in targeted tissues such as, but not limited to, the central nervous system” (¶ 170). As such, it would have further been obvious to use such an embodiment taught by Gradinaru when practicing the modified method obvious over the teachings of Cao in view of Sandoval and further in view of Gradinaru.
Claim 16 encompasses a method of claim 12 wherein the expression vector is a pseudotyped viral vector. Gradinaru further teaches that the AAV can be a pseudotyped AAV (¶ 94). As such, it would have further been obvious to use such an embodiment taught by Gradinaru when practicing the modified method obvious over the teachings of Cao in view of Sandoval and further in view of Gradinaru.
Claim 23 encompasses a method of claim 11 wherein the expression vector further comprises an AAV inverted terminal repeated (ITR). Gradinaru further teaches that the AAV may comprises a nucleic acid sequence flanked by AAV inverted terminal repeat (ITR) sequences (¶ 236). As such, it would have further been obvious to use such an embodiment taught by Gradinaru when practicing the modified method obvious over the teachings of Cao in view of Sandoval and further in view of Gradinaru.
Claims 28-33 each encompass a method of claim 13 wherein the viral vector is administered at a dose in a range from about 3.0 x 1012 vg/kg to 5.0 x 1012 vg/kg. This is the range recited in claim 33, but this range is also encompassed by the ranges recited in each of claims 28-32. Gradinaru further teaches that the AAV can be administered at 3 x 1012 vg/kg, 4 x 1012 vg/kg or 5.0 x 1012 vg/kg (¶ 214), each of which falls within the range recited in each of claims 28-33. As such, it would have further been obvious to use any such dosage taught by Gradinaru when practicing the modified method obvious over the teachings of Cao in view of Sandoval and further in view of Gradinaru.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674