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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Status
Applicant’s arguments and amendments dated 3/15/26 have been received and entered in the application.
Claims 1, 3-8, 10-13, 15-16, 19, 22, 24-28 are currently pending and examined on the merits.
Claims 1, 27 are currently amended.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections rejections not specifically reiterated are hereby withdrawn.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3-8, 11, 13, 24-25, and 27-28 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Katz et al., US Publication No. 2008/0248003 (hereinafter Katz).
Regarding claims 1, 27-28, Katz teaches methods and compositions for enhancing growth and differentiation of adipose tissue-derived stromal cells (ASCs) (Abstract). Katz discloses that the ASCs are cultured attach to uncoated plates without difficulty (i.e., they are adherent) (Abstract; 0152).
Regarding claim 1(a), 3-6, and 27-28, Katz teaches culturing human ASCs in low serum media (AR8- 0.5% human serum) or in serum-free media (AR8 sf), both comprising bFGF (FGF-2), EGF, PDGF, and TGF-β in some embodiments (0237; Tables 1 and 2). AR8 media is supplemented with ITS+3 (mixture of insulin, transferrin and sodium selenite (0237; claim 12; 0021).
Regarding claim 1(b), 10, and 27-28, Katz teaches, after culturing in a first culture medium, replating the cells in AR8 with 0.5% human serum, and then switching half of the cells to serum-free AR8 (second medium), which comprises activating components such as EGF and IL-1 (0233-0237, 0254, Table 1).
Regarding claim 7, Katz teaches including dexamethasone in the AR8 base recipe (medium for low serum and serum-free culture) (see Table 2- 0255; 0257).
Regarding claim 8, Katz teaches growing the cells in the first medium comprising 0.5% human serum for 30.50 ± 3.04 population doublings (Table 3- 0260).
Regarding claims 11 and 28, the second medium comprises EGF in some embodiments (0237; Tables 1 and 2).
Regarding claim 13, Katz’s cells originate from adipose tissue (0014; 0055).
Regarding claim 24, Katz teaches pharmaceutical compositions comprising the adipose tissue-derived stem cells (0161).
Regarding claim 25, Katz teaches that the composition comprising the cells can be cultured in a bioreactor (0174).
Therefore, every limitation of claims 1, 3-8, 11, 13, 24-25, and 27-28 is present in Katz and the subject matter is anticipated.
Claim Rejections - 35 USC § 102/103
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 15-16, 19, 22 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Katz as applied to claims 1, 3-8, 11, 13, 24-25, and 27-28 above.
Regarding claim 15, Katz is silent as to positive expression of CD73, CD90, CD29, and CD105. Regarding claim 16, Katz is silent as to negative expression of CD3, CD4, and CD39. Regarding claim 19, Katz is silent as to positive expression of CD141. Regarding claim 22, Katz is silent as to negative expression CD3, CD4, CD11b, CD14, and CD19.
Regarding claims 15-16, 19, 22, the claims each contain a wherein clause that recites the intended result of the method rather than requiring an additional, active method step be performed. MPEP § 2111.04 states “[c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since these claims only recite the results of the actively recited method steps (resultant marker expression pattern), art reading on the method of claim 1, necessarily results in the same expression profile in the absence of evidence to the contrary including unexpected results.
Further, the Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not the expanded ASCs of the prior art differ, and if so to what extent, from applicant’s ASCs. The prior art discloses ASCs which is similar to applicant’s ASC for these reasons: Katz discloses a method of expanding a population of adipose-derived adherent by culturing in a first medium containing less than 5% animal serum, and culturing in a second medium containing less than 5% animal serum and an activating component. Where an examiner cannot determine whether or not the reference inherently possesses properties which anticipate, or render obvious, the claimed invention a rejection under §§102/103 is appropriate. See MPEP §§ 2112-2112.02.
The cited art taken as a whole demonstrates a reasonable probability that the resultant ASC population of Katz is either identical or sufficiently similar to the claimed ASC population that whatever differences exist, they are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants. See MPEP § 2112(v). Clear evidence that ASCs of the cited prior art does not possess a critical characteristic that is possessed by the claimed ASCs would advance prosecution and might permit allowance of claims to applicant’s method. Applicant is requested to specifically point out the support for any amendments made to the disclosure and arguments in response to this Office Action, including the claims. See MPEP §§ 714.02 and 2163.06. Applicant is also requested to refer to pages and line numbers in the as-filed specification. It is noted that other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Katz as applied to claims 1, 3-8, 11, 13, 24-25, and 27-28 above, and further in view of Prather et al. (Cytotherapy, 2009).
Regarding claim 12, Katz does not disclose that the cells originate from placenta tissue.
Prather compares the characteristics of placental-derived adherent stromal cells with bone marrow- and adipose-derived mesenchymal stem cells (see pg. 427, left col., par. 2). Prather discloses that placental-derived ASC may provide off-the-shelf supply of therapeutic cells that may potentially be less expensive and more convenient than bone marrow or adipose-derived MSC.
Regarding claim 26, Katz does not disclose expanding the population of ASC in a bioreactor comprising a synthetic 3D growth substrate.
Prather teaches expanding the placenta-derived adherent stromal cells in bioreactors, seeded onto carriers (3D growth substrate) (abstract; pg. 428, right col., par. 3).
Accordingly, it would have been obvious to a person of ordinary skill in the art to perform a method of culturing adherent stromal cells by using placental-derived stromal cells since placental derived adherent stromal cells were obtained and known in the art before the effective time of filing, similar to stromal cells from other sources such as bone marrow and adipose tissue, which were also well-known in the art. Thus, one of ordinary skill in the art would have been motivated to combine Katz’s method of expanding adipose derived stromal cells with Prather’s disclosure of placenta-derived adherent stromal cells with the purpose of evaluating the expansion potential of cells originated from different sources for possible clinical applications. Moreover, a skilled artisan would have had a reasonable expectation of success since placenta-derived stromal cells were known and used before the effective time of filing and were disclosed by Prather as being potentially less expensive than bone marrow or adipose-derived MSC.
Similarly, it would have been obvious to expand the population of ASC in a bioreactor comprising a synthetic 3D growth substrate, since ASC have been successfully cultured in bioreactors comprising carriers as taught by Prather. One of ordinary skill would have been motivated to expand the population of ASC in a bioreactor comprising a synthetic 3D growth substrate to provide a 3D microenvironment than enables the large-scale growth of the cells, as taught by Prather.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 3/15/26 have been fully considered but they are not persuasive.
Claim(s) 1, 3-8, 11, 13, 24-25, and 27-28 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Katz.
Applicant argues that the claimed method requires two distinct culture phases (Response p9, 11-13). Applicant argues that Katz does not disclose a deliberate stepwise expansion method in which the first culture media differs from the second, or that the first phase produces a defined first expanded population; that Katz describes routine culturing conditions (Response p9, 11-13). Applicant argues that the act of replating in Katz refers to routine passaging of adherent cells, which does not involve the creation of a defined intermediate population of cells (Response p9-10, 11-13).
In response, the claims as presented do not appear to include any additional steps beyond those of routine tissue culture expansion. Nothing in the claims differentiates the harvesting and isolation of the present method (e.g., selecting based on surface marker expression such as FACS, density gradient centrifugation, microfluidic cell separation, etc.). The claims as presented merely require incubating, separating (i.e., collecting) cells, and transferring to a different culture media, the same steps as a routine expansion.
Applicant argues that Katz fails to disclose that the second culture media differs from the first culture media (Response p10-13).
The claims merely require that the “second media differs in composition”. The claims do not require that the basal media be different in composition; the media as a whole (i.e., basal plus supplements) differs in some respect. Therefore, under a broadest reasonable interpretation, any component which is different in either quantity or as to it’s inclusion qualifies as a difference. Katz discloses that the first media contains 0.5% serum, while the second media is serum-free. This qualifies as a difference between the media, and reads on the claims as presented.
Applicant argues that Katz merely discloses the addition of factors such as VEGF and TGF-β in experimental sections to test the behavior of ASCs; they are not directed to using the factors as activating components (Response p 11-13).
References are considered relevant as prior art for all they contain, including nonpreferred and alternative embodiments. See MPEP § 2123. Further, it is not necessary that the prior art suggest the same advantage or rationale as applicants. See MPEP § 2144. Katz discloses culturing expanded ASCs in a second media different than the first, wherein the second media contains at least one “activating component[s]”. Therefore, Katz reads on the claims as presented.
Applicant argues that routine passaging does not necessarily involve separating a defined expanded population from a first media, and transferring to a second media that differs from the first (Response 11-14).
In response, solely for the purposes of responding to applicant’s arguments, R. Ian Freshney, “Subculture and Cell Lines.” In: Culture of Animal Cell: A Manual of Basic Technique and Specialized Applications. (Hoboken, NJ, John Wiley & Sons, Inc., 2010), pp. 187-206. QH585.2.F74 2010. (hereinafter Freshney) discloses standard subculture techniques including removing existing media, typsinizing, isolating, counting, and re-seeding in new media (12.4, Protocol 12.3). Without additional steps, applicant’s method appears to read directly on standard subculture techniques. Additionally, Katz discloses changing the media type during subculture.
Applicant argues that the structural feature of a compositionally distinct second media, and a functional requirement of activating components are absent in Katz (Response p14).
In response, the examiner disagrees for the reasons set forth supra.
Claim(s) 15-16, 19, 22 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Katz. Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Katz as applied to claims 1, 3-8, 11, 13, 24-25, and 27-28 above, and further in view of Prather.
Applicant argues that Prather cannot remedy the deficiencies noted in Katz (Response p15).
As noted above, the examiner disagrees that Katz fails to read on the claims as presented for the reasons set forth supra.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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