DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of group I, VASH1, nucleotides 1-21 of SEQ ID NO: 18, coding sequences for at least a second VASH-SVBP inhibitor, and AAV vector in the reply filed on 7/29/25 is acknowledged.
Claims 10, 11, and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/29/25.
Nucleotides 1-21 of SEQ ID NOs: 16, 17, and 18 have been examined because these are minimal species within the same target sequence (VASH1).
Improper Markush Rejection
Claims 1, 5, 9, 12-16, and 18 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. Claims 9, 12-16, and 18 are rejected because they depend from claim 1 and do not obviate the rejection. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to any shRNA that comprises a sequence specifically targeted to VASH1, VASH2, or SVBP, which is a genus of shRNAs that each have a different sequence and activity depending upon the sequence of the target. Each target has a different sequence and activity. The claims are directed to an enormous genus of shRNAs that are specifically targeted to different targets.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific shRNA to a separate target is dependent upon the specific sequence of nucleotides of the target. There is no expectation that any one shRNA to any specific target can be substituted for any shRNA with a completely different sequence directed to a completely different target with the expectation of the same activity.
As set forth in MPEP2117, “Note that where a Markush group includes only materials from a recognized scientific class of equivalent materials or from an art-recognized class, "the mere existence of such a group in an application tend[s] to prove the equivalence of its members and when one of them [is] anticipated the group [is] therefore rendered unpatentable, in the absence of some convincing evidence of some degree of non-equivalency of one or more of the remaining members." In re Ruff, 256 F.2d 590, 598-99, 118 USPQ 340, 348 (CCPA 1958)("[A]ctual equivalence is not enough to justify refusal of a patent on one member of a group when another member is in the prior art. The equivalence must be disclosed in the prior art or be obvious within the terms of Section 103." Id. at 599, 118 USPQ at 348).”
In the instant case, art against any one shRNA to a specific target would not be evidence against any of the remaining members that have completely different sequences and do not have identical activity.
Response to Arguments
Contrary to applicant’s assertion, the claims do invoke the improper Markush rejection for the reasons set forth above. Although the claims have been limited to shRNAs, the claims recite three different targets with different sequences and different activities.
Claim Rejections - 35 USC § 112
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 16 and 29 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 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.
Instant claim 29 is directed to a pharmaceutical composition comprising a nucleic acid sequence comprising a non-viral vector which is a lipid particle comprising a nucleic acid molecule comprising a coding sequence for an inhibitor of VASH-SVBP complex operably linked to regulatory sequences which direct expression thereof and a lipid delivery vehicle and/or carrier.
The specification does not adequately describe compositions comprising a nucleic acid sequence comprising a non-viral vector which is a lipid particle comprising a nucleic acid molecule comprising a coding sequence. As claimed, the nucleic acid sequence comprises the non-viral vector and the non-viral vector comprises a nucleic acid.
The claims is directed to an expression cassette comprising a coding sequence for any inhibitor of VASH-SVBP complex. Without further description of the structure required for the function, one would not be able to readily envision which compounds necessarily have the structure to result in the function of inhibiting the VASH-SVBP complex. The claim is not limited to any specific type of inhibitor that has any specific structural relationship to any specific target. The compound in fact can act on any possible target as long as it has the effect of inhibiting the VASH-SVBP complex, which is a genus of compounds that are not adequately described in the specification.
The specification discloses specific shRNAs targeted to VASH1, VASH2, or SVBP. The minimal species are not representative of the entire claimed genus.
Additionally, claim 16 requires for the replication-defective virus to have an AAV capsid from AAV9, AAVhu31, AAVhu32, AAVhu68, or “a variant of any one of these adeno-associated capsids which targets cardiac cells” The specification does not adequately describe variants of any one of AAV9, AAVhu31, AAVhu32, or AAVhu68 that target cardiac cells. The specification does not adequately describe the structure required for this function.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for each of the instantly recited genuses that have the required function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Response to Arguments
The amendments to the claims overcame the rejection except for claims 16 and 29, which applicant did not respond to.
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)(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.
(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.
Claim(s) 1, 3, 12-14, 18, and 29 is/are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by Andrieux et al. (WO 2019/081730 A1).
Andrieux et al. teach methods and pharmaceutical compositions for treating tubulin carboxypeptidases (TCP) associated diseases such as neurological disorders and cardiovascular diseases with an inhibitor of activity or expression of Vasohibinor Vasohibin/SVBP complex (abstract).
Andrieux et al. claims:
1. An inhibitor of Vasohibin or of Vasohibin/SVBP (Small Vasohibin-Binding Protein) complex activity or expression for use in a method for treating a tubulin carboxypeptidases (TCP) associated disease in a subject in need thereof.
2. The inhibitor for use according to claim 1, wherein the tubulin carboxypeptidases associated disease is a neurological disorder.
3. The inhibitor for use according to claim 2, wherein the neurological disorders is a neurodegenerative disorder selected form the group consisting of multiple sclerosis, stroke, amyotrophic lateral sclerosis, Parkinson disease, Huntington disease and Alzheimer's disease
4. The inhibitor for use according to claim 3, wherein the neurodegenerative disorders is Alzheimer disease.
5. The inhibitor for use according to claim 1, wherein the tubulin carboxypeptidases associated disease is a cardiovascular disease selected from the list consisting myocardial infarction, myocardial infarction induced cardiovascular dysfunction, heart failure, cardiomyopathy and dystrophinopathy.
6. The inhibitor for use according to claim 5, wherein the cardiovascular disease is cardiomyopathy.
7. The inhibitor for use according to any one of claim 1 to 6, wherein the inhibitor of Vasohibin activity is a small organic molecule or a biological molecule.
8. The inhibitor for use according to claim 7, wherein the inhibitor of Vasohibin activity is selected from the list consisting of inhibitor of activity of vasohibin- 1 or vasohibin- 2.
9. The inhibitor for use according to any one of claim 1 to 6, wherein the inhibitor of Vasohibin expression or of Vasohibin/SVBP complex expression is selected from the list consisting of antisense oligonucleotides, siRNAs, shRNAs and ribozymes.
10. The inhibitor for use according to claim 9, wherein the inhibitor of Vasohibin/SVBP complex expression is selected from the list consisting of inhibitor of expression of vasohibin-1 vasohibin-2, or SVBP.
11. A pharmaceutical composition for use in a method for treating tubulin carboxypeptidases (TCP) associated disease in a subject in need thereof, comprising the inhibitor of Vasohibin or Vasohibin/SVBP complex activity or expression according to any claim 1 to 10.
12. The pharmaceutical composition for use according to claim 11, wherein the tubulin carboxypeptidases associated diseases is selected from the list consisting of neurological disorder and cardiovascular disease.
Claims 1, 8, and 9 of Andrieux et al. result in a shRNA targeting VASH-SVBP complex, wherein the VASH is VASH-1 (instant claims 1-4).
Andrieux et al. teach that the shRNA of the invention may be delivered in vivo alone or in association with a vector. In its broadest sense, a "vector" is any vehicle capable of facilitating the transfer of the antisense oligonucleotide, siRNA, shRNA or ribozyme nucleic acid to the cells and preferably cells expressing vasohibin/SVBP complex. Preferably, the vector transports the nucleic acid to cells with reduced degradation relative to the extent of degradation that would result in the absence of the vector. In general, the vectors useful in the invention include, but are not limited to, plasmids, phagemids, viruses, other vehicles derived from viral or bacterial sources that have been manipulated by the insertion or incorporation of the shRNA nucleic acid sequences. Viral vectors are a preferred type of vector and include, but are not limited to nucleic acid sequences from the following viruses: retrovirus, such as moloney murine leukemia virus, harvey murine sarcoma virus, murine mammary tumor virus, and rous sarcoma virus; adenovirus, adeno-associated virus; SV40-type viruses; polyoma viruses; Epstein-Barr viruses; papilloma viruses; herpes virus; vaccinia virus; polio virus; and RNA virus such as a retrovirus. One can readily employ other vectors not named but known to the art (pages 15 and 16).
Andrieux et al. teach that retroviruses have been approved for human gene therapy trials. Most useful are those retroviruses that are replication-deficient (i.e., capable of directing synthesis of the desired proteins, but incapable of manufacturing an infectious particle). Such genetically altered retroviral expression vectors have general utility for the high-efficiency transduction of genes in vivo. Standard protocols for producing replication-deficient retroviruses (including the steps of incorporation of exogenous genetic material into a plasmid, transfection of a packaging cell lined with plasmid, production of recombinant retroviruses by the packaging cell line, collection of viral particles from tissue culture media, and infection of the target cells with viral particles) are provided (page 16).
Therefore, Andrieux et al. teach a replication-defective vector (page 16)for use treating patients with heart failure (claim 5 of Andrieux et al.) comprising an expression cassette comprising a coding sequence for an inhibitor of VASH1-SVBP complex operably linked to regulatory sequences to direct the expression thereof (instant claims 1-4). The design and use of replication-defective viruses are known and routine in the art for delivery of shRNAs.
Andrieux et al. teach that preferred viruses for certain applications are the adenoviruses and adeno-associated (AAV) viruses, which are double-stranded DNA viruses that have already been approved for human use in gene therapy (instant claims 13 and 14).
Andrieux et al. teach that the molecules can be generated by in vitro or in vivo transcription of DNA sequences encoding the RNA molecule. Such DNA sequences can be incorporated into a wide variety of vectors that incorporate suitable RNA polymerase promoters such as the T7 or SP6 polymerase promoters.
Andrieux et al. teach that the shRNA nucleic acid sequence is under the control of a heterologous regulatory region, e.g., a heterologous promoter. The promoter may be specific for the monocyte or macrophage (instant claim 12). The promoter meets the instant limitation of being regulatable.
Andrieux et al. teach that vectors are well known in the art and that any vector that causes the production of the shRNA can be utilized, which encompasses viral and non-viral vectors (instant claim 17). Andrieux et al. teach plasmid vectors.
Andrieux et al. teach that the inhibitor of Vasohibin/SVBP complex activity or expression may be combined with pharmaceutically acceptable excipients, and optionally sustained-release matrices, such as biodegradable polymers, to form therapeutic compositions (instant claim 18).
Andrieux et al. teach delivery from a liposome or lipid (instant claim 29).
Therefore, the claims are anticipated by Andrieux et al.
Response to Arguments
Andrieux et al. anticipate each limitation of the instant claims. Contrary to applicant’s argument regarding Andrieux et al. not providing an enabling disclosure, MPEP 2121.01 requires such under the conditions that mere naming or description of the subject matter is insufficient provided that it cannot be produced without undue experimentation, which is not the case in the instant situation. MPEP 2121 states that prior art is presumed to be operable/enabling. When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Although applicant argues the quantity of species taught by the reference, Andrieux et al. anticipate each species taught by Andrieux et al. and was in possession of each.
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.
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 as of the effective filing date of the claimed invention(s) 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 as of the effective filing date of the later invention 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.
Claim(s) 1, 3, 9, 12-16, 18, and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andrieux et al. (WO 2019/081730 A1), in view of Roelvink et al. (EP 2 363 483 A2), and Chatterjee et al. (US 9,890,396 B2).
Andrieux et al. teach methods and pharmaceutical compositions for treating tubulin carboxypeptidases (TCP) associated diseases such as neurological disorders and cardiovascular diseases with an inhibitor of activity or expression of Vasohibinor Vasohibin/SVBP complex (abstract).
Andrieux et al. claims:
1. An inhibitor of Vasohibin or of Vasohibin/SVBP (Small Vasohibin-Binding Protein) complex activity or expression for use in a method for treating a tubulin carboxypeptidases (TCP) associated disease in a subject in need thereof.
2. The inhibitor for use according to claim 1, wherein the tubulin carboxypeptidases associated disease is a neurological disorder.
3. The inhibitor for use according to claim 2, wherein the neurological disorders is a neurodegenerative disorder selected form the group consisting of multiple sclerosis, stroke, amyotrophic lateral sclerosis, Parkinson disease, Huntington disease and Alzheimer's disease
4. The inhibitor for use according to claim 3, wherein the neurodegenerative disorders is Alzheimer disease.
5. The inhibitor for use according to claim 1, wherein the tubulin carboxypeptidases associated disease is a cardiovascular disease selected from the list consisting myocardial infarction, myocardial infarction induced cardiovascular dysfunction, heart failure, cardiomyopathy and dystrophinopathy.
6. The inhibitor for use according to claim 5, wherein the cardiovascular disease is cardiomyopathy.
7. The inhibitor for use according to any one of claim 1 to 6, wherein the inhibitor of Vasohibin activity is a small organic molecule or a biological molecule.
8. The inhibitor for use according to claim 7, wherein the inhibitor of Vasohibin activity is selected from the list consisting of inhibitor of activity of vasohibin- 1 or vasohibin- 2.
9. The inhibitor for use according to any one of claim 1 to 6, wherein the inhibitor of Vasohibin expression or of Vasohibin/SVBP complex expression is selected from the list consisting of antisense oligonucleotides, siRNAs, shRNAs and ribozymes.
10. The inhibitor for use according to claim 9, wherein the inhibitor of Vasohibin/SVBP complex expression is selected from the list consisting of inhibitor of expression of vasohibin-1 vasohibin-2, or SVBP.
11. A pharmaceutical composition for use in a method for treating tubulin carboxypeptidases (TCP) associated disease in a subject in need thereof, comprising the inhibitor of Vasohibin or Vasohibin/SVBP complex activity or expression according to any claim 1 to 10.
12. The pharmaceutical composition for use according to claim 11, wherein the tubulin carboxypeptidases associated diseases is selected from the list consisting of neurological disorder and cardiovascular disease.
Claims 1, 8, and 9 of Andrieux et al. result in a shRNA targeting VASH-SVBP complex, wherein the VASH is VASH-1 (instant claims 1-4).
Andrieux et al. teach that the shRNA of the invention may be delivered in vivo alone or in association with a vector. In its broadest sense, a "vector" is any vehicle capable of facilitating the transfer of the antisense oligonucleotide, siRNA, shRNA or ribozyme nucleic acid to the cells and preferably cells expressing vasohibin/SVBP complex. Preferably, the vector transports the nucleic acid to cells with reduced degradation relative to the extent of degradation that would result in the absence of the vector. In general, the vectors useful in the invention include, but are not limited to, plasmids, phagemids, viruses, other vehicles derived from viral or bacterial sources that have been manipulated by the insertion or incorporation of the shRNA nucleic acid sequences. Viral vectors are a preferred type of vector and include, but are not limited to nucleic acid sequences from the following viruses: retrovirus, such as moloney murine leukemia virus, harvey murine sarcoma virus, murine mammary tumor virus, and rous sarcoma virus; adenovirus, adeno-associated virus; SV40-type viruses; polyoma viruses; Epstein-Barr viruses; papilloma viruses; herpes virus; vaccinia virus; polio virus; and RNA virus such as a retrovirus. One can readily employ other vectors not named but known to the art (pages 15 and 16).
Andrieux et al. teach that retroviruses have been approved for human gene therapy trials. Most useful are those retroviruses that are replication-deficient (i.e., capable of directing synthesis of the desired proteins, but incapable of manufacturing an infectious particle). Such genetically altered retroviral expression vectors have general utility for the high-efficiency transduction of genes in vivo. Standard protocols for producing replication-deficient retroviruses (including the steps of incorporation of exogenous genetic material into a plasmid, transfection of a packaging cell lined with plasmid, production of recombinant retroviruses by the packaging cell line, collection of viral particles from tissue culture media, and infection of the target cells with viral particles) are provided (page 16).
Therefore, Andrieux et al. teach a replication-defective vector (page 16)for use treating patients with heart failure (claim 5 of Andrieux et al.) comprising an expression cassette comprising a coding sequence for an inhibitor of VASH1-SVBP complex operably linked to regulatory sequences to direct the expression thereof (instant claims 1-4). The design and use of replication-defective viruses are known and routine in the art for delivery of shRNAs.
Andrieux et al. teach that preferred viruses for certain applications are the adenoviruses and adeno-associated (AAV) viruses, which are double-stranded DNA viruses that have already been approved for human use in gene therapy (instant claims 13 and 14).
Andrieux et al. teach that the molecules can be generated by in vitro or in vivo transcription of DNA sequences encoding the RNA molecule. Such DNA sequences can be incorporated into a wide variety of vectors that incorporate suitable RNA polymerase promoters such as the T7 or SP6 polymerase promoters.
Andrieux et al. teach that the shRNA nucleic acid sequence is under the control of a heterologous regulatory region, e.g., a heterologous promoter. The promoter may be specific for the monocyte or macrophage (instant claim 12). The promoter meets the instant limitation of being regulatable.
Andrieux et al. teach that vectors are well known in the art and that any vector that causes the production of the shRNA can be utilized, which encompasses viral and non-viral vectors (instant claim 17). Andrieux et al. teach plasmid vectors.
Andrieux et al. teach that the inhibitor of Vasohibin/SVBP complex activity or expression may be combined with pharmaceutically acceptable excipients, and optionally sustained-release matrices, such as biodegradable polymers, to form therapeutic compositions (instant claim 18).
Andrieux et al. teach delivery from a liposome or lipid (instant claim 29).
Although Andrieux et al. does not teach that the vector has coding sequences for a second inhibitor, it was routine in the art to deliver sequences to express more than one inhibitory compound in the same vector.
For example, Roelvinc et al. teach multiple promoter expression cassettes for simultaneous delivery of RNAi agents (title, abstract) (instant claim 9). Roelvinc et al. teach expression cassettes with sequences to express more than one siRNA ([0014], [0031]). Roelvinc et al. teach that the vector is an AAV vector. One would reasonably expect success of delivering multiple shRNAs of Andrieux et al. via incorporation of coding sequences for another inhibitor with the motivation of each having inhibitory effect on the target.
Andrieux et al. does not teach that the AAV has an adeno-associated virus capsid from clade F or AAV9 (instant claims 15 and 16). However, incorporation of these elements would have been a matter of design choice because AAV Clade F vectors were known to deliver shRNAs, as evidenced by Chatterjee et al. (column 47).
Additionally, Chatteree et al. teach that the AAV capsid is the capsid of a Clade F AAV selected from the group consisting of AAV9, AAVF1, AAVF2, AAVF3, AAVF4, AAVF5, AAVF6, AAVF7, AAVF8, AAVF9, AAVF11, AAVF12, AAVF13, AAVF14, AAVF15, AAVF16, AAVF17, AAVHU31, and AAVHU32 (column 10).
Response to Arguments
Applicant argus that one would not have combined the references but does not offer a clear reasoning why this is the case. Roelvinc et al is evidence that it was routine in the art to deliver sequences to express more than one inhibitory compound in the same vector; and Chatteree teaches species of AAV capsids that were known to be utilized to deliver shRNAs.
Allowable Subject Matter
Claims 6 and 8 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 30-32 are allowed.
Conclusion
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 Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636