Pachmann, Ulrich et al.Download PDFPatent Trials and Appeals BoardNov 6, 20202020002647 (P.T.A.B. Nov. 6, 2020) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 14/419,149 05/29/2015 Ulrich PACHMANN 6460-0113PUS1 1940 2292 7590 11/06/2020 BIRCH STEWART KOLASCH & BIRCH, LLP 8110 Gatehouse Road Suite 100 East Falls Church, VA 22042-1248 EXAMINER KIM, TAEYOON ART UNIT PAPER NUMBER 1632 NOTIFICATION DATE DELIVERY MODE 11/06/2020 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): mailroom@bskb.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ULRICH PACHMANN and KATHARINA PACHMANN __________ Appeal 2020-002647 Application 14/419,149 Technology Center 1600 __________ Before JEFFREY N. FREDMAN, JOHN G. NEW, and MICHAEL A. VALEK, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a method of testing sensitivity of tumor cells or a therapeutic measure for treating a tumor disease. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as the Applicant, Ulrich Pachmann and Katharina Pachmann (see Appeal Br. 1). 2 We have considered the Specification of May 29, 2015 (“Spec.”); Final Office Action of Jan. 8, 2019 (“Final Act.”); Appeal Brief of Oct. 3, 2019 (“Appeal Br.”); and Examiner’s Answer of Dec. 16, 2019 (“Ans.”). Appeal 2020-002647 Application 14/419,149 2 Statement of the Case Background “The invention provides a method for culturing a subpopulation of circulating epithelial tumor cells from a body fluid from a human or animal, more particularly a mammal, affected by an epithelial tumor” (Spec. 3:8– 11). “The response of the circulating tumor cells to a therapy correlates strongly with a relapse-free survival” (id. at 5:10–12). The Claims Claims 8–12 and 19 are on appeal. Claim 8 is the sole independent claim, is representative and reads as follows: 8. A method of testing sensitivity of tumor cells with respect to a medicament or a therapeutic measure for treating a tumor disease underlying the occurrence of circulating epithelial tumor cells in a human or animal, comprising: (i) separating cells present in a body fluid from the human or the animal and containing at least one nucleus in each case from the body fluid without selection of certain of these cells; (ii) transferring said separated cells to a cell culture medium; (iii) culturing said transferred separated cells under cell culture conditions in said cell culture medium containing at least an animal serum, a growth stimulator and one growth factor, wherein the growth stimulator is insulin and hydrocortisone and wherein the growth factor is Epidermal growth factor, and wherein the cells are cultured for at least 24 hours in suspension at least until a subpopulation of tumor cells, which does not require adherence to a surface for proliferation, has formed spheroids by proliferation, and wherein tumor cells which have formed the spheroids during culturing are separated from the cultured tumor cells, by separating the spheroids formed during culture; and Appeal 2020-002647 Application 14/419,149 3 (iv) testing of sensitivity of tumor cells in the spheroids obtained in step (iii) with respect to the medicament or the therapeutic measure by exposing the spheroids obtained in step (iii) to the medicament or the therapeutic measure and analyzing the effect of the exposure. The Rejection3 The Examiner rejected claims 8–12 and 19 under U.S.C. § 103(a) as obvious over Goodman,4 Kawabe,5 Friedrich,6 Vinci,7 Marrinucci,8 and Wu9 (Final Act. 3–7). The Examiner finds Goodman teaches screening CTCs (circulating tumor cells) for drug sensitivity (Final Act. 5) by obtaining cells without separation, and growing the cells in a culture medium for at least 24 hours to form spheroids (id. at 3–4). The Examiner finds Goodman teaches both serum free and serum containing media (id. at 3). The Examiner finds Marrinucci evidences that CTCs can originate from non-small lung cancer 3 We note that the Examiner has acknowledged that Marchetti et al., US 2014/0322356 A1, published Oct. 30, 2014, is not prior art to the instant application (see, e.g., Ans. 3). 4 Goodman et al., US 2013/0078667 A1, published Mar. 28, 2013. 5 Kawabe et al., US 2006/0014157 A1, published Jan. 19, 2006. 6 Friedrich et al., Spheroid-based drug screen: considerations and practical approach, 4 Nature Protocols 309–24 (2009). 7 Vinci et al., Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation, 2012 BMC Biology 10–29 (2012). 8 Marrinuchi et al., Circulating Tumor Cells From Well-Differentiated Lung Adenocarcinoma Retain Cytomorphologic Features of Primary Tumor Type, 133 Arch Pathol Lab Med 1468–71 (2009). 9 Wu, R., Growth of Human Lung Tumor Cells in Culture, in Culture of Human Tumor Cells 1–21 (Pfragner and Freshney, Eds., Wiley-Liss, Inc.) (2004). Appeal 2020-002647 Application 14/419,149 4 (id. at 4). The Examiner acknowledges that Goodman does not suggest the use of hydrocortisone and insulin in the growth media for CTCs (see Final Act. 4). The Examiner finds that “Wu teaches that insulin, hydrocortisone and EGF are principal supplements in the medium for culturing lung cancer cells” (Final Act. 4). The Examiner finds it obvious that “one skilled in the art would consider insulin, hydrocortisone and EGF as supplements for the culture medium for non-small cell lung cancer cells, and would utilize them for CTCs of NSCLC origin” (id.). The Examiner relies upon Kawabe, Friedrich, and Vinci to show that spheroids may be used for drug screening and for elements of the dependent claims (see, e.g., id. at 5–6). The issue with respect to this rejection is: Does a preponderance of the evidence of record support the Examiner’s conclusion that Wu does not teach away from the use of serum containing medium? Findings of Fact 1. Goodman teaches, regarding the preamble and step (iv), that “applications for using the isolated and expanded CTCs include . . . drug sensitivity testing . . . and treatment response assessment” (Goodman ¶ 60). 2. Goodman teaches, regarding step (i), that “the sample can be processed to remove or reduce the number of non-CTC in the sample (i.e., to enrich for CTC) and the resulting cell population that contains CTC can be cultured in accordance with the methods described herein. Alternatively, the sample can be cultured without further processing” (Goodman ¶ 28). Appeal 2020-002647 Application 14/419,149 5 3. Goodman teaches, regarding step (ii), that: Many suitable media formulations are well known and conventional in the art, such as RPMI media, Knockout serum replacement media, F12K, and DMEM. The culture media is preferably supplemented with a low concentration of serum, plasma or growth factors (i.e. 5% or less (v/v) serum or plasma) or is serum or plasma free. (Goodman ¶ 33). 4. Goodman teaches, regarding step (iii), an example of culturing to form spheroids: Culturing of the CTCs in spheroid forming culture media: Once the buffy coat cells containing the CTCs were ready the media was freshly reconstituted by mixing 0.5 μ1 human EGF (200 μg/ml), 100 μl of knockout serum and 5 ml of DMEM/F12 working media. The working media contained DMEM/F 12 media base with 5 ml non essential amino acid, and 0.5 ml BME (100 μM stock in PBS) and 5 ml of penicillin/ streptomycin. . . . The growth of the CTCs was monitored for 14 days before they were passaged to fresh media. (Goodman ¶ 70). 5. Wu teaches “We, as well as other researchers, initially used a serum-supplemented medium to establish primary cultures of normal specimens and lung tumor specimens. These attempts have proven to be unsuccessful” (Wu 3). 6. Wu teaches their laboratory was The first to develop a serum-free, hormone-supplemented medium for primary human airway epithelial cell growth and long-term maintenance in culture. The principal supplements in this medium are insulin, transferrin, hydrocortisone, epidermal growth factor (EGF), retinoid, and a supplement essential for cyclic adenosine monophosphate (cAMP) generation. (Wu 3). Appeal 2020-002647 Application 14/419,149 6 7. Wu teaches, regarding non-small cell lung cancer (“NSCLC”) cell culturing, that “phenotypic differences among different tumor cells required different culture media and growth supplements” (Wu 4). 8. Wu teaches, in Protocol 1.4, that to obtain floating aggregates, use a “serum-free, HITES-based medium” (Wu 13). Principles of Law “A reference may be said to teach away when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). Analysis Appellant contends “Wu teaches away from initially using a medium containing an animal serum in conjunction with insulin, hydrocortisone and EGF for the culture of floating cells, which do not require adherence to a surface for proliferation and for initiating formation of spheroids” (Appeal Br. 7). Appellant contends that Wu teaches According to Protocol 1.4, step (b), the cells are cultured without serum for 1 to 2 weeks. Under these conditions most SCLC cells grow as floating aggregates, whereas normal cells will attach to the dish to proliferate. Thus, it is easy to recognize that the primary culture has SCLC cells. According to Protocol 1.5, Adenocarcinoma and Large Cell Carcinoma Cells (which are equivalent to NSCLCs, see Wu, page 2, next to last sentence of next to last paragraph) adhere to the surface of the flask during culturing. (Appeal Br. 7). The Examiner acknowledges that “it is understood that the steps (a)- (d) of Wu in p. 13 are carried out in the absence of serum for establishing Appeal 2020-002647 Application 14/419,149 7 primary lung cancer cell culture (SCLC)” (Ans. 8). The Examiner contends that “Goodman teaches the use of serum for suspension culture of CTCs (see paras. 33-34)” (id.). “Thus, it is the Examiner’s position that teachings of Marchetti and/or Wu are not sufficient to be considered as evidence teaching away the use of serum for CTC suspension culture, when Wu as well as Goodman teaches that serum can be used for CTC suspension culture” (id.). We find that Appellant has the better position. Whether Wu or Goodman generally teach that serum has been used for culturing CTC cells does not address the specific teaching by Wu that “[w]e, as well as other researchers, initially used a serum-supplemented medium to establish primary cultures of normal specimens and lung tumor specimens. These attempts have proven to be unsuccessful” (FF 5). Wu teaches, instead, the use of serum-free media (FF 6). Wu teaches that different cells require different media (FF 7) and teaches to use serum-free media to get floating aggregates such as spheroids (FF 8). Thus, we agree with Appellant that Wu would discourage the use of medium containing serum for growth of this cell population into spheroids and therefore teaches away from the recitation in claim 1 to use a “cell culture medium containing at least an animal serum.” The Examiner’s reliance on Goodman does not persuade us differently. Goodman only generically teaches serum or serum free media (FF 3), but in Goodman’s only example of growing spheroid cells, Goodman uses serum-free medium (FF 4). Thus, Goodman does not address or cure Wu’s teaching away. Marchetti is not prior art, so the Examiner’s continued reliance on this reference does not properly address the rejection. The other cited references also do not address this issue. Appeal 2020-002647 Application 14/419,149 8 Conclusion of Law A preponderance of the evidence of record does not support the Examiner’s conclusion of obviousness. SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 8–12, 19 103 Goodman, Kawabe, Friedrich, Vinci, Marrinucci, Wu 8–12, 19 REVERSED Copy with citationCopy as parenthetical citation