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 .
Claim Status
In the reply on 29 May 2026 Applicant has cancelled claims 2-4, 14, 22-23, 27-35. Therefore, claims 1, 5-13, 15-21, 24-26 are pending.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1 and 5-12, drawn to a cellular composition, comprising: a protectant in the reply filed on 29 May 2026 is acknowledged.
Applicant argues that the Examiner has not shown that a serious burden would result if all of the claims are examined together. However, this is not found persuasive because examiner was able to provide art which satisfied the limitations of the product claims without being able to satisfy the limitations of all the method claims thereby demonstrating that a search burden exists between the restricted groups.
Claims 13, 15-21, 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 5-12 are under current examination.
Priority
This application was filed 01/23/2024 and Claims Priority from Provisional Application 63481098 filed on 01/23/2023. Thus, the earliest possible priority for the instant application is 01/23/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/09/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Abstract Objection
The abstract of the disclosure filed 01/23/2024 is objected to because the abstract is only 34 words in length, and it is not submitted as a single paragraph on a separate sheet as required. Therefore, submitted abstract is considered non-compliant.
MPEP §608.01(b)(I) also sets forth guidelines for the abstract and states that “the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.”
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Therefore, appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, 8, 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kukekeov et al., (WO2009009020A1; published on: 15 January 2009; cited in PTO892; hereinafter “Kukekeov”).
Claim interpretation:
Claim 1 recites “wherein at least 90% of cells in the isolated mammalian nucleus pulposus (hereinafter “NP”) cells express CD9, and wherein at least 90% of cells in the isolated mammalian nucleus pulposus cells express CD109, wherein the isolated mammalian nucleus pulposus cells have an increased expression of CD9, CD 109, or both CD9 and CD 109 compared to the expression of CD9, CD109, or both CD9 and CD109 in premature nucleus pulposus cells.” The SPEC discloses that CD9+ NP cells are present in both healthy and degenerate tissue. Specifically, the percentage of CD9+ cells was significantly lower in degenerate compared to healthy discs (23% vs 79%) [00118]. SPEC further discloses, isolated NP cell population expressing CD9+, CD109+ or CD9+/CD109+ (SPEC [00122]) are expanding in the culture in presence of growth factors (i.e., TGF-b1, TGF-b3) (SPEC [00123]). Therefore, SPEC indicates that CD9 and CD109 are natural surface marker of NP cells. The examiner therefore, interprets the claimed limitation requiring that at least 90% of the isolated NP cells express CD9 and CD109 as encompassing NP cells have been enriched and expanded in culture. Furthermore, because the SPEC teaches expansion of isolated NP cells in the presence of TGF-beta growth factors, the examiner reasonably interprets the claimed “increased expression of CD9, CD109, or both CD9 and CD109 compared to premature NP cells” as referring to cultured and growth factor expanded NP cell populations that contain higher population of CD9+ and/or CD109+ cell that corresponding premature or non-expanded NP cell population.
Regarding claims 1, 10, Kukekeov teaches a cellular composition, comprising protectant (i.e., hydrogel [00135]), and isolated mammalian NP cells (e.g., an isolated disc stem cell of the present invention is derived from a NP of a subject. In another embodiment, NP cells comprise disc stem cells [0022]), wherein the isolated mammalian nucleus of pulposus cells have an extracellular matrix (ECM)-generating phenotype (claims 10-25, [00135], [00139], [00171]). Furthermore, Kukekeov teaches that the isolated healthy human NP tissue is cultured with growth factors in a culture medium [00164]-[00176] .
With respect to claims 1 and 5, MPEP 2112.01 states that “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established,” In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). it is noted that the claimed wherein clauses do not recite any additional active method steps, but simply state a function, characterization or measurement of the results of product positively recited (e.g., 90% of cells in the isolated mammalian NP cells express CD9 and/or CD109,). In here, Kukekeov et al., suggest producing the instant claim isolated NP cells specifically, using same cell culture method and healthy human NP tissue, so the process of making the product would have been anticipated. Furthermore, Kukekeov demonstrated high and low expression respectively indicating maturation of the disc tissue and again was found to be comparable to healthy controls [00187]. Accordingly, at the time of the invention POSITA would have expectation that the titer of the expressed CD9, CD109, and NC-specific ECM genes have increased expression compared to premature NP cells and this limitations are not unexpected.
Regarding claim 8, Kukekeov teaches that the mammalian nucleus pulposus cells comprise mature mammalian nucleus pulposus cells ([0026] of Kukekeov).
Accordingly, Kukekeov anticipates the instant claims 1, 5, 8, 10.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 5, 6-7, 8, 9, 10, and 11-12, are rejected under 35 U.S.C. 103 as being unpatentable by Kukekeov et al., (WO2009009020A1; published on: 15 January 2009; cited in PTO892; hereinafter “Kukekeov”), in view of Peck et al., (Scientific reports, 7(1), p.10504, 2017; cited in IDS filed 07/09/2024; hereinafter “Peck”).
As stated above, Kukekeov teaches a cellular composition, comprising protectant (i.e., hydrogel [00135]), and isolated mammalian NP cells (e.g., an isolated disc stem cell of the present invention is derived from a NP of a subject. In another embodiment, NP cells comprise disc stem cells [0022]), wherein the isolated mammalian nucleus of pulposus cells have an extracellular matrix (ECM)-generating phenotype (claims 10-25, [00135], [00139], [00171]). Furthermore, Kukekeov teaches that the isolated healthy human NP tissue is cultured with growth factors in a culture medium [00164]-[00176]. Kukekeov further anticipates at the time of the invention POSITA would have expectation that the titer of the expressed CD9, CD109, and NC-specific ECM genes have increased expression compared to premature NP cells and this limitations are not unexpected.
With respect to claim 6, Kukekeov does not specifically teach that the NP cells express one or more genes selected from the group consisting of ACAN, COL2AI, and COL6A3. However, such was known in the prior art.
Regarding claims 6-7, 9, 12, Peck teaches the ECM components of the notochord derived NP cells are important in supporting tissue structure and biomechanical function as well as for the binding and distribution of the many secreted growth factors that mediate tissue morphogenesis, homeostasis, repair, and remodeling. The ECM composition of the adult NP (specifically, resisting compressive forces) is COL2 and ACAN and both have been shown previously to be expressed in the NP during embryonic development. Peck further discloses the abundance of putative NP phenotypic markers shown previously to be expressed by immature and adult NP cells. Finally, Peck teaches several such markers that exhibited stable or increased expression across the E12.5 to P0 developmental window that may be the most faithful indicators of notochordal and early postnatal NP cell phenotypes (p. 11 of Peck).
Accordingly, it would have been obvious to practice the cellular composition of Kukekeov and include notochord derived NP cells as taught by Peck with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Peck because these adult NP cells do continue to maintain high expression of some notochordal markers that regulate embryonic disc formation, there is intense interest in identifying notochordal cell-secreted factors and applying them to develop improved therapeutic strategies for disc regeneration (p. 2, 1st and 4th ¶ of Peck). The POSITA would have had a reasonable expectation of success in combining the teachings of Kukekeov and Peck because each of these teachings both successfully develop improved therapeutic strategies for disc regeneration. Therefore, the products and method as taught by Kukekeov et al. in view of Peck et al. would have been prima facie obvious over the product of the instant application.
The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known product with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969). The invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made as evidenced by the teachings of Kukekeov et al. in view of Peck et al. especially in the absence of unexpected results.
Regarding claim 11, Kukekeov teaches Nucleus arthroplasty or nucleus replacement devices for degenerative spine disease consists of a hydrogel core center encased in a polyethylene sleeve which shrinks and swells during normal loading and unloading allowing for restoration of disc space height and thus mimicking healthy human disc ([005] of Kukekeov). Therefore, the disc replacement device comprises a hydrogel core in a flexible, inelastic, woven polyethylene jacket [0093], disc stem cells, disc progenitor cells, or a mixture thereof are introduced to the disc scaffold in a cell culture media comprising hydrogels and IGF-1 ([00135] of Kukekeov).
Regarding the protectant % (v/v) in the cellular composition Kukekeov does not particularly teach the limitation. However, it would have been obvious to POSITA to use sufficient amount of hydrogel with isolated mammalian nucleus pulposus cells taught by Kukekeov to treat intervertebral disc degeneration and/or back pain disorder in order to obtain desired therapeutic outcome of the method with a reasonable expectation of success. POSITA would recognize that the protectant % (v/v) in the cellular composition for the desired outcome in treating intervertebral disc degeneration having poor disc microenvironment and production of a proteoglycan-rich ECM is based on the amount of hydrogel use in between the disc as well as the number of NP cells used in the treatment in order to overcome the back pain in the subject, and the protectant % (v/v) would be modified by routine experimentations. Considering the limitation, with the known range of the enrichment based on the intervertebral disc activity, POSITA would be able to determine the protectant % (v/v) and number of cells in order to produce corrective therapy for the intervertebral disc degeneration and mimicking healthy human disc. In fact, Kukekeov teaches that additional hydrogels are added to the transplanted disc ([00150] of Kukekeov), and this would provide one skilled in the art a means to determine efficacy of treating intervertebral disc degeneration associated with poor disc microenvironment by adjusting the % (v/v) of the protectant and NP cells in order to produce effective therapy with a reasonable expectation of success.
Further, the choice of the % (v/v) of the protectant would be routine optimization. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144(II)(A).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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