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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/10/2026 has been entered.
Status of Claims
Claims 9-10 are examined on the merits herein.
Claim 9 is currently amended.
Claims 17, 22, and 24-29 are withdrawn from consideration as being drawn to inventions non-elected without traverse in the reply filed on 05/23/2025.
Priority
The instant application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2020/035517, filed 09/18/2020, which claims priority to JAPAN 2020-062441, filed 03/31/2020, and JAPAN 2019-169278, filed 09/18/2019. 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 03/17/2022.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
The earliest possible priority for the instant application is 09/18/2019.
Claim Interpretation
Claim 9 is drawn to “A mammalian chondrocyte progenitor cell population.” The broadest reasonable interpretation of “cell population” includes a population of two cells.
Absent a specific definition in the specification, the term “chondrocyte progenitor cell” is given its broadest reasonable interpretation in the art, which is a cell that exhibits differentiation capacity into a chondrocyte, including a mesenchymal stem cell.
Claim 9 is a product-by-process claim. Product-by-process claims are not limited to the
manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113. In the instant
case, the method step of claim 9 (induced from a mammalian iPS cell, line 2) does not clearly impart additional structural limitations to the claimed mammalian chondrocyte progenitor cell population.
Claim 9 recites the limitation “having the same karyotype as the mammalian iPS cell” (lines 2-3). It is noted that a mammalian iPS cell may have a wild-type karyotype or display chromosomal aberrations.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9-10 remain 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.
Claim 9 is drawn to “A mammalian chondrocyte progenitor cell population… consisting of a uniform cell population” (lines 1-3). It is unclear whether “a uniform cell population” (line 3) refers to “a mammalian chondrocyte progenitor cell population” (lines 1-2), or whether it refers to a sub-population of cells within the mammalian chondrocyte progenitor cell population of lines 1-2.
The phrase “consisting of” (line 3) suggests the first interpretation, which amounts to “A mammalian chondrocyte progenitor cell population… wherein the cell population is detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity.” However, it is then unclear what additional limitations, if any, is to be imposed on the cell population by the phrase “a uniform cell population” (line 3).
Claim 10 is included in the rejection because it depends from claim 9.
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.
Claim 9 remains rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lu (Journal of Bone and Mineral Research, 2011, 26(1): 209-219), as evidenced by Tang (PNAS, 2004, 101(26): 9607-9611) and Roson-Burgo (BMC Genomics, 2016, 17: 944).
Lu teaches primary stromal cells (MSCs) and C3H10T1/2 mouse pluripotent mesenchymal cells (both cell types read on a mammalian chondrocyte progenitor cell) that are positive for Prx1 expression (Abstract; p 213, col 2, para 2; Fig 2). Lu teaches that Prx1 is also known as Prrx-1 (Title; p 213, col 1, para 1).
Tang shows that C3H10T1/2 cells are pluripotent stem cells (Abstract; p 9607, col 1, para 3).
Roson-Burgo shows that mesenchymal stem cells and other stem cells are positive for CD90 and CD140B (p 8, Table 1; p 19, col 1, para 1).
Therefore, the PRRX1-positive MSCs and C3H10T1/2 stem cells taught in Lu are also positive for CD90 and CD140B.
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.
Claims 9-10 remain rejected under 35 U.S.C. 103 as being unpatentable over Lu (Journal of Bone and Mineral Research, 2011, 26(1): 209-219), as evidenced by Tang (PNAS, 2004, 101(26): 9607-9611) and Roson-Burgo (BMC Genomics, 2016, 17: 944), in view of Collins (US 2009/0029463 A1).
The teachings of Lu, as wells as the evidence from Tang and Roson-Burgo, are set forth above. Lu, as evidenced by Tang and Roson-Burgo, anticipates claim 9.
Regarding claim 10: Lu does not teach cryopreserving the mammalian chondrocyte progenitor cell population of claim 9.
Collins teaches that chondrocyte progenitor cells can be cryopreserved to allow for long-term storage of the cells for therapeutic use (para 2, 18, 46).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the mammalian chondrocyte progenitor cell population of Lu by cryopreserving them, as taught in Collins. One of ordinary skill in the art would have been motivated to make this modification because Collin teaches that cryopreservation allows for long-term storage of the cells for therapeutic use. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Collins teaches that chondrocyte progenitor cells can be cryopreserved.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 9-10 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (specifically, a natural phenomenon) without significantly more.
The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. Claim 9 is interpreted as “A mammalian chondrocyte progenitor cell population comprising at least two cells, wherein the cell population is detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity.”
Step 1: This part of the eligibility analysis evaluates whether the claim falls within any statutory category. MPEP 2106.03. Here, the claims recite a mammalian chondrocyte progenitor cell population. Because a mammalian chondrocyte progenitor cell population is a composition of matter, the claims 9-10 fall within a statutory category. (Step 1: YES)
Step 2A, Prong One: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. Because claims 9-10 recite a nature-based product limitation, the markedly different characteristics analysis is used to determine if the nature-based product limitation is a product of nature exception. MPEP 2106.04(c)(I). MPEP 2106.04(c)(I)(A). The markedly different characteristics analysis is performed by comparing the nature-based product limitation in the claim to its naturally occurring counterpart to determine if it has markedly different characteristics from the counterpart. MPEP 2106.04(c)(II).
Here, the closest natural counterpart to mammalian chondrocyte progenitor cell populations of claims 9-10 is a naturally occurring PRRX1+, CD90+, and CD140B+ mammalian chondrocyte progenitor cell population, per se. The art, as exemplified in Lu (Journal of Bone and Mineral Research, 2011, 26(1): 209-219) and Deng (eLife, 2019: e50208), teaches that murine mesenchymal stem/stromal cells (MSCs) are positive for PRRX1 (e.g., Abstract and Fig 2 of Lu; Abstract of Deng). Roson-Burgo (BMC Genomics, 2016, 17: 944) shows that mesenchymal and other stem cells are positive for CD90 and CD140B (Table 1; p 19, col 1, para 1). The claimed mammalian chondrocyte progenitor cell population is identical to a naturally occurring mammalian chondrocyte progenitor cell population, thus there is no marked difference between the claim and product of nature. Accordingly, the claims recite a judicial exception, and the analysis must therefore proceed to Step 2A, Prong Two.
Step 2A, Prong Two: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. 2019 PEG Section III(A)(2), 84 Fed. Reg. at 54-55.
Claim 9 does not integrate the product into a practical application because the claims are to a mammalian chondrocyte progenitor cell population, per se, and do not recite additional elements beyond the judicial exception. (Step 2A: YES)
Claim 10 is drawn to a mammalian chondrocyte progenitor cell population, which is cryopreserved. The additional element of a cryoprotectant does not integrate into the mammalian chondrocyte progenitor cell population, and therefore does not add a meaningful limitation to the claim. The cryoprotectant is merely a nominal or token extra-solution component of the claim and is nothing more than an attempt to generally link the product of nature to a particular technological environment. Therefore, the claim does not integrate the product into a practical application (Step 2A: YES).
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05.
Claim 9 does not recite any elements in addition to the judicial exception of a mammalian chondrocyte progenitor cell population, so there are no additional elements that add significantly more to the judicial exception. (Step 2B: NO)
Claim 10 is drawn to a mammalian chondrocyte progenitor cell population, which is cryopreserved. The presence of a cryoprotectant does not alter the mammalian chondrocyte progenitor cell population. Luetzkendorf (Cryotherapy, 2015, 17: 186-198) teaches that cryopreservation does not alter the main characteristics, including viability, of human multipotent mesenchymal stromal cells (Abstract). The addition of a cryoprotectant to a cell population is a well-understood, routine, and conventional activity in the art. Therefore, the claim does not include additional elements that are sufficient to amount to significantly more (also known as an “inventive concept”) than the judicial exception of a mammalian chondrocyte progenitor cell population. (Step 2B: NO).
The claims are not patent eligible.
Response to Arguments
RE: Rejections under 35 U.S.C. 102
Applicant argues: Lu et al. discloses that murine primary stromal cells and C3H10T01/2 cells only express Prx1 under certain conditions. Specifically, Lu et al. discloses that (a) C3H10T01/2 cells stimulated with exogenous TNF-α exhibit robust levels of PRX1a and PRX1b expression but (b) unstimulated C3H10T01/2 cells show low levels of PRX1a and PRX1b expression (page 213, right column, second paragraph, and Figures 2A and 2B). Therefore, even if some of C3H10T01/2 cells disclosed by Lu et al. are PRRX1 positive, Lu et al. provides no evidence that the C3H10T01/2 cells are a uniform cell population detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity, as recited in claim 9 as amended herein.
In response: Applicant’s arguments have been fully considered, but are not persuasive. First, Lu teaches treating one population of C3H10T01/2 cells with exogenous TNF-α exhibit (population A), and another population of untreated C3H10T01/2 cells (population B). Lu teaches that cells of population A exhibit robust levels of PRX1a and PRX1b expression. Furthermore, even if only a subset of the treated cells of population A exhibited PRX1a and PRX1b expression, one could isolate said PRX1-positive cells from population A, thus arriving at a population of cells that all express PRX1.
Applicant argues: While Lu et al. recites in the abstract that "PCR revealed Prx1expression in primary stromal cells (MSCs), C3Hl00Tl/2 cells, and MC3T3 preosteoblasts," this statement is not supported elsewhere in Lu et al. Rather, Lu et al. only discloses results using MSC cells in the context of transfection with exogenous PRX1a or PRX1b expression vectors (page 216, left column, first paragraph, and Figure 8). Lu et al. also discloses that MSCs were prepared using young-adult C57BL/6 male mice but states that PRX1 is expressed in developing mouse mesenchyme until embryonic day 11.5, after which levels are reduced. This disclosure suggests that PRX1 levels would be low or absent in the young adult mice used to prepare MSCs by Lu et al.
In response: Applicant’s arguments have been fully considered, but are not persuasive. Regarding the disclosure in the Abstract of Lu, the Examiner agrees with Applicant that Lu only discloses experimental data from PCR for PRX1 expression in C3Hl00Tl/2 cells, and not in primary stromal cells (MSCs). Despite the lack of disclosure of experimental data, however, Lu does disclose in the Abstract that primary stromal cells (MSCs) express PRX1. Moreover, it is noted that Lu does disclose experimental data regarding PRX1 expression in C3H100T1/2 cells, which also read on the cell population of claim 9.
Regarding the expression of PRX1 in MSCs derived from young-adult C57BL/6 male mice, it is noted that even low PRX1 expression satisfies the limitation of PRX1 positivity, as required by instant claim 9.
Applicant argues: Tang et al., and Roson-Burgo et al. are silent with respect to the expression of PRRX in C3Hl0T0l/2 cells and MSC cells. Therefore, none of Lu et al., Tang et al., and Roson-Burgo et al. disclose or suggest a uniform cell population detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity, as recited in claim 9 as amended herein.
In response: Applicant’s arguments have been fully considered, but are not persuasive. Gene Cards, Tang, and Roson-Burgo are evidentiary references to show that C3H10T1/2 cells are pluripotent stem cells (Tang), and that stem cells are positive for CD90 and CD140B (Roson-Burgo). The limitation regarding PRRX1 expression is taught in Lu.
RE: Rejections under 35 U.S.C. 103
Applicant argues: Lu et al. does not disclose or suggest a uniform cell population as recited in claim 9. Collins does not remedy this shortcoming of Lu et al. as Collins also does not disclose a uniform cell population detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity.
In response: Applicant’s arguments have been fully considered, but are not persuasive. The arguments regarding Lu and the limitations of claim 9 have been addressed above. Collins is relied upon for the limitation regarding cryopreservation in claim 10, not the limitations of claim 9.
Applicant argues: The multi-lineage progenitor cells (MLPCs) disclosed by Collins are distinct from the iPS cells recited in claim 10. As disclosed in the present application, iPS cells have complete pluripotency, i.e., the ability to differentiate into all somatic and germline cells (paragraphs 0021, 0026, and 0027). In contrast, while MLPCs are able to differentiate into a number of different cell types, MLPCs are not considered pluripotent.
In response: Applicant’s arguments have been fully considered, but are not persuasive. First, Collins is not relied upon for the rejection of claim 9.
Moreover, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a population of iPSCs) are not recited in the rejected claim(s). Claim 9 is drawn to “a mammalian chondrocyte progenitor cell population induced from a mammalian iPS cell,” not to “a mammalian iPS cell population.” As noted under Claim Interpretation, the method step of claim 9 (induced from a mammalian iPS cell, line 2) amounts to a product-by-process limitation, which does not clearly impart additional structural limitations to the claimed mammalian chondrocyte progenitor cell population. Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113.
Applicant argues: While Collins discloses that MLPCs can express CD90, Collins does not disclose that MLPCs express CD 140B or PRRX1. Therefore, a person of ordinary skill in the art would not have been motivated to use the method of cryopreservation of MLPCs as disclosed by Collins on murine primary stromal cells and C3Hl0T0l/2 cells as disclosed by Lu et al., let alone iPS cells as required by the present invention.
In response: Applicant’s arguments have been fully considered, but are not persuasive. The murine primary stromal cells and C3H10T01/2 cells taught in Lu are chondrocyte progenitor cells. Collins teaches that chondrocyte progenitor cells can be cryopreserved to allow for long-term storage of the cells for therapeutic use (para 2, 18, 46). Thus, one of ordinary skill in the art would have been motivated to cryopreserve the chondrocyte progenitor cells of Lu, according to the teachings of Collins.
RE: Rejections under 35 U.S.C. 101
Applicant argues: Because human cartilage progenitor cells (hCPCs) coexist with other
cell types in the human body, the human body has no naturally occurring mammalian chondrocyte progenitor cell population "consisting of a uniform cell population detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity," as required by claims 9 and 10.
In response: Applicant’s arguments have been fully considered, but are not persuasive. As set forth in the rejection of claim 9 under 35 USC 112(b) in the instant Office Action, it is not clear what additional limitation is imposed on the cell population of claim 9 by the phrase “a uniform cell population detected as a single peak in flow cytometry.” A single peak in flow cytometry does not imply that all the cells in a population exhibit the identical expression level for a given marker. For example, a population of cells, in which most cells express PRRX1 to varying degrees, may still exhibit a single peak in flow cytometry. Thus, naturally occurring murine mesenchymal stem/stromal cells (MSCs) in a mouse body, which is positive for PRRX1, CD90, and CD140B, satisfies the limitations of claim 9.
Applicant argues: The present application discloses that, by using a mammalian chondrocyte progenitor cell population consisting of a uniform cell population detected as a single peak in flow cytometry analysis using respective antibodies against PRRX1, CD90, and CD140B, and satisfying conditions of PRRX1 positivity, CD90 positivity, and CD140B positivity, high-quality chondrocytes and cartilage tissue suitable for transplantation can be obtained (see, e.g., specification paragraph 0051).
In response: Applicant’s arguments have been fully considered, but are not persuasive. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art or a product of nature.
Moreover, it is noted that the features upon which applicant relies (i.e., the intended use of the cell population) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/ Examiner, Art Unit 1632
/KARA D JOHNSON/ Primary Examiner, Art Unit 1632
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