DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8, 10-14, 16-18, and 28-31 were previously pending.
Receipt is acknowledged of the amendments to the claims submitted on 29 July 2026, and 31 July 2026. Claims 1, 3, 6, 11-13, and 17 are amended. Claims 4-5 are canceled. Claim 32 is newly added.
The restriction requirement mailed 18 December 2025 was previously made FINAL in the non-final rejection mailed 29 April 2026. Thus, claim 31 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1-3, 6-8, 10-14, 16-18, 28-30, and 32 are pending and under examination in the present Official Action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2022/004342, filed 28 January, 2022, which claims priority to Japan Application Nos. JP2021-013667 and JP2021-167913, filed 29 January, 2021, and 13 October, 2021 respectively. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified untranslated copies of papers required by 37 CFR 1.55 have been filed in this application on 21 July, 2023.
The earliest possible priority for the instant application is 21 July, 2023.
Drawings
The objection to the drawings is withdrawn in view of Applicant’s submission of replacement sheets. It is noted that figures are still presented in a form not readable by grey-scale. However, Applicant has argued that the drawings are the highest quality version available. Therefore, the drawings submitted on 29 July 2026 are accepted by the Examiner.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 32 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). It is noted that this is a warning and not an objection outright. Claim 1 is a method of treating by applying a composition. Claim 32 contains identical limitations to claim 1.
Claims 1, and 3 are objected to because of the following informalities: abbreviations/acronyms need to be spelled out upon their first encounter in the claims (for example: LNGFR, Thy-1). Appropriate correction is required.
Examiner Comment
Throughout the present Official Action, where reference is made to the instant Specification, the Examiner will be referring to the publication of the instant Application for ease of citation (US20240100099).
Withdrawn Objections/Rejections in view of Applicant’s amendments/Arguments
Claim Objections
The objection to claims 4-5, and 11 because of the following informalities: abbreviations/acronyms need to be spelled out upon their first encounter in the claims (for example: LNGFR, Thy-1, GPC-MALS) is withdrawn in view of Applicant’s amendments to the claims. Applicant has cancelled claims 4-5 and spelled out the abbreviations/acronyms in claim 11.
Claim Rejections - 35 USC § 102
The rejection of claims 1-3, 6-8, 10, 12-14, 16-18, and 28-30 under 35 U.S.C. 102(a)(1) as being anticipated by Ukeba, et al., EBioMedicine 53 (2020), hereinafter “Ukeba”, of record in the IDS filed 08 August, 2025 is withdrawn in view of Applicant’s amendments to the claims. Applicant has amended the claims to require the MSCs to be CD271 positive of CD271 and CD90 double-positive.
Maintained Rejections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112
Claims 3, 6-8, 10, 13, and 17 remain rejected and claims 1-2, 11-12, 14, 16, 18, 28-30, and 32 are newly rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Applicant has canceled claims 4-5 rendering the rejection of these claims moot. However, Applicant has moved the previously rejected language of claims 4-5 into claims 1, 3, and 32, necessitating the addition of the remaining claims under examination to this rejection.
The term “rapidly proliferating” in claims 1, 3, and 32 is a relative term which renders the claims indefinite. The term “rapidly proliferating” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Neither the claim nor the specification defines how rapid MSCs must proliferate to be considered “rapidly proliferating”. The specification contains a definitions section which does not in itself define “rapidly proliferating” and nowhere else in the specification is such a limiting definition presented. Therefore, the term is relative and a person having ordinary skill in the art would not be apprised of the scope of claims 1, 3, and 32. It is noted that this same rejection was presented in the non-final rejection of 29 April 2026 over previous claims 4-5. Applicant canceled those claims but did not address this issue when they added the term “rapidly proliferating” to claims 1, 3, and 32. Claims 2, 6-8, 10-14, 16-18, and 28-30 are further rejected for their dependency on a rejected base claim.
Claim 1 is indefinite in its recitation of “mesenchymal stem cell clones that are separated using, as an indicator, the feature that the cells are” because it is unclear if the claimed “cell population of rapidly proliferating mesenchymal stem cell clones” are positive for the claimed markers or the claimed markers are used to isolate and label a different cell population. As such the metes and bounds of the claim cannot be determined.
Claim 13 recites “wherein the application of the composition is effective for reducing intervertebral disc degeneration”. “Reducing” is a relative term which renders the claim indefinite. Neither the claim nor the specification defines “effective for reducing intervertebral disc degeneration” and a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought. Specifically, a person having ordinary skill in the art would not know how to assess the relative effectiveness nor how much degeneration would have to be reduced “compared to a subject without the treatment” in order to be effective and to fall within the scope of the claimed invention.
Response to Arguments
Applicant argues that “reducing intervertebral disc degeneration” in claim 13 is definite following the amendment which “provides an express comparative baseline for assessing reduction” (Remarks, page 10). This argument has been fully considered but has not been found persuasive because the claim and the specification are still lacking guidance for “reducing” and a person having ordinary skill in the art would still not know how to assess the relative effectiveness nor how much degeneration would have to be reduced “compared to a subject without the treatment” in order to be effective and to fall within the scope of the claimed invention. Accordingly, the argument has been fully considered but has not been found persuasive. It is recommended that Applicant replace “reducing” with -----treating-----.
Claims 1-3, 6-8, 10-14, 16-18, and 28-30 remain rejected and claim 32 is newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treating intervertebral disc degeneration, comprising: (i) injecting a liquid composition comprising a monovalent metal salt of alginic acid and mesenchymal stem cells into a nucleus pulposus of a damaged intervertebral disc; and (ii) spraying a solution of 102 mM CaCl2 onto the liquid composition, wherein the spraying of the solution of 102 mM CaCl2 induces gelation of the liquid composition, and wherein the composition comprises 2% weight volume of the monovalent metal salt of alginic acid and 1 x 106 mesenchymal stem cells per mL of the composition,
does not reasonably provide enablement for a method of treating any intervertebral disc comprising applying by any mechanism and in any form a composition comprising any amount of a monovalent metal salt of alginic acid and any amount of mesenchymal stem cells to the intervertebral disc of any subject in need thereof (reading on a method of prevention). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claims 1-3, 6-8, 10-14, 16-18, and 28-30 remain rejected and claim 32 is newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
While the written description and enablement requirements are separate and generally separable requirements, the instant application fails to meet either requirement for reasons which overlap significantly, as set forth below.
Applicant has amended the claims to require specific characteristics of the mesenchymal stem cells. However, the claims still read on any amount of the composition comprising any amount of mesenchymal stem cells wherein gelation is not required and wherein the composition isn’t required to be injected into the nucleus pulposus of an intervertebral disc. In addition, the claims now read on treating an intervertebral disc that is degenerated “and/or damage[d]” which reads on any conceivable form of damage (including damage caused by an over proliferation of cells in an intervertebral disc like that which occurs with cancer). Consequently, the amended claims have not come within the previously identified enabled claim scope in any of the ways presented in the non-final rejection of 29 April 2026.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of the Invention. The claims are drawn to a method of treating an intervertebral disc in a subject in need thereof comprising applying a composition wherein the composition comprises a monovalent metal salt of alginic acid and mesenchymal stem cells (MSCs).
2) Scope of the Invention. The scope of the instant invention is quite broad. A method of treating can broadly encompass any end-state which can be considered to treat a disease state while the claims themselves just require that a subject have damaged and/or degenerated intervertebral discs (including damage caused by an over proliferation of cells in an intervertebral disc like that which occurs with cancer). The claims also broadly read on any mechanism of application (implantation, injection to the exterior of the vertebrae, placed onto or sprayed at an exposed spine) of any form of the composition (liquid, solid, gaseous). The claims as recited read on a broad genus of methods in which gelation of the composition isn’t even required (raising issues of adequate written description as well as enablement). The claims also read on a composition having any amount of mesenchymal stem cells having the function of “treating an intervertebral disc” (raising issues of adequate written description as well as enablement) and any amount of alginic acid.
3) Number of Working Example and Guidance. The specification teaches several in vivo examples for the application of a composition to an intervertebral disc. The specification teaches the generation of an intervertebral disc (IVD) annulus fibrosis puncture rabbit model and the transplantation of a 2% (w/v) ultra-purified alginate (UPAL) solution containing BMSCs into a defect site in the nucleus pulposus of said models where the defect site was manually created by excising the nucleus pulposus ([0407]-[0409]). This example does not teach how many cells were in the UPAL but the specification teaches separately UPAL loaded with 1 x 106 BMSCs per mL of solution with an additional 1 x 106 nucleus pulposus cells per mL of solution ([0401]). Importantly, the specification teaches that 1mL of 102mM CaCl2 needed to be sprayed on top of the UPAL immediately after transplantation to induce gelling of the composition ([0409]). The specification teaches that the method in the rabbits resulted in increased collagen type II expression, and decreased type I collagen expression in the intervertebral disc ([0426]-[0427]). The specification also teaches the application of the method to sheep (Example 3). The specification is much more concise with regard to the method for sheep and merely states that BMSCs “suspended in UPAL at a final concentration of 1 x 106 cell/ml (100μl) were then injected into the voids in the intervertebral discs” ([0518]). Although this example does not specify the requirement for gelation, it is presumed to be a necessary step owing to the next Example in which sheep had 110 to 120 μL of a 2% UPAL solution containing 1 x 106 cell/ml of BMSCs transplanted into voids in their intervertebral discs immediately followed by injecting a 102 mM solution of CaCl2 onto the surface of the UPAL mixture ([0559]). The working examples again teach an increase in type II collagen expression and a decrease in type I collagen expression as the result of the method in sheep ([0593]). In the final working example, an identical method is performed on rats except the goal was to read out relative pain in the treated and untreated groups (Example 5). Notably, while the example in rats purports to show “a pain-suppressing effect”, no figures have been submitted in connection with the rat example to exemplify the findings of the three tests used to assess pain ([0672]). While the example describes what each of the three tests are, it stops short of teaching the results and instead just says that the data is “shown” without actually showing it ([0668]-[0671]). No example is provided in which a composition other than a 2% (w/v) UPAL solution containing 1 x 106 cell/ml of BMSCs is applied to an intervertebral disc in any manner other than via injection into the nucleus pulposus. No example is provided in which a composition is injected in any form other than as a liquid wherein gelation is induced by spraying a solution of CaCl2 onto the composition after transplanting. No example is provided in which any cells other than BMSCs were used. In addition, no example is provided in which any subject “in need thereof” is treated at all other than subjects in which their nucleus pulposus was excised and the result of transplantation was an increase in type II collagen expression with decreased type I collagen expression.
4) State of the Art. The state of the art for BMSC transplantation as a treatment for intervertebral disc degeneration goes as far back as 2006 (See Zhang, et al., Stem cell research & therapy 13.1 (2022): 70, hereinafter “Zhang”; See also Sakai, et al., " Biomaterials 27.3 (2006): 335-345, hereinafter “Sakai”). Zhang teaches the mechanism of intervertebral disc degeneration as involving a gradual degeneration of the nucleus pulposus cavity (Zhang, Fig. 1). Zhang also teaches various characteristics of different stem cell types that could be used to treat such a degeneration (Zhang, Table 1). With regard to in vivo application of stem cells to treat intervertebral disc degeneration, Zhang teaches autologous BMSCs transplanted into a rabbit model citing to Sakai as well as sheep, rat, and bovine models (Zhang, page 5, last partial paragraph; Table 3). Zhang also teaches that this technology has made the leap into human clinical trials (Zhang, page 6, first full paragraph). In this context, BMSCs were injected into the nucleus pulposus of human patients with varying success (Zhang, page 6, first full paragraph). Zhang also teaches that other MSC types like adipose-derived and umbilical cord MSCs have similarly been used in clinical trials with varying effectiveness (Zhang, Table 8). Thus, the injection of MSCs into the nucleus pulposus of intervertebral discs as a method of treating intervertebral disc degeneration is not new but appears to require specific steps which are not included in the claims.
5) Unpredictability of the Art. The art at the time of filing evidences unpredictability with respect to the use of alginate solutions of any concentration of alginate to treat intervertebral discs without the induction of gelation (See Bron, et al., Journal of the mechanical behavior of biomedical materials 4.7 (2011): 1196-1205, hereinafter "Bron"). Bron teaches that Alginate is frequently studied as a scaffold for intervertebral disc repair because it closely mimics the mechanical properties of the nucleus pulposus (Bron, Abstract). Bron also teaches that conditions like gelation temperature, type of crosslinker, and alginate concentration all influence the final mechanical properties of alginate scaffolds (Bron, page 1197, second full paragraph). Bron also teaches two types of gelation (both of which use calcium) wherein one is the diffusion method relied upon in the instant Application with some modifications (Bron, page 1197, last paragraph; page 1198, first paragraph). Bron teaches that 2% alginate scaffolds gelled by diffusion of Ca2+ diffusion most closely resembled the mechanical properties of a healthy nucleus pulposus around 11 kPa and that varying the concentration of alginate can vary the final kPa over 2 orders of magnitude in a relatively small range of concentrations (from 1 kPa to 100 kPa) (Bron, page 1201, “Discussion”). Thus, the skilled artisan at the time of filing knew that not just any concentration of alginic acid could be used to produce a scaffold for the treatment of an intervertebral disc with a defective nucleus pulposus and that gelation is required to produce the mechanical properties that most closely resemble a healthy nucleus pulposus.
This raises issues under description as well as enablement. The description component of the rejection is herein included as you cannot use what you have not described. The enablement of the instant invention has been assessed in light of the specification and the prior art available at the time of filing. "However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298,302 (CCPA 1971). (see MPEP 2164.08(b). Specifically, the claims read on a method of applying an alginate scaffold to an intervertebral disc in which gelation is not required and any amount of mesenchymal stem cells and any amount of alginic acid can be used. The skilled artisan, upon viewing the specification would conclude that the inventors here specifically injected a solution containing 1 x 106 BMSCs/ml and 2% (w/v) alginic acid into a damaged nucleus pulposus, then sprayed a 102mM CaCl2 solution on the alginate liquid to induce gelation. No other concentrations of BMSCs, no other concentrations of alginic acid, and no other method other than one including a gelation step was shown to have the effects of increased type II collagen expression and decreased type I collagen expression that Applicants and the art identify as being treating for damaged intervertebral discs. Thus, the genus claimed encompasses a significant number of inoperative embodiments in its encompassing any amount of mesenchymal stem cells, any amount of alginic acid, applies in any way, and not including a gelation step, having the function of “treating”.
Thus, the skilled artisan at the time of filing, upon viewing the supporting disclosure would not have concluded that the inventors were in possession of the genus of methods currently claimed.
6) Amount of Experimentation Required. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention.
Consequently, the art at the time of filing when combined with the lack of any disclosed direct experimental test of a method other than the specific method disclosed by Applicant and discussed above, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed methods of treatment could be identified given the lack of details necessary to identify those meeting the necessary functions. Though not controlling, the limitation of the working examples to a single method, is, nevertheless, a factor to be considered in a case involving physiological activity. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
Given the vast breadth of the genus of methods of treatment claimed, the unpredictability with respect to any amount of MSCs, any amount of alginic acid, applied in any way, not including a gelation step it must be considered that these variables must be empirically determined and that Applicants have only enabled what they have specifically shown as supported by the art at the time of filing. Further, in an unpredictable art, the disclosure of only a limited number of examples utilizing specific subjects treated with the same exact composition applied in the same way in every case requiring gelation would represent to the skilled artisan that Applicants were not in possession of the claimed genus.
Response to Arguments
Applicant argues that the amended claims are commensurate with the teachings of the specification (Remarks, page 11). Applicant specifically argues that requiring the MSCs to be CD271 positive or CD271 and CD90 double-positive with a coefficient of forward scattered light in flow cytometry of 40% or less or an average cell size of 20 μm or less is sufficient to provide an enabled claim scope (Remarks, page 11). Applicant also specifically argues that the specification expressly describes embodiments which do not require gelation (Remarks, page 12). These arguments have been fully considered but have not been found persuasive for the following reasons.
First, the standard for enablement is not whether the claims are commensurate in scope with the specification but rather whether undue experimentation would be required of a skilled artisan in order to practice the breadth of the invention as claimed when considering the guidance in the specification and the relevant art at the time of filing. It is noted that Applicant has not attempted to engage with the art at the time of filing that was cited by the Examiner (nor has Applicant provided contrary or contradictory art to refute the enablement rejection). Instead, Applicant has centered their arguments in favor of enablement solely on the amended claims and the specification. As discussed in the above rejection (and as discussed in the non-final rejection of 29 April 2026), the working examples provided by Applicant in the specification are quite limited. No example is provided in which a composition other than a 2% (w/v) UPAL solution containing 1 x 106 cell/ml of BMSCs is applied to an intervertebral disc in any manner other than via injection into the nucleus pulposus. No example is provided in which a composition is injected in any form other than as a liquid wherein gelation is induced by spraying a solution of CaCl2 onto the composition after transplanting. No example is provided in which any cells other than BMSCs were used. In addition, no example is provided in which any subject “in need thereof” is treated at all other than subjects in which their nucleus pulposus was excised and the result of transplantation was an increase in type II collagen expression with decreased type I collagen expression. While the specification may discuss the possibility of a method not requiring gelation, the specification only provides working examples where UPAL is used with a gelation step. Still further, Bron teaches that Alginate is frequently studied as a scaffold for intervertebral disc repair because it closely mimics the mechanical properties of the nucleus pulposus (Bron, Abstract). Bron also teaches that conditions like gelation temperature, type of crosslinker, and alginate concentration all influence the final mechanical properties of alginate scaffolds (Bron, page 1197, second full paragraph). Bron also teaches two types of gelation (both of which use calcium) wherein one is the diffusion method relied upon in the instant Application with some modifications (Bron, page 1197, last paragraph; page 1198, first paragraph). Bron teaches that 2% alginate scaffolds gelled by diffusion of Ca2+ diffusion most closely resembled the mechanical properties of a healthy nucleus pulposus around 11 kPa and that varying the concentration of alginate can vary the final kPa over 2 orders of magnitude in a relatively small range of concentrations (from 1 kPa to 100 kPa) (Bron, page 1201, “Discussion”). Thus, the skilled artisan at the time of filing knew that not just any concentration of alginic acid could be used to produce a scaffold for the treatment of an intervertebral disc with a defective nucleus pulposus and that gelation is required to produce the mechanical properties that most closely resemble a healthy nucleus pulposus. Accordingly, Applicant’s arguments in favor of enablement of the amended claims have been fully considered but have not been found to be persuasive.
Applicant argues against the written description portion of the instant rejection by arguing that there is support for the specific population of MSCs now claimed as well as support for “degeneration and/or damage” such that the specification reasonably conveys possession of the amended claim scope (Remarks, page 13). This argument has been fully considered but has not been found persuasive for the following reasons.
The claims’ breadth was not just established by the type of cells encompassed but also by the route of administration, the amount of the composition used, the number of cells within the composition, and the lack of a requirement for gelation of the composition. While Applicant has amended the claims to not read on a method of prevention, the method still reads on a vast genus of subjects having “degeneration and/or damage” of an intervertebral disc which encompasses damage caused by an over proliferation of cells in an intervertebral disc like that which occurs with cancer. Consequently, the amended claims still read on a vast genus of methods of treatment utilizing any amount of MSCs, any amount of alginic acid, applied in any way, not including a gelation step while the specification only teaches a limited number of examples utilizing specific subjects treated with the same exact composition applied in the same way in every case requiring gelation. Applicant has not addressed these issues through amendment or argument and the claims still read on a vast number of inoperative embodiments as exemplified in the above rejection. Accordingly, this argument has been fully considered but has not been found to be persuasive.
To the extent the claims read on the enabled claim scope identified above, the following rejections are applied.
Claim Rejections - 35 USC § 103
Claims 1 and 3 remain rejected and claims 2, 6-8, 10, 12-14, 16-18, 28-30, and 32 are newly rejected under 35 U.S.C. 103 as being unpatentable over Ukeba, et al., EBioMedicine 53 (2020), hereinafter “Ukeba”, of record in the IDS filed 08 August, 2025 in view of Mabuchi, et al., Stem cell reports 1.2 (2013): 152-165, hereinafter “Mabuchi”. This rejection has been modified as necessitated by Applicant’s amendments to the claims. Applicant has canceled claims 4-5 and moved those limitations into claims 1, 3, and 32.
Ukeba is a publication by several of the instant inventors. Ukeba discloses a method of treating degenerated intervertebral discs by injecting a 2% UPAL solution containing 1 x 106 BMSCs/ml into a cavity in the nucleus pulposus of a damaged intervertebral disc followed by injecting a 102mM CaCl2 solution on top of the UPAL/BMSC solution to induce gelation (Ukeba, Abstract; page 3, first full paragraph, and “2.8.” heading). UPAL is composed of sodium alginate which is a monovalent metal salt of alginic acid (Ukeba, page 2, “2.4.” heading).
Ukeba does not disclose the use of CD271 positive or CD271 and CD90 double-positive MSCs having at least one characteristic selected from the group consisting of a coefficient of variation of forward scattered light in flow cytometry of 40% or less and an average cell size of 20μm or less.
Mabuchi teaches the FACS isolation of an extremely pure population of MSCs from bone marrow which are LNGFR and Thy-1 positive (CD271 and CD90 positive respectively) (Mabuchi, Abstract; “Discussion” first paragraph; Figure 7). Mabuchi specifically teaches that the CD271+CD90+ BMSCs have increased clonogenic potential and that isolation of MSCs based on these two markers is a simple and easy method for obtaining extremely pure BMSCs (Mabuchi, “Discussion”, first paragraph). Regarding the characteristics recited in (a) and (b) of claims 1, and 32, it is noted 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, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess the claimed properties. See MPEP 2112.01. Here, Mabuchi teaches BMSCs having the exact cell parker profile claimed and teaches the selection of rapidly proliferating clones based upon their proliferation capacity (See Mabuchi Figure 1 and 3). Although Mabuchi acknowledges that “measurements of cell size (forward scatter)…failed to distinguish among the groups” (Mabuchi, page 158, first full paragraph), this does not detract from the fact that Mabuchi teaches to select BMSCs having the exact cell markers (CD271 and CD90) claimed and provides a motivation for doing so. These cells are presumed to inherently possess the characteristics recited in (a) and (b) of claims 1, and 32.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have selected CD271+CD90+ BMSCs via FACS as taught by Mabuchi and to have used those BMSCs in the method of repairing an intervertebral disc of Ukeba to arrive at the invention claimed in instant claims 1 and 32 with a reasonable expectation of success because they would have been motivated to do so to take advantage of a simple and easy method of isolating an extremely pure population of MSCs with high clonogenic potential.
Regarding claims 2 and 17, the limitations are inherent properties of the composition used in the claimed method. It is noted 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, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess the claimed properties. See MPEP 2112.01. Thus, the composition of Ukeba is presumed to inherently possess the claimed properties in claims 2 and 17. For completeness it is also worth noting that Ukeba discloses the MSCs activate and differentiate into nucleus pulposus cells (Ukeba, “Conclusions”).
Regarding claim 3, the MSCs of Ukeba are BMSCs. It is noted that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). Furthermore, “[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020). See also MPEP 2113. In the instant case, Mabuchi teaches the FACS isolation of an extremely pure population of MSCs from bone marrow which are LNGFR and Thy-1 positive (CD271 and CD90 positive respectively) (Mabuchi, Abstract; “Discussion” first paragraph; Figure 7). Mabuchi specifically teaches that the CD271+CD90+ BMSCs have increased clonogenic potential and that isolation of MSCs based on these two markers is a simple and easy method for obtaining extremely pure BMSCs (Mabuchi, “Discussion”, first paragraph), Mabuchi also teaches the single-cell culturing of BMSC clones (See Mabuchi Figure 1) and the selection of rapidly proliferating clones (Mabuchi, page 156, third full paragraph). Thus, the BMSCs taught by Mabuchi are the same as the BMSCs instantly claimed in the method of claim 3 because Mabuchi teaches an identical method of production for the BMSCs and to any extent the method of production may be argued to differ from the instantly claimed product-by-process limitations, the BMSCs will still be considered identical to those claimed for the purpose of applying prior art. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have selected CD271+CD90+ BMSCs via FACS as taught by Mabuchi and to have used those BMSCs in the method of repairing an intervertebral disc of Ukeba to arrive at the invention claimed in instant claim 3 with a reasonable expectation of success because they would have been motivated to do so to take advantage of a simple and easy method of isolating an extremely pure population of MSCs with high clonogenic potential.
Regarding claim 6, the composition is injected as a liquid (has fluidity) then gelation is induced after injection into a damaged intervertebral disc of a rabbit (subject in need thereof) (Ukeba, “2.6.”, “2.7.”, and “2.8.” headings).
Regarding claim 7, the composition of Ukeba is applied to the nucleus pulposus.
Regarding claim 8, the composition of Ukeba is filled into a defective site of the nucleus pulposus (Ukeba, “2.8.” heading).
Regarding claim 10, the UPAL has decreased endotoxicity (Ukeba, page 2, first partial paragraph).
Regarding claim 12, the concentration of alginic acid in Ukeba is 2% (w/v) (Ukeba, page 3, first full paragraph).
Regarding claim 13, Ukeba discloses the composition is effective in preventing intervertebral disc degeneration (Ukeba, “Research in Context” heading).
Regarding claim 14, Ukeba discloses treating intervertebral disc damage (Ukeba, “2.8.” heading).
Regarding claim 16, Ukeba uses CaCl2 as a crosslinking agent to induce gelation (Ukeba, “2.8.” heading).
Regarding claim 18, the BMSCs of Ukeba are in an undifferentiated state (Ukeba, “2.3.” heading).
Regarding claims 28-29, The limitations that "intervertebral disc damage [is] associated with chronic low back pain" and “used to suppress intervertebral disc pain” are intended uses. The prior art composition taught by primary reference is capable of performing the recited intended use and, therefore, these limitations are met. See e.g. In re Schreiber, 128 F.3d 1473, 1477; 44 USPQ2d 1429, 1431 (Fed. Cir. 1997); MPEP 2114.
Regarding claim 30, the crosslinking agent of Ukeba is Ca2+ which is a divalent metal ion.
Claims 1 and 11 remain rejected under 35 U.S.C. 103 as being unpatentable over US2020/0289547 (published: 17 September, 2020) (hereinafter “Sudo”) in view of Ukeba, et al., EBioMedicine 53 (2020), hereinafter “Ukeba”, of record in the IDS filed 08 August, 2025, and Mabuchi, et al., Stem cell reports 1.2 (2013): 152-165, hereinafter “Mabuchi”.
Sudo is another publication by the instant inventors. Sudo teaches a method of treating an intervertebral disc degeneration by injecting a composition comprising a monovalent metal salt of alginic acid into a nucleus pulposus of an intervertebral disc (Sudo, [0052]-[0053], [0239]). Sudo specifically teaches to use a monovalent metal salt of alginic acid which has an absolute molecular weight of 80,000 measured by GPC-MALS method (Sudo, [0037]). Sudo also teaches to use 0.5% to 5% w/w alginic acid concentration in the composition (Sudo, [0039]) and in particular a 2% w/v solution (Sudo, [0238]). Sudo also teaches to crosslink the composition with calcium ions (Sudo, [0042]-[0043]) and in particular a 102mM solution of calcium chloride (Sudo, [0239]). Lastly, Sudo suggests to include cells in the composition wherein the cells can be bone marrow mesenchymal stem cells in an amount between 1 x 104 and 1 x 107 cells per ml of the composition (Sudo, [0126]-[0128]).
While Sudo does not explicitly teach the composition to contain BMSCs, Sudo directly suggests to do so and directly suggests to use a concentration of cells which overlaps with the previously identified enabled claim scope. For determining how many cells and what particular type of cells to use in the composition of Sudo, a person having ordinary skill in the art would not have to look far because Ukeba provides these specific details and is also authored by the instant inventors. Ukeba discloses a method of treating degenerated intervertebral discs by injecting a 2% UPAL solution containing 1 x 106 BMSCs/ml into a cavity in the nucleus pulposus of a damaged intervertebral disc followed by injecting a 102mM CaCl2 solution on top of the UPAL/BMSC solution to induce gelation (Ukeba, Abstract; page 3, first full paragraph, and “2.8.” heading).
Sudo and Ukeba do not teach the use of CD271 positive or CD271 and CD90 double-positive MSCs having at least one characteristic selected from the group consisting of a coefficient of variation of forward scattered light in flow cytometry of 40% or less and an average cell size of 20μm or less.
Mabuchi teaches the FACS isolation of an extremely pure population of MSCs from bone marrow which are LNGFR and Thy-1 positive (CD271 and CD90 positive respectively) (Mabuchi, Abstract; “Discussion” first paragraph; Figure 7). Mabuchi specifically teaches that the CD271+CD90+ BMSCs have increased clonogenic potential and that isolation of MSCs based on these two markers is a simple and easy method for obtaining extremely pure BMSCs (Mabuchi, “Discussion”, first paragraph). Regarding the characteristics recited in (a) and (b) of claims 1, and 32, it is noted 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, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess the claimed properties. See MPEP 2112.01.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have used 1 x 106 BMSCs/ml as taught by Ukeba in the method of Sudo to arrive at the invention claimed in claims 1 and 11 with a reasonable expectation of success because Sudo directly suggests to include mesenchymal stem cells in an amount which overlaps with the enabled claim scope and Ukeba is published by the same instant inventors and teaches to use BMSCs at that concentration specifically. Further, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have selected CD271+CD90+ BMSCs via FACS as taught by Mabuchi and to have used those BMSCs in the method of repairing an intervertebral disc of Sudo and Ukeba to arrive at the invention claimed in instant claims 1 and 11 with a reasonable expectation of success because they would have been motivated to do so to take advantage of a simple and easy method of isolating an extremely pure population of MSCs with high clonogenic potential.
Response to Arguments
Applicant argues that (1) Ukeba does not disclose the specific cells required by the amended claims and Mabuchi does not teach applying an alginic acid composition to an intervertebral disc (Remarks, page 15), (2) Mabuchi does not teach the limitations recited in (a) and (b) of claims 1, and 32 (Remarks, page 15), (3) the present invention shows unexpected and remarkable results as reflected by [0157] and [0158], Figure 8, Table 3, and Figure 13 (Remarks, page 15), and (4) Sudo does not teach the specific BMSCs claimed and Ukeba does not supply the missing limitations (Remarks, page 16). These arguments have been fully considered but have not been found persuasive for the following reasons.
(1) and (4) In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The instant rejections are based upon a combination of Ukeba and Mabuchi as well as a combination of Ukeba, Mabuchi, and Sudo. Applicant’s arguments that each of the references is lacking in their individual capacities is unpersuasive here because each rejection was based on the combined teachings of the respective references. Accordingly, these arguments have been fully considered but have not been found persuasive.
(2) In response to Applicant’s argument that the prior art does not teach the limitations recited in (a) and (b) of claims 1, and 32, it is argued that the prior art does not need to teach these limitations explicitly for a prima facie case of obviousness to be established. 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, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess the claimed properties. See MPEP 2112.01. Here, Mabuchi teaches BMSCs having the exact cell parker profile claimed and teaches the selection of rapidly proliferating clones based upon their proliferation capacity (See Mabuchi Figure 1 and 3). Although Mabuchi acknowledges that “measurements of cell size (forward scatter)…failed to distinguish among the groups” (Mabuchi, page 158, first full paragraph), this does not detract from the fact that Mabuchi teaches to select BMSCs having the exact cell markers (CD271 and CD90) claimed and provides a motivation for doing so. In fact, Mabuchi even teaches an identical or at least substantially identical method for the isolation of the BMSCs. “Because validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020). See also MPEP 2113. In the instant case, Mabuchi teaches the FACS isolation of an extremely pure population of MSCs from bone marrow which are LNGFR and Thy-1 positive (CD271 and CD90 positive respectively) (Mabuchi, Abstract; “Discussion” first paragraph; Figure 7). Mabuchi specifically teaches that the CD271+CD90+ BMSCs have increased clonogenic potential and that isolation of MSCs based on these two markers is a simple and easy method for obtaining extremely pure BMSCs (Mabuchi, “Discussion”, first paragraph), Mabuchi also teaches the single-cell culturing of BMSC clones (See Mabuchi Figure 1) and the selection of rapidly proliferating clones (Mabuchi, page 156, third full paragraph). Thus, the BMSCs taught by Mabuchi are the same as the BMSCs instantly claimed in the method of claim 3 because Mabuchi teaches an identical method of production for the BMSCs and to any extent the method of production may be argued to differ from the instantly claimed product-by-process limitations, the BMSCs will still be considered identical to those claimed for the purpose of applying prior art. Thus, the BMSCs taught by Mabuchi are presumed to inherently possess the characteristics recited in (a) and (b) of claims 1, and 32. Accordingly, this argument has been fully considered but has not been found persuasive.
(3) In response to Applicant’s argument that the present invention shows unexpected and remarkable results as reflected by [0157] and [0158], Figure 8, Table 3, and Figure 13, evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). See also MPEP 716.02e. Here, Applicant has not attempted to make any such direct or indirect comparison, nor has Applicant submitted an affidavit or declaration to do so. Instead, Applicant has merely redirected attention back to figures already presented in the original disclosure. Such a showing is insufficient to rebut a prima facie case of obviousness. Of particular note, Applicant uses the same abbreviation for the cells used in the methods claimed (“RECs”) as that used in Mabuchi. This is not surprising since Mabuchi is one of the instant inventors. However, what is surprising is the presentation of an argument that the cells of the present invention are somehow different than the cells taught by the inventors in the Mabuchi publication without any direct or indirect comparison to Mabuchi and with the use of the very same label to designate the cell population. Accordingly, this argument has been fully considered but has not been found to be persuasive.
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.
Claims 1-3, 6-8, 10-14, 16-18, and 28-30 remain rejected and claim 32 is newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 12,478,636. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variant of the patented claims in view of Mabuchi, et al., Stem cell reports 1.2 (2013): 152-165, hereinafter “Mabuchi”.
Patented claim 1 reads: “A method of treating or reducing a degeneration and/or an injury of an intervertebral disc, wherein the degeneration and/or the injury comprises a defective site in a nucleus pulposus of the intervertebral disc, the method comprises applying to the defective site of a nucleus pulposus of an intervertebral disc in a subject in need thereof via a composition-filling inlet on the surface of the intervertebral disc a composition in a sol state to fill the defective site, the composition comprising a low endotoxin monovalent metal salt of alginic acid, and allowing a solid gel to form from a first portion of the composition after the applying by bringing a crosslinking agent into contact with the composition-filling inlet on the surface of the intervertebral disc, such that a second portion, which is other than the first portion, of the composition remains in the sol state, wherein the first portion corresponds to the surface of the composition located at the surface inlet and the second portion corresponds to the remainder of the composition other than the surface.”
Amended claim 1 reads: “A method of treating an intervertebral disc, comprising applying a composition comprising a monovalent metal salt of alginic acid and human bone marrow-derived mesenchymal stem cells to the intervertebral disc of a subject having intervertebral disc degeneration and/or damage, wherein the human bone marrow-derived mesenchymal stem cells are a cell population of rapidly proliferating mesenchymal stem cell clones that are separated using, as an indicator, the feature that the cells are LNGFR (CD271)-positive, or LNGFR (CD271) and Thy-1 (CD90) double-positive cells, said cell population satisfying at least one of the following characteristics (a) and (b): (a) the coefficient of variation of forward scattered light in flow cytometry is 40% or less; and (b) the average cell size is 20 pm or less.”
Patented claim 1 is related to instant claim 1 as a species of the genus instantly claimed with the exception of the instant claims requiring mesenchymal stem cells in the composition. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). With regard to the requirement for mesenchymal stem cells in the composition, note that MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for ODP rejections.
In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. The court in AbbVie Inc. v. Kennedy Institute of Rheumatology Trust pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
In the instant case, the patent specification teaches that the composition can comprise mesenchymal stem cells (col. 14, lines 46-50). Thus, the instantly claimed composition is an obvious variant of the composition claimed in the patent with regard to the inclusion of mesenchymal stem cells in the composition in the method of treating.
With regard to the limitations requiring the BMSCs to be CD271 positive of CD271 and CD90 double-positive, Mabuchi teaches the FACS isolation of an extremely pure population of MSCs from bone marrow which are LNGFR and Thy-1 positive (CD271 and CD90 positive respectively) (Mabuchi, Abstract; “Discussion” first paragraph; Figure 7). Mabuchi specifically teaches that the CD271+CD90+ BMSCs have increased clonogenic potential and that isolation of MSCs based on these two markers is a simple and easy method for obtaining extremely pure BMSCs (Mabuchi, “Discussion”, first paragraph). Regarding the characteristics recited in (a) and (b) of claims 1, and 32, it is noted 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, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Thus, for the purpose of applying prior art, a disclosure of an identical or substantially identical product is presumed to inherently possess the claimed properties. See MPEP 2112.01. Here, Mabuchi teaches BMSCs having the exact cell parker profile claimed and teaches the selection of rapidly proliferating clones based upon their proliferation capacity (See Mabuchi Figure 1 and 3). Although Mabuchi acknowledges that “measurements of cell size (forward scatter)…failed to distinguish among the groups” (Mabuchi, page 158, first full paragraph), this does not detract from the fact that Mabuchi teaches to select BMSCs having the exact cell markers (CD271 and CD90) claimed and provides a motivation for doing so. These cells are presumed to inherently possess the characteristics recited in (a) and (b) of claims 1, and 32.
Therefore, the amended claims are obvious over the patented claims in view of Mabuchi.
Response to Arguments
Applicant argues that the patented claims do not require “(a) the coefficient of variation of forward scattered light in flow cytometry is 40% or less” or “(b) the average cell size is 20 μm or less” and they do not require the CD271 positive or CD271 and CD90 double-positive cell characteristics (Remarks, page 17). This argument has been fully considered but has not been found persuasive because Mabuchi teaches these characteristics and teaches BMSCs obtained by an identical or substantially identical process (See above). Therefore, the pending claims are still rejected under non-statutory double patenting in view of the reference patent and Mabuchi.
Conclusion
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 BRENDAN THOMAS TINSLEY whose telephone number is (703)756-5906. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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