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 .
The amendment filed on 03/25/2026 has been entered.
Amended claims 1-19, 21 and new claims 23-24 are pending in the present application, and they are examined on the merits herein.
Priority
The present application is a CIP of US application with the Serial Number 17/092,779, filed on 11/09/2020, now abandoned; which is a CON of PCT/US20/25705, filed on 03/30/2020; which claims benefit of the provisional application 62/826,676, filed on 03/29/2019.
Upon review of the specifications of the above US applications and the provisional application, it is determined that examined claims are only entitled to the filing date of 04/13/2023. This is because there is no written support in any of the above U.S. applications and provisional application for a method for preventing or treating chronic back pain, including discogenic back pain, in a subject in need thereof.
Response to Amendment
1. The rejection under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for Scope of Enablement was withdrawn in light of currently amended independent claim 1, particularly with the deletion of the limitation “preventing” from the preamble of the claim.
2. The provisional nonstatutory double patenting rejection as being unpatentable over claims 1-7 of copending Application No. 18/900,011 (reference application) in view of Noh et al (WO 2009/117740; IDS), Freemont (Rheumatology 48:5-10; 2009), Ra et al (US 2010/0196329) and Strbo et al (WO 2018/071405) was withdrawn in light of currently amended independent claim 1, particularly with the limitation “wherein the first mammalian cell is one or more selected from the group consisting of a human embryonic kidney cell and an epithelial cell”.
3. The provisional nonstatutory double patenting rejection as being unpatentable over claims 1-7 of copending Application No. 18/900,083 (reference application) in view of Noh et al (WO 2009/117740; IDS), Freemont (Rheumatology 48:5-10; 2009), Ra et al (US 2010/0196329) and Strbo et al (WO 2018/071405) was withdrawn because the co-pending application was abandoned.
Claim Rejections - 35 USC § 103
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.
Amended claims 1-18, 21 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Noh et al (WO 2009/117740; IDS) in view of Freemont (Rheumatology 48:5-10; 2009), Harpstead (US 6,479,066; IDS), Thomas et al (J. Pharm. Toxicologic. Methods 51:187-200, 2005; IDS), Masuda et al (The Spine Journal 4:3308-3408, 2004; IDS) and Strbo et al (WO 2018/071405). This is a modified rejection necessitated by Applicant’s amendment.
The instant claims encompass a method for treating chronic back pain in a subject in need thereof, comprising administering an effective amount of a composition comprising a mixed cell population to an intervertebral disc site of the subject, wherein the mixed cell population comprises a first mammalian cell comprising an exogenous nucleotide sequence encoding a protein having an intervertebral disc regenerating function (e.g., a member of the TGF-beta superfamily such as TGF-beta1) and a second mammalian cell that does not comprise the exogenous nucleotide sequence and is a connective tissue cell (e.g., a chondrocyte), wherein the first mammalian cell is one or more selected from the group consisting of a human embryonic kidney cell and an epithelial cell, and wherein the administration reduces discogenic back pain in the subject, reduces a backpain-associated behavior, and/or reduces sensitivity of the subject to the discogenic back pain.
Noh et al already disclosed at least a method for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site (e.g., torn or herniated) of a mammal, the method comprises: a) inserting a gene encoding a protein having intervertebral disc regenerating function (e.g., a member of TGF-beta superfamily such as TGF-beta1, BMP-2, BMP-3, BMP-4, BMP-7/OP-1 and others) into a first mammalian connective tissue cell, and b) transplanting a mixture of the mammalian connective tissue cell of a) and unmodified second mammalian connective tissue cell into the intervertebral disc defect site via injection; preferably the method does not use a scaffolding or any supporting structure for the cells; wherein the first and second mammalian connective tissue cell may be chondrocyte (e.g., non-disc chondrocyte, juvenile chondrocyte, and specifically the chondrocyte for the second mammalian connective tissue cell is a primed chondrocyte) or fibroblast; and either or both the first and second connective tissue cell may be autologous or allogeneic relative to the mammalian subject or to each other (paragraphs [0002], [0005], [0007], [0035]-[0036], [0043], [0047], [0052] and [00102]; Examples I and IV). Noh et al also taught that the ratio of cells that have not been transfected or transduced with a gene encoding a member of the transforming growth factor beta superfamily to cells that have been transfected or transduced with a TGF superfamily gene may be in the range of about 3-20 to 1, 3-10 to 1 or about 10 to 1 (paragraph [0028]). Noah et al also stated “ When these fibroblastic chondrocytes are incubated or “primed” with a cytokine such as a protein from the TGF-beta superfamily, the cells regain their chondrocytic characteristics, which include production of collagen” (paragraph [0046]); “An advantage of using primed cells in retardation of intervertebral disc degeneration is the ease of creating usable chondrocytes for introduction into the intervertebral disc for production of collagen and otherwise maintenance of the cartilaginous matrix” (paragraph [0047]); and “Alternatively, the cells may be incubated with the cytokine of interest for a time and the combination may be administered to the site of defect without separating out the cytokine” (paragraph [0050]). Noh et al further disclosed that a compound for parenteral administration to a patient in a therapeutically or prophylactically effective amount that includes a TGF-beta superfamily protein and a suitable pharmaceutically acceptable carrier (paragraphs [0058]-[0059]). Noh et al also taught that the connective tissue cell may be stored frozen in 10% DMSO in liquid nitrogen (paragraph [0063]), or in an exemplary cryopreservative media of DMEM, FBS and DMSO in a 5:4:1 ratio (last sentence of paragraph [00117]). In Example IV. 1, Noh et al taught the use of X-ray radiograph to obtain a disc height index of the intervertebral disc to measure its morphology, its level of degeneration or regeneration (paragraphs [0008], [00102]; and Fig. 1D-F); as well as the use of MRI (magnetic resonance image) radiograph to show healing, the slowing, retardation or prevention of degeneration of injured disc (paragraphs [0008], [[0093], 00102]; and Fig. 1A-C). An exemplified dose of a cell mixture comprising TGF-β1-producing chondrocytes and primary untransduced human chondrocytes is about 5 x 106 cells (Table 1 at page 24).
Noah et al did not teach explicitly to treat a subject with a chronic back pain, including a discogenic back pain, using an effective amount of a mixed cell population comprising at least human embryonic kidney cells comprising an exogenous nucleotide sequence encoding a protein having an intervertebral disc regenerating function (e.g., TGF-β1 protein) and chondrocytes that do not comprise the exogenous nucleotide sequence; and the human embryonic kidney cell is irradiated.
Before the filing date of the present application (04/13/2023), Freemont taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain (Abstract). Freemont stated “Studies examining the problem from different directions (e.g. examination of volunteers [4] and patients [5], imaging investigations [6], trials of intervention [7]) have produced evidence implicating the intervertebral disc (IVD) in a significant proportion (at least 40%) of cases of chronic back pain, leading to the use of the term “discogenic back pain”. From the work that has been carried out to date two processes stand out as being important in the origins of discogenic back pain, disc degeneration and nociceptive nerve ingrowth into the normally aneural IVD” (page 5, left column, second and third paragraphs in the “Introduction” section). Freemont also stated “Overall, current data indicate that normal IVD matrix prevents nerve ingrowth into the IVD, but that in degeneration changes in the structure of aggrecan, coupled with altered IVD cell biology lead to nerve ingrowth into pain level IVD and that this is enhanced by the production of neurogenic cytokines during neovascularization of the degenerate IVD” (page 8, left column, last paragraph).
Additionally, Harpstead already taught using human epithelial cells (HeLa), human embryonic kidney cells (HEK), Chinese hamster ovary cells (COS) and other known cell lines derived from tumors or from stem cells that have been developed to divide indefinitely, which provide an unlimited source standardized, genetically homogenous cells in a device to be implanted at a site (e.g., intraperitoneal fat sites, subcutaneous sites, intervertebral discs) in a patient in need thereof (see at least col. 5, line 65 continues to line 65 on col. 7; and issued claims 1, 20-21). Harpstead also disclosed that the implanted cells are capable of producing a therapeutic substance (e.g., BMP, NGF and others) that has a beneficial effect on the host, and that the implanted cells can be genetically engineered transformed cells (col. 6, line 28 continues to line 26 of col. 7).
Thomas et al also disclosed that HEK293 cell line is of epithelial origin and it has been extensively used as an expression tool for recombinant proteins; and some of the principal attributes which have made the HEK cell a popular choice include: (i) quick and easy reproduction and maintenance, (ii) amenability to transfection using a wide variety of methods, (iii) high efficiency of transfection and protein production, and (iv) faithful translation and processing of proteins (see at least the Abstract).
Moreover, Masuda et al already reviewed the prior art literature and reported that growth factors such as TGF-beta1, BMP-2, OP-1/BMP-7 in the form of a recombinant protein and/or a recombinant expression vector increased proteoglycan and/or collagen synthesis, and/or increased cell proliferation in intervertebral disc cells in numerous cell and organ culture systems and in vivo models (see at least the Abstract; and particularly Tables 1-2 and section titled “The gene transfer approach using growth factors” on page 3368). Masuda et al concluded “From the data reviewed above, the application of growth factors, either by direct injection of the protein into the NP or the AF or by the transplantation of IVD cells transfected with therapeutic genes by viral or nonviral gene therapy, is clearly possible as an effective therapeutic approach in the treatment of IVD degeneration” (page 3388, left column, top of first full paragraph).
Furthermore, Strbo et al already taught the use of HEK293 cells that are transfected with the gp96-Ig-ZIKV antigen expression vector for the treatment of a flavivirus infection in a subject, wherein the transfected HEK293 cells were first irradiated (12,000 rads), then suspended in freezing medium comprising 10% DMSO, and 25% human serum albumin prior to subcutaneous administration to a patient (see at least Abstract; particularly paragraphs [0037]-[0039]).
Accordingly, it would have been obvious for an ordinary skilled artisan to modify the teachings of Noh et al by also at least treating a subject with a chronic back pain, including discogenic back pain; selecting and using human embryonic kidney cells such as HEK-293 cells that are inserted/transfected with a gene encoding a protein having intervertebral disc regenerating function such as a member of TGF-beta superfamily (e.g., TGF-beta 1, BMP) to be transplanted in a mixture with unmodified chondrocytes to induce/enhance cartilage, proteoglycans synthesis and/or cell proliferation of endogenous intervertebral disc cells and/or increased cartilage and proteoglycan production provided by the co-implanted unmodified chondrocytes at an intervertebral disc defect site in the subject; as well as irradiating the human embryonic kidney cells comprising an exogenous nucleotide sequence encoding a protein having an intervertebral disc regenerating function in a mixed cell population prior to administering the mixed cell population to the subject; in light of the teachings of Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modifications because: (a) Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain; (b) Harpstead already taught successfully using human epithelial cells (HeLa), human embryonic kidney cells (HEK) which provide an unlimited source of standardized, genetically homogenous cells, including transformed/genetically modified cells, that produce a therapeutic substance in a device to be implanted (e.g., at intervertebral site) in a patient in need thereof; (c) Thomas et al also taught that HEK293 cell line is of epithelial origin and it has many positive attributes that include: (i) quick and easy reproduction and maintenance, (ii) amenability to transfection using a wide variety of methods, (iii) high efficiency of transfection and protein production, and (iv) faithful translation and processing of proteins; (d) Masuda et al already reviewed the prior art literature and reported that growth factors such as TGF-beta1, BMP-2, OP-1/BMP-7 in the form of a recombinant protein and/or a recombinant expression vector increased proteoglycan and/or collagen synthesis, and/or increased cell proliferation in intervertebral disc cells in numerous cell and organ culture systems and in vivo models; and (e) Strbo et al already taught successfully the use of irradiated HEK293 cells that were transfected with the gp96-Ig-ZIKV antigen expression vector for the treatment of a flavivirus infection in a subject.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al; coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified treatment method resulting from the combined teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al as set forth above is indistinguishable and encompassed by the presently claimed invention. Since the modified treatment method has the same method steps and starting materials as those of the presently claimed invention, particularly the treatment method of Noh et al is already useful for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site in a mammal, such modified treatment method would naturally result at least in the reduction of discogenic back pain in the subject, reduction of a back pain-associated behavior, reduction in the sensitivity of the subject to the discogenic back pain, and/or reduction of TrpV1 or TrpA1-dependent calcium influx.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Noh et al (WO 2009/117740; IDS) in view of Freemont (Rheumatology 48:5-10; 2009), Harpstead (US 6,479,066; IDS), Thomas et al (J. Pharm. Toxicologic. Methods 51:187-200, 2005; IDS), Masuda et al (The Spine Journal 4:3308-3408, 2004; IDS) and Strbo et al (WO 2018/071405) as applied to claims 1-3, 12-18 and 20-22 above, and further in view of Ra et al (US 2010/0196329).
The combined teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al were presented above. However, none of the cited references teach specifically using a pharmaceutical carrier comprising about 10 to 20% w/w DMSO and about 1 to 5% w/w saccharose (sucrose).
Before the filing date of the present application (04/13/2023), Ra et al already disclosed at least a cell therapeutic composition comprising adipose-tissue derived mesenchymal stem cells and sucrose as an excipient, and wherein the composition further additionally comprising DMSO as the excipient (Abstract; Summary of the Invention; particularly paragraphs [0010]-[0014]). Ra et al stated “[w]hen the inventive cell therapeutic compositions containing adipose tissue-derived stem cells were stored under frozen storage conditions, the composition containing physiological saline, sucrose, albumin and cryopreservative DMSO showed the highest cell viability upon thawing, and it was observed that the addition of albumin and sugar components to the cell therapeutic composition protected the cells during the freezing and thawing of the cell to improve the viability of the cells” (paragraph [0048]). Ra et al demonstrated that the cell viability in frozen storage conditions was further increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin and 10% DMSO (Example 7, particularly paragraph [0065] and Table 3).
Accordingly, it would have been obvious for an ordinary skilled artisan to further modify the combined teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al by also using a frozen storage medium comprising about 10 % (w/w) DMSO and about 2% saccharose/sucrose (w/w) as a pharmaceutical carrier for the mixed cell population, in light of the teachings of Ra et al as presented above.
An ordinary skilled artisan would have been further motivated to carry out the above modification because Ra et al already demonstrated that the cell viability for a stem cell therapeutic composition in frozen storage conditions was increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin, and 10% DMSO. Moreover, please note that Strbo et al already taught successfully the use of irradiated HEK293 cells that were transfected with the gp96-Ig-ZIKV antigen expression vector in a freezing medium comprising 10% DMSO and 25% human serum albumin for subcutaneous administration into a patient in need of a flavivirus infection treatment.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al, Strbo et al and Ra et al; coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified treatment method resulting from the combined teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al, Strbo et al and Ra et al as set forth above is indistinguishable and encompassed by the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments related to the above modified 103 rejection in the Amendment filed on 03/25/2026 (pages 8-13) have been fully considered, but they are respectfully not found persuasive for the reasons discussed below.
Applicant argued that Noh does not disclose the composition set forth in currently amended claim 1, particularly Noh does not teach or suggest using a HEK cell as the first mammalian cell. Applicant also argued that the combination of asserted references also fails to render the claimed method obvious, particularly the combination of up to six disparate references; and this reconstitution constitutes improper hindsight. Specially, Applicant argued that Thomas is directed to using HEK293 cell line as a vehicle for recombinant protein expression; Harpstead relates generally to a device for implanting mammalian cells; Masuda does not teach engineering a continuous, exogenous HEK-based cellular delivery system for TGF-β1 protein to be co-administered with chondrocytes; Strbo is directed toward the development of infectious disease vaccines where cells are irradiated to create a safe, non-replicating immune target, which is a distinct field from orthopedic structural repair and pain management; and Ra is cited for a composition comprising adipose-tissue derived mesenchymal stem cells containing physiological saline, sucrose, albumin and cryopreservative DMSO. Applicant also argued that the combination of the asserted references failed to teach the claimed functional clinical outcome. Applicant further argued that the mammal intervertebral disc is an exceptionally hostile microenvironment (e.g., avascular, hypoxic, nutrient-derived and subject to immense continuous biomechanical loading); and there is no teaching in the asserted art that would lead an artisan to expect that an irradiated HEK cell (typically utilized in short-lived vaccine presentation of Strbo) would survive, stably express a therapeutic level of TGF-beta, and successfully act synergistically with a co-administered chondrocyte to clinically reduce pain sensitivity in the harsh reality of a degenerating intervertebral disc. With respect to claim 19, Applicant argued that it is well established in the art of cellular biology that cryopreservation is notoriously cell-type dependent, and a cryopreservative formulation that yields high viability for the specific vaccine vectors or stem cells utilized in Strbo and Ra cannot be predictably extrapolated to successfully preserve an entirely different, complex mixture of two distinct cell types; and there is no teaching or suggestion in the prior art that the specific sucrose/DMSO carrier of Strbo/Ra would preserve the delicate synergistic functionality post-thaw.
First, since the above rejection was made under 35 U.S.C. 103 none of the cited references have to teach every limitation of the instant claims individually. For example, the primary Noh reference does not have to teach the use of a HEK (human embryonic kidney) cell as a first mammalian cell. It also appears that Applicant considered each of the cited references in total isolation one from the others, without taking into consideration at least the specific combination of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al as set forth above.
Second, in response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991). Please refer to the above modified 103 rejection for details along with the provided motivations for combining the cited references.
Third, as set forth in the above modified 103 rejection it would have been obvious for an ordinary skill in the art to modify the teachings of Noh et al by also at least treating a subject with a chronic back pain, including discogenic back pain; selecting and using human embryonic kidney cells such as HEK-293 cells that are inserted/transfected with a gene encoding a protein having intervertebral disc regenerating function such as a member of TGF-beta superfamily (e.g., TGF-beta 1, BMP) to be transplanted in a mixture with unmodified chondrocytes to induce/enhance cartilage, proteoglycans synthesis and/or cell proliferation of endogenous intervertebral disc cells and/or increased cartilage and proteoglycan production provided by the co-implanted unmodified chondrocytes at an intervertebral disc defect site in the subject; as well as irradiating the human embryonic kidney cells comprising an exogenous nucleotide sequence encoding a protein having an intervertebral disc regenerating function in a mixed cell population prior to administering the mixed cell population to the subject because: (a) Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain; (b) Harpstead already taught successfully using human epithelial cells (HeLa), human embryonic kidney cells (HEK) which provide an unlimited source of standardized, genetically homogenous cells, including transformed/genetically modified cells, that produce a therapeutic substance in a device to be implanted (e.g., at intervertebral site) in a patient in need thereof; (c) Thomas et al also taught that HEK293 cell line is of epithelial origin and it has many positive attributes that include: (i) quick and easy reproduction and maintenance, (ii) amenability to transfection using a wide variety of methods, (iii) high efficiency of transfection and protein production, and (iv) faithful translation and processing of proteins; (d) Masuda et al already reviewed the prior art literature and reported that growth factors such as TGF-beta1, BMP-2, OP-1/BMP-7 in the form of a recombinant protein and/or a recombinant expression vector increased proteoglycan and/or collagen synthesis, and/or increased cell proliferation in intervertebral disc cells in numerous cell and organ culture systems and in vivo models; and (e) Strbo et al already taught successfully the use of irradiated HEK293 cells that were transfected with the gp96-Ig-ZIKV antigen expression vector for the treatment of a flavivirus infection in a subject.
Fourth, with respect to the “wherein functional clinical outcome” clause since the modified treatment method resulting from the combined teachings of Noh et al, Freemont, Harpstead, Thomas et al, Masuda et al and Strbo et al has the same method steps and starting materials as those of the presently claimed invention, particularly the treatment method of Noh et al is already useful for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site in a mammal and Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain, such modified treatment method would naturally result at least in the reduction of discogenic back pain in the subject, reduction of a back pain-associated behavior, reduction in the sensitivity of the subject to the discogenic back pain, and/or reduction of TrpV1 or TrpA1-dependent calcium influx. Please, also note that where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke. Whether the rejection is based on "inherency" under 35 USC 102, or "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972). Moreover, please also note that the standard under 35 U.S.C. 103 is a “reasonable” expectation of success.
Fifth, an ordinary skill in the art would reasonably expect that an irradiated HEK cell would survive and stably express a therapeutic level of TGF-β in a mammalian intervertebral disc since with respect to irradiated HEK293 cells transfected with the gp96-Ig-ZIKV antigen expression vector Strbo et al already stated “Data shows that continuous cell secretion of gp96-Ig in vivo is more effective for CD8 CTL induction than injection of purified gp96-Ig” (first sentence of paragraph [0045]). Moreover, Song et al (Tissue Engineering 10:665-672, 2004; IDS) also demonstrated regeneration of hyaline articular cartilage with irradiated transforming growth factor Beta1-producing fibroblasts (Abstract). Once again, please note that the standard under 35 U.S.C. 103 is a “reasonable” expectation of success; and not certainty.
Sixth, there is no evidence of record indicating that the clinical outcome mediated by a mixed cell population comprising a HEK cell transfected with an exogenous nucleotide encoding a protein having an intervertebral disc regenerating function (e.g., TGF-β1) and a non-modified chondrocyte is synergistic or more than the combined clinical outcomes mediated by a cell population containing only a HEK cell transfected with an exogenous nucleotide encoding a protein having an intervertebral disc regenerating function (e.g., TGF-β1) and a cell population containing only a non-modified chondrocyte. On the contrary, the instant specification simply stated “Punctured intervertebral disc treated with untransduced chondrocytes alone, transduced 293 cells alone, primed chondrocyte alone or a mixture of transduced 293 cells and untransduced chondrocytes, show beneficial effects in preventing or retarding disc degeneration compared with vehicle control” (paragraph [00137] in Example IV). Please note that should there be any synergistic clinical outcome, it should be commensurate with the scope of the instant claims.
Seventh, with respect to claim 19 since Strbo et al already taught transfected HEK293 cells to be suspended in a freezing medium comprising 10% DMSO prior administration to a human subject, coupled with the teachings of Ra et al demonstrating that the cell viability for a stem cell therapeutic composition in frozen storage conditions was increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin, and 10% DMSO; an ordinary skill in the art would reasonably expect that a pharmaceutical carrier comprising about 10 to 20% w/w DMSO and about 1 to 5% w/w saccharose (sucrose) would also be at least suitable for the mixed cell population of the presently claimed invention. There is no objective evidence of record indicating or suggesting that the formulation containing 2% sucrose and 10% DMSO of Ra et al is unsuitable and/or detrimental in any way to a mixed cell population comprising a transduced HEK cell and a chondrocyte; and on the contrary such a formulation of Ra et al may provide a potential increased cell viability benefit. Once again, please note that the standard under 35 U.S.C. 103 is a “reasonable” expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer
Amended claims 1-19, 21 and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 14-19 and 23-24 of copending Application No. 18/134,401 (reference application) in view of Freemont (Rheumatology 48:5-10; 2009). This is a modified rejection necessitated by Applicant’s amendment.
The instant claims differ from claims 1-12 and 14-22 of copending Application No. 18/134,401 in reciting specifically “A method for treating chronic back pain in a subject”.
Before the filing date of the present application (04/13/2023), Freemont taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain (Abstract). Freemont stated “Studies examining the problem from different directions (e.g. examination of volunteers [4] and patients [5], imaging investigations [6], trials of intervention [7]) have produced evidence implicating the intervertebral disc (IVD) in a significant proportion (at least 40%) of cases of chronic back pain, leading to the use of the term “discogenic back pain”. From the work that has been carried out to date two processes stand out as being important in the origins of discogenic back pain, disc degeneration and nociceptive nerve ingrowth into the normally aneural IVD” (page 5, left column, second and third paragraphs in the “Introduction” section). Freemont also stated “Overall, current data indicate that normal IVD matrix prevents nerve ingrowth into the IVD, but that in degeneration changes in the structure of aggrecan, coupled with altered IVD cell biology lead to nerve ingrowth into pain level IVD and that this is enhanced by the production of neurogenic cytokines during neovascularization of the degenerate IVD” (page 8, left column, last paragraph).
Accordingly, it would have been obvious for an ordinary skilled artisan to modify the method for restoring a damaged or degenerating intervertebral disc in a subject in claims 11-12, 14-19 and 23-24 of copending Application No. 18/134,401 by also applying the method for treating a subject with a chronic back pain, including discogenic back pain, in light of the teachings of Freemont as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modification because Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain; and the method for restoring a damaged or degenerating intervertebral disc in a subject of the copending Application No. 18/134,401 would be useful and applicable.
An ordinary skilled artisan would have a reasonable expectation of success in light of claims 1-12, 14-19 and 23-24 of copending Application No. 18/134,401 along with the teachings of Freemont; coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified treatment method resulting from claims 1-12, 14-19 and 23-24 of copending Application No. 18/134,401 along with the teachings of Freemont as set forth above is indistinguishable and encompassed by the presently claimed invention. Since the modified treatment method has the same method steps and starting materials as those of the presently claimed invention, such modified treatment method would naturally result at least in the reduction of discogenic back pain in the subject, reduction of a back pain-associated behavior, reduction in the sensitivity of the subject to the discogenic back pain, and/or reduction of TrpV1 or TrpA1-dependent calcium influx.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
Amended claims 1-19, 21 and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 16-18 and 21-22 of copending Application No. 17/599,831 (reference application) in view of Noh et al (WO 2009/117740; IDS), Freemont (Rheumatology 48:5-10; 2009), Ra et al (US 2010/0196329) and Strbo et al (WO 2018/071405). This is a modified rejection necessitated by Applicant’s amendment.
The instant claims differ from claims 13, 16-18 and 21-22 of copending Application No. 17/599,831 in reciting specifically at least a method for treating chronic back pain in a subject; the human embryonic kidney cell or an epithelial cell is irradiated; the chondrocyte is primed by incubation with a cytokine such as TGF-beta1; the chronic back pain is a discogenic back pain; the ratio of the first mammalian cells and the second mammalian cells; and a pharmaceutical carrier comprising about 10 to 20% (w/w) DMSO and about 1 to 5% (w/w) saccharose.
Before the filing date of the present application (04/13/2023), Noh et al already disclosed at least a method for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site (e.g., torn or herniated) of a mammal, the method comprises: a) inserting a gene encoding a protein having intervertebral disc regenerating function (e.g., a member of TGF-beta superfamily such as TGF-beta1, BMP-2, BMP-3, BMP-4, BMP-7/OP-1 and others) into a first mammalian connective tissue cell, and b) transplanting a mixture of the mammalian connective tissue cell of a) and unmodified second mammalian connective tissue cell into the intervertebral disc defect site via injection; preferably the method does not use a scaffolding or any supporting structure for the cells; wherein the first and second mammalian connective tissue cell may be chondrocyte (e.g., non-disc chondrocyte, juvenile chondrocyte, and specifically the chondrocyte for the second mammalian connective tissue cell is a primed chondrocyte) or fibroblast; and either or both the first and second connective tissue cell may be autologous or allogeneic relative to the mammalian subject or to each other (paragraphs [0002], [0005], [0007], [0035]-[0036], [0043], [0047], [0052] and [00102]; Examples I and IV). Noh et al also taught that the ratio of cells that have not been transfected or transduced with a gene encoding a member of the transforming growth factor beta superfamily to cells that have been transfected or transduced with a TGF superfamily gene may be in the range of about 3-20 to 1, 3-10 to 1 or about 10 to 1 (paragraph [0028]). Noah et al also stated “ When these fibroblastic chondrocytes are incubated or “primed” with a cytokine such as a protein from the TGF-beta superfamily, the cells regain their chondrocytic characteristics, which include production of collagen” (paragraph [0046]); “An advantage of using primed cells in retardation of intervertebral disc degeneration is the ease of creating usable chondrocytes for introduction into the intervertebral disc for production of collagen and otherwise maintenance of the cartilaginous matrix” (paragraph [0047]); and “Alternatively, the cells may be incubated with the cytokine of interest for a time and the combination may be administered to the site of defect without separating out the cytokine” (paragraph [0050]). Noh et al further disclosed that a compound for parenteral administration to a patient in a therapeutically or prophylactically effective amount that includes a TGF-beta superfamily protein and a suitable pharmaceutically acceptable carrier (paragraphs [0058]-[0059]). Noh et al also taught that the connective tissue cell may be stored frozen in 10% DMSO in liquid nitrogen (paragraph [0063]), or in an exemplary cryopreservative media of DMEM, FBS and DMSO in a 5:4:1 ratio (last sentence of paragraph [00117]). In Example IV. 1, Noh et al taught the use of X-ray radiograph to obtain a disc height index of the intervertebral disc to measure its morphology, its level of degeneration or regeneration (paragraphs [0008], [00102]; and Fig. 1D-F); as well as the use of MRI (magnetic resonance image) radiograph to show healing, the slowing, retardation or prevention of degeneration of injured disc (paragraphs [0008], [[0093], 00102]; and Fig. 1A-C). An exemplified dose of a cell mixture comprising TGF-β1-producing chondrocytes and primary untransduced human chondrocytes is about 5 x 106 cells (Table 1 at page 24).
Additionally, Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain (Abstract). Freemont stated “Studies examining the problem from different directions (e.g. examination of volunteers [4] and patients [5], imaging investigations [6], trials of intervention [7]) have produced evidence implicating the intervertebral disc (IVD) in a significant proportion (at least 40%) of cases of chronic back pain, leading to the use of the term “discogenic back pain”. From the work that has been carried out to date two processes stand out as being important in the origins of discogenic back pain, disc degeneration and nociceptive nerve ingrowth into the normally aneural IVD” (page 5, left column, second and third paragraphs in the “Introduction” section). Freemont also stated “Overall, current data indicate that normal IVD matrix prevents nerve ingrowth into the IVD, but that in degeneration changes in the structure of aggrecan, coupled with altered IVD cell biology lead to nerve ingrowth into pain level IVD and that this is enhanced by the production of neurogenic cytokines during neovascularization of the degenerate IVD” (page 8, left column, last paragraph).
Moreover, Ra et al also disclosed at least a cell therapeutic composition comprising adipose-tissue derived mesenchymal stem cells and sucrose as an excipient, and wherein the composition further additionally comprising DMSO as the excipient (Abstract; Summary of the Invention; particularly paragraphs [0010]-[0014]). Ra et al stated “[w]hen the inventive cell therapeutic compositions containing adipose tissue-derived stem cells were stored under frozen storage conditions, the composition containing physiological saline, sucrose, albumin and cryopreservative DMSO showed the highest cell viability upon thawing, and it was observed that the addition of albumin and sugar components to the cell therapeutic composition protected the cells during the freezing and thawing of the cell to improve the viability of the cells” (paragraph [0048]). Ra et al demonstrated that the cell viability in frozen storage conditions was further increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin and 10% DMSO (Example 7, particularly paragraph [0065] and Table 3).
Furthermore, Strbo et al already taught the use of HEK293 cells that are transfected with the gp96-Ig-ZIKV antigen expression vector for the treatment of a flavivirus infection in a subject, wherein the transfected HEK293 cells were first irradiated (12,000 rads), then suspended in freezing medium comprising 10% DMSO, and 25% human serum albumin prior to subcutaneous administration to a patient (see at least Abstract; particularly paragraphs [0037]-[0039]).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the treatment method in claims 13, 16-18 and 21-22 of copending Application No. 17/599,831 by also having the above “features” recited in the claims of the present application; in light of the teachings of Noh et al, Freemont, Ra et al, and Strbo et al as set forth above with a reasonable expectation of success.
An ordinary skilled artisan would have been motivated to carry out the above modifications because: (i) Noh et al already taught to treat an intervertebral disc defect site (e.g., torn or herniated) of a mammal; the ratio of cells that have not been transfected or transduced with a gene encoding a member of the transforming growth factor beta superfamily to cells that have been transfected or transduced with a TGF superfamily gene may be in the range of about 3-20 to 1, 3-10 to 1 or about 10 to 1; and the chondrocytes may be incubated with the cytokine of interest (e.g., TGF-beta1) for a time and the combination may be administered to the site of defect without separating out the cytokine; (ii) Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain; (iii) Ra et al already demonstrated that the cell viability for a stem cell therapeutic composition in frozen storage conditions was increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin, and 10% DMSO; and (iv) Strbo et al already taught successfully the use of irradiated HEK293 cells that were transfected with the gp96-Ig-ZIKV antigen expression vector in a freezing medium comprising 10% DMSO and 25% human serum albumin for subcutaneous administration into a patient in need of a flavivirus infection treatment.
The modified treatment method resulting from claims 13, 16-18 and 21-22 of copending Application No. 17/599,831 along with teachings of Noh et al, Freemont, Ra et al and Strbo et al is indistinguishable and encompassed by the presently claimed invention. Since the modified treatment method has the same method steps and starting materials as those of the presently claimed invention, such modified treatment method would naturally result at least in the reduction of discogenic back pain in the subject, reduction of a back pain-associated behavior, reduction in the sensitivity of the subject to the discogenic back pain, and/or reduction of TrpV1 or TrpA1-dependent calcium influx.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
Amended claims 1-19, 21 and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-39 and 41 of copending Application No. 19/652,734 (reference application) in view of Noh et al (WO 2009/117740; IDS), Freemont (Rheumatology 48:5-10; 2009), Ra et al (US 2010/0196329) and Strbo et al (WO 2018/071405). This is a modified rejection necessitated by Applicant’s amendment.
The instant claims differ from claims 29-39 and 41 of copending Application No. 19/652,734 in reciting specifically at least a method for treating chronic back pain in a subject; the human embryonic kidney cell or an epithelial cell is irradiated; the chronic back pain is a discogenic back pain; the composition further comprising a cytokine such as a member of a TGF-β superfamily, the effective amount of the composition comprising the mixed cell population at a dose ranging from about 0.1 x 106 to about 100 x 106 cells; and a pharmaceutical carrier comprising about 10 to 20% (w/w) DMSO and about 1 to 5% (w/w) saccharose.
Before the filing date of the present application (04/13/2023), Noh et al already disclosed at least a method for preventing or retarding degeneration of intervertebral disc at an intervertebral disc defect site (e.g., torn or herniated) of a mammal, the method comprises: a) inserting a gene encoding a protein having intervertebral disc regenerating function (e.g., a member of TGF-beta superfamily such as TGF-beta1, BMP-2, BMP-3, BMP-4, BMP-7/OP-1 and others) into a first mammalian connective tissue cell, and b) transplanting a mixture of the mammalian connective tissue cell of a) and unmodified second mammalian connective tissue cell into the intervertebral disc defect site via injection; preferably the method does not use a scaffolding or any supporting structure for the cells; wherein the first and second mammalian connective tissue cell may be chondrocyte (e.g., non-disc chondrocyte, juvenile chondrocyte, and specifically the chondrocyte for the second mammalian connective tissue cell is a primed chondrocyte) or fibroblast; and either or both the first and second connective tissue cell may be autologous or allogeneic relative to the mammalian subject or to each other (paragraphs [0002], [0005], [0007], [0035]-[0036], [0043], [0047], [0052] and [00102]; Examples I and IV). Noh et al also taught that the ratio of cells that have not been transfected or transduced with a gene encoding a member of the transforming growth factor beta superfamily to cells that have been transfected or transduced with a TGF superfamily gene may be in the range of about 3-20 to 1, 3-10 to 1 or about 10 to 1 (paragraph [0028]). Noah et al also stated “ When these fibroblastic chondrocytes are incubated or “primed” with a cytokine such as a protein from the TGF-beta superfamily, the cells regain their chondrocytic characteristics, which include production of collagen” (paragraph [0046]); “An advantage of using primed cells in retardation of intervertebral disc degeneration is the ease of creating usable chondrocytes for introduction into the intervertebral disc for production of collagen and otherwise maintenance of the cartilaginous matrix” (paragraph [0047]); and “Alternatively, the cells may be incubated with the cytokine of interest for a time and the combination may be administered to the site of defect without separating out the cytokine” (paragraph [0050]). Noh et al further disclosed that a compound for parenteral administration to a patient in a therapeutically or prophylactically effective amount that includes a TGF-beta superfamily protein and a suitable pharmaceutically acceptable carrier (paragraphs [0058]-[0059]). Noh et al also taught that the connective tissue cell may be stored frozen in 10% DMSO in liquid nitrogen (paragraph [0063]), or in an exemplary cryopreservative media of DMEM, FBS and DMSO in a 5:4:1 ratio (last sentence of paragraph [00117]). In Example IV. 1, Noh et al taught the use of X-ray radiograph to obtain a disc height index of the intervertebral disc to measure its morphology, its level of degeneration or regeneration (paragraphs [0008], [00102]; and Fig. 1D-F); as well as the use of MRI (magnetic resonance image) radiograph to show healing, the slowing, retardation or prevention of degeneration of injured disc (paragraphs [0008], [[0093], 00102]; and Fig. 1A-C). An exemplified dose of a cell mixture comprising TGF-β1-producing chondrocytes and primary untransduced human chondrocytes is about 5 x 106 cells (Table 1 at page 24).
Additionally, Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain (Abstract). Freemont stated “Studies examining the problem from different directions (e.g. examination of volunteers [4] and patients [5], imaging investigations [6], trials of intervention [7]) have produced evidence implicating the intervertebral disc (IVD) in a significant proportion (at least 40%) of cases of chronic back pain, leading to the use of the term “discogenic back pain”. From the work that has been carried out to date two processes stand out as being important in the origins of discogenic back pain, disc degeneration and nociceptive nerve ingrowth into the normally aneural IVD” (page 5, left column, second and third paragraphs in the “Introduction” section). Freemont also stated “Overall, current data indicate that normal IVD matrix prevents nerve ingrowth into the IVD, but that in degeneration changes in the structure of aggrecan, coupled with altered IVD cell biology lead to nerve ingrowth into pain level IVD and that this is enhanced by the production of neurogenic cytokines during neovascularization of the degenerate IVD” (page 8, left column, last paragraph).
Moreover, Ra et al also disclosed at least a cell therapeutic composition comprising adipose-tissue derived mesenchymal stem cells and sucrose as an excipient, and wherein the composition further additionally comprising DMSO as the excipient (Abstract; Summary of the Invention; particularly paragraphs [0010]-[0014]). Ra et al stated “[w]hen the inventive cell therapeutic compositions containing adipose tissue-derived stem cells were stored under frozen storage conditions, the composition containing physiological saline, sucrose, albumin and cryopreservative DMSO showed the highest cell viability upon thawing, and it was observed that the addition of albumin and sugar components to the cell therapeutic composition protected the cells during the freezing and thawing of the cell to improve the viability of the cells” (paragraph [0048]). Ra et al demonstrated that the cell viability in frozen storage conditions was further increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin and 10% DMSO (Example 7, particularly paragraph [0065] and Table 3).
Furthermore, Strbo et al already taught the use of HEK293 cells that are transfected with the gp96-Ig-ZIKV antigen expression vector for the treatment of a flavivirus infection in a subject, wherein the transfected HEK293 cells were first irradiated (12,000 rads), then suspended in freezing medium comprising 10% DMSO, and 25% human serum albumin prior to subcutaneous administration to a patient (see at least Abstract; particularly paragraphs [0037]-[0039]).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the treatment method in claims 29-39 and 41 of copending Application No. 19/652,734 by also having the above “features” recited in the claims of the present application; in light of the teachings of Noh et al, Freemont, Ra et al, and Strbo et al as set forth above with a reasonable expectation of success.
An ordinary skilled artisan would have been motivated to carry out the above modifications because: (i) Noh et al already taught to treat an intervertebral disc defect site (e.g., torn or herniated) of a mammal using an exemplified dose of a cell mixture comprising TGF-β1-producing chondrocytes and primary untransduced human chondrocytes of about 5 x 106 cells; the chondrocytes may be incubated with the cytokine of interest (e.g., TGF-beta1) for a time and the combination may be administered to the site of defect without separating out the cytokine; (ii) Freemont already taught that molecular pathology has shown intervertebral disc (IVD) degeneration is a major cause of low back pain; (iii) Ra et al already demonstrated that the cell viability for a stem cell therapeutic composition in frozen storage conditions was increased in a formulation comprising physiological saline, PBS or Harman-D solution, as a base, 2% sucrose and 5% albumin, and 10% DMSO; and (iv) Strbo et al already taught successfully the use of irradiated HEK293 cells that were transfected with the gp96-Ig-ZIKV antigen expression vector in a freezing medium comprising 10% DMSO and 25% human serum albumin for subcutaneous administration into a patient in need of a flavivirus infection treatment.
The modified treatment method resulting from claims 29-39 and 41 of copending Application No. 19/652,734 along with teachings of Noh et al, Freemont, Ra et al and Strbo et al is indistinguishable and encompassed by the presently claimed invention. Since the modified treatment method has the same method steps and starting materials as those of the presently claimed invention, such modified treatment method would naturally result at least in the reduction of discogenic back pain in the subject, reduction of a back pain-associated behavior, reduction in the sensitivity of the subject to the discogenic back pain, and/or reduction of TrpV1 or TrpA1-dependent calcium influx.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
It is noted that in the Amendment filed on 03/25/2026 (pages 13-14), Applicant simply requested that all of the above provisional nonstatutory double patenting rejections be held in abeyance until an allowable subject matter is identified.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Moore et al (US 2013/0197094) disclosed administration of an effective amount of a TRPV1 compound at or near a target site to relieve pain caused by diverse sources, including postoperative pain, spinal disc herniation, discogenic back pain and joint pain (Abstract).
Conclusions
No claim is allowed.
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 Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s acting SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631
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