The Patent Trial and Appeals Board (PTAB), a creation of the Leahy-Smith America Invents Act that replaced the Board of Patent Appeals and Interferences (BPAI) overruled the Reexamination Unit's decision that the claims of U.S. Patent No. 6,777,231 were invalid for failing to satisfy the written description and enablement requirements of 35 U.S.C. § 112(a) in University of Pittsburgh v. Cellerix (the Third Party Requestor being succeeded in interest by TiGenix SAU) (Appeal 2013-008103; Reexamination Control 95/001,592). All was not well for the University Patent Owner, however, because the Board also reversed the Reexamination Unit's refusal to consider whether the claims of the '231 patent were inherently anticipated by three prior art references, remanding the reexamination under 37 C.F.R. § 41.77(b).
The technology involves stems cells from adipose tissue. Representative claims include:
1. An isolated adipose-derived stem cell that can differentiate into two or more of the group consisting of a bone cell, a cartilage cell, a nerve cell, or a muscle cell.
5. A substantially homogeneous population of adipose-derived stem cells, comprising a plurality of the stems cells of claims 1, 3 or 4.
6. The adipose-derived stem cell of claim 1, 3 or 4 which can be cultured for at least 15 passages without differentiating.
11. The adipose-derived stem cell of claim 6, wherein the cell can be cultured in DMEM and 5-15% serum without losing the capacity to differentiate.
12. An isolated adipose-derived stem cell that can differentiate into two or more of the group consisting of a bone cell, a cartilage cell, a nerve cell, or a muscle cell, wherein the isolated adipose-derived stem cell is substantially free of other adipose tissue cells and extracellular material.
17. The adipose-derived stem cell of claim 12, 14 or 15 which can be cultured for at least 15 passages without differentiating.
22. The adipose-derived stem cell of claim 17, wherein the cell can be cultured in DMEM and 5-15% serum without losing the capacity to differentiate.
23. The substantially homogeneous population of claim 5, wherein adipose-derived stem cells therein can be cultured for at least 15 passages without differentiating.
25. The substantially adipose-derived adipose-derived stem cell of claim 23, wherein the cell can be cultured in DMEM and 5-15% serum without losing the capacity to differentiate.
28. The substantially homogeneous population of claim 26, wherein adipose-derived stem cells therein can be cultured in DMEM and 5-15% serum withoit losing the capacity to differentiate.
The case came to the Board on appeal by the Patent Owner that the Examiner had erred in rejecting claims 11 and 25 for failing the enablement and written description requirements, and cross appeal from the Third Party Requestor that the Examiner erred in refusing to adopt rejection of claims 11, 22, 25, and 28 as being inherently anticipated.
The Board, in an opinion by APJ Lebovitz joined by APJ's Green and Guest, first addressed the Examiner's claim construction, applying the principle that the claims should be given their broadest reasonable interpretation (consistent with the ex parte examination standard). For claims 11 and 25, claims rejected for failure to satisfy the requirements of § 112(a), the Board construed the claims to contain all the limitations recited in each of the patent claims from which the claims depended, which the Board stated were that these cells "must be capable of differentiating into two or more cell types and of being cultured for at least 15 passages without differentiating." According to the Board, the specification defined the meaning of the phrase "without losing the capacity to differentiate" as: "'the capacity to differentiate' means (for the purposes of construing these claims) 'the ability of the [] cell to differentiate into two or more of the cell types [] of a fat cell, a bone cell, a cartilage cell, a nerve cell or a muscle cell.'" (The Board determined that the skilled worker would understand that "DMEM" meant Dulbecco's Modified Eagle's Medium.) The Board noted that the claim does not specify how long the stem cell must retain this capacity to differentiate, but that the Examiner (and the Third Party Requestor) contended that it had to be at least 15 passages. But the Board cited the specification for disclosing that the cells are passaged at least 5, 10, 15, or 20 times. And the Board noted that while claims 6 and 23 recited culturing for 15 passages they did not specify the culture media, and claims 11 and 25 recited culturing the cells in DMEM but not the number of passages. According to the opinion there was no "antecedent basis" that would link the claims together, and that as composition claims (as opposed to method claims) the recited limitations are capabilities not "actual steps [that have been] taken." Thus, there was no justification to construe claims 11 and 25 to require 15 passages.
Having construed these aspects of the claims, the Board then turned to the grounds of rejection under § 112(a). With regard to the written description requirement, the Board rejected the Examiner's conclusion that the claims were unpatentable because the specification failed to describe culturing stem cells that retained the capacity to differentiate upon passage in culture, but rather that cells could be cultured wherein they did not differentiate. According to the Board, the Examiner erroneously found this deficiency because the Examiner interpreted the claim to "require that the cell's capacity to differentiate must be the same at the beginning and the end of the culture," which it was undisputed the specification did not do. Rather, the Board identified specific portions of the specification that provided "explicit written description" for claims 11 and 25. Moreover, the Board found the requirement that the capacity to differentiate be the same at the beginning and the end of the culture as "not reasonable" in the context of the disclosure in the '231 patent specification. The Board also rejected the Requestor's arguments (based on the semantics) that because the claim recited "the" capacity to differentiate that this was a specific capacity that must be maintained. The Board was convinced by the specification expressly disclosing stem cells that retained the capacity to differentiate after 15 passages as in Examples 1 and 3.
With regard to the enablement requirement, the Board once again turned to the disclosure of Examples 1 and 3, which the Board asserted "describe suitable culture conditions [to] meet the claim limitations." The Board further rejected "post-filing evidence of unpredictability" that the Requestor asserted in support of its lack-of-enablement contentions. These included a reference that (the Requestor contended) showed loss of differentiation capacity within four passages (Guilak et al., 2006, J. Cell. Physiol. 206: 229-37); the Board discounted this argument because the Guilak authors did not determine differentiation capacity for more than four passages. And the Board's opinion stated that the '231 claims only required one stem cell to retain the differentiative capacity and that determining or identifying this cell did not constitute undue experimentation.
Similarly, the second reference (Safwani et al., 2011, Biotech Applied Biochem. 58: 261-70) did not disclose that its adipose-derived stem cell culture lost all capacity to differentiate after 15 passages, according to the Board (and indeed there was disclosure in the reference that the cells retained osteogenic and neurogenic capacities over all passages reported). The third reference, Zhou et al. (2011, Cells Tiss. Organs 195: 414-27) was misinterpreted by the Requestor according to the Board's opinion, characterizing the Zhou disclosure as merely reciting that differentiation capacity declined with passage number but not that 15 passages were enough to reduce that capacity to zero. Finally, the Board noted that the cited references were directed to tissue engineering, which may impose requirements for sustained capacity to differentiate that are not required by claims 11 or 25 of the '231 patent. Accordingly, the Board reversed the Examiner's final rejection of claims 11 and 25.
The Board also reversed the Examiner's determination not to adopt rejections urged by the Requestor that claims 11, 22, 25, and 28 were inherently anticipated by the disclosure of any of three references (Hauner et al., 1989, J. Clin. Invest. 84: 1663-70; Van et al., 1976, J. Clin. Invest. 58: 699-704; and Zilberfarb et al., 1997, J. Cell Sci. 110: 801-07). The Hauner and Zilberfarb references were applied to claims 1, 3, and 4 (from which claims 11 and 25 depend) and the Hauner, Van, and Zilberfarb references were applied to claims 12, 14, and 15 (from which claims 22 and 28 depend); the Patent Owner did not appeal these rejection of these claims. Thus, the issue before the Board was whether these references also invalidate these dependent claims.
The Board determined that, while the Hauner reference disclosed a method for obtaining adipose tissue derived stem cells that differed from the methods disclosed in the '231 patent, another reference (Winter et al., 2003, Arthrit. Rheumat. 48: 418-29) disclosed that the stem cells obtained according to the method disclosed by the Hauner reference had the capacity to differentiate into cells from "chondrogenic (cartilage), osteogenic (bone) and myogenic (muscle) lineages." The Board concluded that stem cells isolated according to Hauner "were capable of differentiating into at least osteogenic and chondrogenic lineages[], providing sufficient evidence that the[se stem] cells had the same developmental capacity as those claimed which were isolated [according to the methods disclosed in the '231 patent]." The Board then reviewed the application of the Hauner reference to independent claim 6 (from which claim 11 depends) and concluded that the Patent Owner's arguments against the application of Hauner to these claims paralleled the arguments it had rejected when advanced by Requestor (or the Examiner) in support of rejection under § 112(a). That is, the Patent Owner argued that the Hauner reference disclosed loss of the capacity to differentiate with passage in culture of the stem cells obtained using the Hauner methods, and the Board stated that there was no evidence that the Hauner stem cells lost 100% of cells capable of differentiating after passage in culture. Accordingly, as it had determined in assessing Requestor's arguments, the Board found that the claims of the '231 patent at issue required as few as one cell that retained differentiation capacity and the Patent Owner had not established that the Hauner stem cell cultures contained not one cell retaining differentiation capacity after passage in culture.
Finally, the Board applied the specific limitations recited in claims 11, 22, 25, and 28 and found that there was "sufficient evidence" that the Hauner reference met these limitations as well. In this regard the Board used the "plain and ordinary" meaning of the word "isolated," including a dictionary definition (which seems both unnecessary and contrary to the Federal Circuit's AWH v. Phillips decision).
Having found that Examiner incorrectly refused to adopt the Requestor's ground of rejection that the Hauner reference inherently anticipated these claims, the Board did not reach the question with regard to the Van or Zilberfarb references, and remanded to the Examiner for consideration of this new ground of rejection under 41 C.F.R. § 41.77(b). Procedurally, this decision is not final for judicial review, and the Patent Owner can request rehearing or reopen prosecution.
On remand, the Patent Owner is limited to prosecution solely on the new ground imposed by the Board. The Requestor (or the Examiner), on the other hand, can raise new grounds of rejection, but for the Requestor a new ground of rejection must be in response to amendments or new evidence submitted by the Patent Owner. Under these circumstances it is unlikely that the Requestor will attempt or be permitted to introduce arguments related to invalidity under 35 U.S.C. § 101 (as in the WARF stem cell reexamination; see "WARF Stem Cell Patent Claims Rejected in Re-examination").
University of Pittsburgh v. Cellerix (PTAB 2013)
Panel: Administrative Patent Judges Green, Lebovitz, and Guest
Decision on Appeal by Administrative Patent Judge Lebovitz
