DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 18-24, 26-34, and 38-40, of record 3/19/2026, are pending and subject to prosecution. Claim 18 is amended. Claim 40 is newly added.
Status of Prior Rejections/Response to Arguments
RE: Objection to the specification:
The submission of a substitute specification is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claim 1 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Bandman et al. (US 5972684A):
The applicant asserts that Bandman et al. fail to disclose treating pain, as pain and inflammation “are distinct physiological conditions with different underlying mechanisms” (Applicant Remarks, page 5).
The applicant’s argument is not found persuasive. Because pain is considered a cardinal feature of inflammation (See Ji et al., Abstract and page 572, col. 1, 1; Botting et al., Abstract and page 2, col. 2, full 1-2), the prevention or treatment of inflammation, as disclosed by Bandman et al. (See col. 3, line 33-37), would therefore read on the prevention or treatment of pain, as well.
The rejection is maintained.
RE: Rejection of claims 18-20, 25-26, 28-29, and 32-33 under 35 U.S.C. 103 over Bandman et al. (US 5972684A) in view of Skaggs et al. (Gene, 1993) and Sjöblom et al. (FEBS Letters, 1996):
RE: Rejection of claims 18-21, 23-30, 32-33, and 38 under 35 U.S.C. 103 over Bandman et al. (US 5972684A), of record, in view of Skaggs et al. (Gene, 1993) and Sjöblom et al. (FEBS Letters, 1996), further in view of Zhuang et al. (PLoS One, 2015), as evidenced by Agilent Technologies (AAV Helper-Free System instruction manual, 2015):
RE: Rejection of claims 18-20, 22, 25-26, 28-29, and 32-33 under 35 U.S.C. 103 over Bandman et al. (US 5972684A) in view of Skaggs et al. (Gene, 1993) and Sjöblom et al. (FEBS Letters, 1996), further in view of Mata et al. (Physiology & Behavior, 2002):
RE: Rejection of claims 18-20, 25-26, 28-29, and 32-34 under 35 U.S.C. 103 over Bandman et al. (US 5972684A) in view of Skaggs et al. (Gene, 1993) and Sjöblom et al. (FEBS Letters, 1996), further in view of Weber-Adrian et al. (Gene Therapy, 2015):
RE: Rejection of claims 18-20, 25-26, 28-29, 32-33, and 38 under 35 U.S.C. 103 over Bandman et al. (US 5972684A) in view of Skaggs et al. (Gene, 1993) and Sjöblom et al. (FEBS Letters, 1996), further in view of Gorman (US 20080019975 A1):
The applicant asserts that Bandman et al. teach a sequence encoding CA11 rather than CA8 and therefore do not provide a basis for substitution of a CA8 sequence or motivation to do so (Applicant Remarks, page 6-8). The applicant also asserts that the position of the Office is inconsistent with respect to the teachings of Bandman et al. (Applicant Remarks, page 8-9).
The applicant’s arguments are not found persuasive. Prior art is relevant for all that it contains and would have reasonably suggested to one of ordinary skill in the art. See MPEP 2123(I). Given the entirety of the teachings of Bandman et al., the position of the Office is not inconsistent. While Bandman et al. teach a sequence that corresponds to carbonic anhydrase 11 rather than carbonic anhydrase 8, they also teach that carbonic anhydrase expression is closely associated with inflammation and suggest a role for “CAVIII” in inflammation and other disorders on the basis of chemical and structural homology between or among carbonic anhydrase isoforms (See col. 19, line 6-11). On this basis of general similarity in structure and function among the carbonic anhydrases, as disclosed by Bandman et al., one of ordinary skill would find it reasonable to substitute another isoform, such as CAVIII, for “CAVIII” in the method of Bandman et al. Additionally, the teaching that “[w]here CA decreases inflammation, it is beneficial to provide the protein or increase the expression of CAVIII” (See col. 19, line 15-17) further implies that carbonic anhydrases could be applied interchangeably as anti-inflammatory agents.
The rejections are maintained in modified form to address amended limitations.
New/Maintained Objections/Rejections
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 1 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bandman et al. (US 5972684A), of record.
Regarding claim 1: Bandman et al. teach the administration of carbonic anhydrase 8 for treating or preventing inflammation (which reads on “treating or preventing pain”) in a subject (See col. 4, line 35-38). Bandman et al. also teach an expression vector encoding an amino acid sequence identical to instant SEQ ID NO 11 but misidentified as carbonic anhydrase 8 (See col. 3, line 40-43; col. 4, line 10-13; SEQ ID NO 1; and alignment below). While Bandman et al. do not expressly teach the sequence of SEQ ID NO 1 as carbonic anhydrase 11, use of a vector comprising the sequence, as intended by Bandman et al. for treating inflammation, would anticipate the claimed invention.
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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.
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.
Claims 18-20, 25-26, 28-29, 32-33, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Bandman et al. (US 5972684A), of record, in view of Skaggs et al. (Gene, 1993), of record, and Sjöblom et al. (FEBS Letters, 1996), of record.
The teachings of Bandman et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 18-20, 25-26, 29, 32-33, and 40: Bandman et al. teach administration of a vector capable of expressing a carbonic anhydrase or a fragment thereof to a subject to treat inflammation (which reads on “treating or preventing pain in a subject in need thereof”) (See col. 19, lines 40-44). Bandman et al. teach that carbonic anhydrase expression is closely associated with inflammation and suggest a role for “CAVIII” in inflammation and other disorders on the basis of chemical and structural homology between or among carbonic anhydrase isoforms (See col. 19, line 6-11). The subject treated with a carbonic anhydrase can be human (See col. 24, lines 23-26). The vector can be viral, such as adenovirus, retrovirus, herpesvirus, or vaccinia virus (See col. 16, lines 11-15 and col. 22, lines 63-66). Carbonic anhydrase or a fragment thereof can be administered for preventing or relieving inflammation (which reads on “inflammatory pain”) associated with complications of cancer (which reads on “wherein the pain is caused by cancer”) (See col. 19, lines 18-44). The expression vector can be administered by oral, intravenous (which reads on “via catheter” and “via needle”), and intramuscular (which reads on “via needle”) routes (See col. 24, lines 40-45). Bandman et al. also teach that it is beneficial to provide the protein or increase expression of “CAVIII” where carbonic anhydrase decreases inflammation (which reads on “to a site where pain arises”) (See col. 19, lines 15-17). Bandman et al. do not teach a carbonic anhydrase having the sequence of GenBank Accession No. NP_001308766.1.
Skaggs et al. teach the amino acid sequence of human carbonic anhydrase-related protein (CARP), which is identical to the sequence of NP_001308766.1 (See fig. 1 and alignment below) and which comprises a sequence identical to the sequence of instant SEQ ID NO 30 (See underlined portion of alignment below).
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Sjöblom et al. teach that the CARP taught by Skaggs et al. is also known as CAVIII (See page 322, col. 1, ¶2).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Bandman et al. to substitute the CARP sequence taught by Skaggs et al. comprising CAVIII, which Sjöblom et al. teach is the same protein as CARP. Substitution of one known element for another known element is considered to be prima facie obvious, absent evidence that the result of the substitution yields more than predictable results.
Regarding claim 28: Following the discussion of claims 18-20, 25-26, 29, 32-33, and 40, Bandman et al. teach that the expression vector can be administered by injection and for treating inflammation associated with disorders such as osteoarthritis and rheumatoid arthritis but fail to teach intra-articular administration of the expression vector (See col. 19, lines 18-39 and col. 25, lines 31-35). However, one having skill in the art would have recognized that injection of the vector into joints would have been obvious to try based on the teachings of Bandman et al. for the treatment or prevention of joint pain.
Claims 18-21, 23-30, 32-33, and 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Bandman et al. (US 5972684A), of record, in view of Skaggs et al. (Gene, 1993), of record, and Sjöblom et al. (FEBS Letters, 1996), of record, further in view of Zhuang et al. (PLoS One, 2015), of record, as evidenced by Agilent Technologies (AAV Helper-Free System instruction manual, 2015), of record.
The teachings of Bandman et al., Skaggs et al., and Sjöblom et al., are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claims 21 and 23: Following the discussion of claims 18-20, 25-26, 28-29, 32-33, and 40, Bandman et al., modified by Skaggs et al. and Sjöblom et al., render obvious the administration of a CAVIII expression vector for treating pain but do not teach the vector as AAV or as comprising a CMV promoter.
Zhuang et al. teach the use of the pAAV-MCS expression vector for administering murine carbonic anhydrase 8 (See page 4, ¶2). Agilent Technologies teach the pAAV-MCS expression vector contains the CMV promoter (See page 9, ¶1). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Bandman et al., modified by Skaggs et al. and Sjöblom et al., to comprise the use of a pAAV-MCS vector, as taught by Zhuang et al., for administering CAVIII to a subject. One would be motivated to make this modification because Zhuang et al. teach this vector as appropriate for expression of carbonic anhydrase 8 (See fig. 5-6). There would be a reasonable expectation of success in doing so because Zhuang et al. demonstrate that carbonic anhydrase 8 can be expressed from such a vector for therapeutic treatment.
Regarding claims 24 and 39: Following the discussion of claims 18-20, 25-26, 28-29, 32-33, and 40, Bandman et al., modified by Skaggs et al. and Sjöblom et al., render obvious the administration of an expression vector CAVIII for preventing or treating inflammation but do not teach its use for neuropathic pain or nociceptive pain.
Zhuang et al. teach that a CAVIII expression vector can be directly injected into a nerve for decreasing sensitivity to pain (See page 15, ¶1-2; page 16, ¶1; and page 17, ¶1). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to have modified the methods of Bandman et al., modified by Skaggs et al. and Sjöblom et al., for treating neuropathic pain. Zhuang et al. demonstrate that direct injection of the vector into a nerve can prevent or limit nociceptive pain (See fig. 7), suggesting that the approach can be applied to neuropathic pain, as well. There would have been a reasonable expectation of success in doing so because the expression vectors of Bandman et al., modified by Skaggs et al. and Sjöblom et al., could readily be injected into nerves and because Zhuang et al. had demonstrated the efficacy of injecting carbonic anhydrase 8 expression vectors into nerves.
Regarding claims 27 and 30: Following the discussion of claims 18-20, 25-26, 28-29, 32-33, and 40, Bandman et al., modified by Skaggs et al. and Sjöblom et al., render obvious the administration of an expression vector encoding CAVIII for preventing or treating inflammation but do not teach administration of the vector to the dorsal root ganglion or trigeminal ganglia.
Zhuang et al. teach that CAVIII expression vectors can be administered by injection into nerves (See page 15, ¶1-2; page 16, ¶1; and page 17, ¶1).
It would have been obvious to one skilled in the at prior to the effective filing date of the claimed invention to modify the methods of Bandman et al., modified by Skaggs et al. and Sjöblom et al., with the teachings of Zhuang et al. for the administration of CAVIII expression vector directly into nerves. While Zhuang et al. teach injection into the sciatic nerve, not the dorsal root ganglion or trigeminal ganglia, one skilled in the art would recognize that the injection step could be applied to other nerve fibers or nerve cell bodies. There would have been a reasonable expectation of success in doing so because Zhuang et al. demonstrate decreased pain sensitivity and inflammation in mice that had received sciatic nerve injections of a carbonic anhydrase 8 expression vector and because Zhuang et al. demonstrate that sciatic nerve injections result in expression of the vector within the dorsal root ganglion and spinal cord, suggesting that direct injection to these or other nerve sites would be feasible (See fig. S3-S5). Additionally, Bandman et al. teach that neurotropic expression vectors such as herpesviruses can be used for expression of carbonic anhydrase (See col. 22, lines 63-66).
Claims 18-20, 22, 25-26, 28-29, 32-33, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Bandman et al. (US 5972684A), of record, in view of Skaggs et al. (Gene, 1993), of record, and Sjöblom et al. (FEBS Letters, 1996), of record, further in view of Mata et al. (Physiology & Behavior, 2002), of record.
The teachings of Bandman et al., Skaggs et al., and Sjöblom et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 22: Following the discussion of claims 18-20, 25-26, 28-29, 32-33, and 40, Bandman et al., modified by Skaggs et al. and Sjöblom et al., render obvious the administration of a viral CAVIII expression vector but do not expressly teach the vector as a herpes simplex virus.
Mata et al. teach that a herpes simplex virus vector can be used in gene delivery to nerves for treating pain in mice (See page 485, col. 1, ¶2).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Bandman et al., modified by Skaggs et al. and Sjöblom et al., to use a herpes simplex virus, such as is taught by Mata et al., for administration of CAVIII. One would be motivated to make this modification in order to target delivery of the CAVIII gene to neurons. There would be a reasonable expectation of success in doing so because Bandman et al. teach that carbonic anhydrase can be expressed from a herpesvirus.
Claims 18-20, 25-26, 28-29, 32-34, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Bandman et al. (US 5972684A), of record, in view of Skaggs et al. (Gene, 1993), of record, and Sjöblom et al. (FEBS Letters, 1996), of record, further in view of Weber-Adrian et al. (Gene Therapy, 2015), of record.
The teachings of Bandman et al., Skaggs et al., and Sjöblom et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 34: Following the discussion of claims 18-20, 25-26, 28-29, 32-33, and 40, Bandman et al., modified by Skaggs et al. and Sjöblom et al., render obvious the administration of an expression vector encoding CAVIII by injection but do not teach the use of imaging to administer the vector.
Weber-Adrian et al. teach the use of magnetic resonance imaging-guided focused ultrasound for injecting a viral expression vector into the spinal cord (See fig. 1-2). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to have modified the methods of Bandman et al., modified by Skaggs et al. and Sjöblom et al., with image-guided injection, such as is taught by Weber-Adrian et al., for more accurate delivery of the vector into inflamed tissues. There would have been a reasonable expectation of success in doing so because magnetic resonance imaging-guided ultrasound could be readily used with the administration methods of Bandman et al. and because Weber-Adrian et al. demonstrate robust transgene expression in targeted tissue through guided injection (See fig. 2-4).
Claims 18-20, 25-26, 28-29, 32-33, 38 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Bandman et al. (US 5972684A), of record, in view of Skaggs et al. (Gene, 1993), of record, and Sjöblom et al. (FEBS Letters, 1996), of record, further in view of Gorman (US 20080019975 A1), of record.
The teachings of Bandman et al., Skaggs et al., and Sjöblom et al. are set forth in the rejections above and are incorporated herein in their entirety.
Regarding claim 38: Following the discussion of claims 18-20, 25-26, 28-29, 32-33, and 40, Bandman et al., modified by Skaggs et al. and Sjöblom et al., render obvious the administration of an expression vector encoding CAVIII by injection but do not teach epidural administration.
Gorman teaches administration of TNF-I or NFκB-I inhibitors for treating spinal pain and inflammation (See ¶0017-0019). The inhibitor can be injected in the form of an expression vector (See ¶0196). Administration can be performed epidurally (See ¶0023). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Bandman et al., modified by Skaggs et al. and Sjöblom et al., to include epidural injection, as taught by Gorman, for treating pain. One would be motivated to make this modification for localized relief of pain and/or inflammation. There would be a reasonable expectation of success in doing so because the expression vector of Bandman et al., modified by Skaggs et al. and Sjöblom et al., could be readily injected via epidural routes.
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 JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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