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 .
Priority
This application is a continuation of Application No. 18/124346 (filed on 3/21/2023), which is a continuation of Application No. 16/599271 (filed on 10/11/2019), which is a continuation of 15/553115 (filed on 8/23/2017). The latter application is a national stage entry of PCT/EP2016/054640 (filed on 3/04/2016), which claims foreign priority under 35 U.S.C. 119(a)-(d) based on applications AU 2015900777 and AU 2015900752 (filed in Australia on 3/05/2015 and 3/04/2015, respectively).
Certified copies of the foreign priority documents were received in parent application 16/599271.
Drawings
The drawings are objected to because the text and lines in Figure 11 are too small and unclear. 37 C.F.R. 1.84 section (p)(3) requires that “Numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height”, while section (l) states “All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined”. See MPEP § 608.02(V).
Claim Objections
Claim 1 is objected to because of the following informalities: (i) hyphen is missing in between “serum” and “free” in line 1; and (ii) there should be no space or indentation at the beginning of line 5. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claims 2-7, 10-12, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Cancedda et al. (Pub. No. US 6,617,159 B1).
Cancedda et al. provides a serum-free medium for growth and proliferation of mesenychmal stem cells (MSCs) and chondrocytes in culture (Abstract). The serum-free medium can comprise a base minimum essential medium, growth factors like FGF2, steroids, sources of lipids and fatty acids, an iron source (lines 34-48, col. 2).
In Example 1, Cancedda et al. teaches a serum-free medium for expansion of MSCs. It contains 1-10 ng/ml of EGF, PDGF, and FGF-2 (Table 2, col. 4). For instance, each one of these three growth factors can amount to about 5 ng/ml to about 10 ng/ml (lines 21-23, col. 3).
The serum-free medium of Cancedda et al. is comparable to the instant application’s fetal bovine serum free culture medium for the following reasons:
Regarding claim 1: the serum-free medium comprising a base minimum essential medium equivalent to “A fetal bovine serum free cell culture medium comprising: a basal medium”. Given that the prior art uses fetal calf serum as a control (lines 17-20, col. 4), it suggests that the disclosed serum-free medium does not contain a serum like fetal calf serum.
The concentrations of PDGF, FGF-2, and EGF each being 1-10 ng/ml (lines 21-23, col. 3) read on “10 ng/ml or less of platelet derived growth factor (PDGF); 1 ng/ml or less of fibroblast growth factor 2 (FGF2); and 5 ng/ml or less of epidermal growth factor (EGF)”. The courts have held that a prima facie case of obviousness exists when the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP § 2144.05(I) and In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed.Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). In this case, the concentration of each growth factor in the prior art’s serum-free medium overlaps with the claimed concentrations.
The mesenchymal stem cells being grown in the disclosed serum-free medium is analogous to “mesenchymal lineage precursor or stem cells in an undifferentiated state”.
Regarding claims 3-4: the FGF-2 amount being 1-10 ng/ml meets “wherein the level of FGF2 is between 2 pg/ml and 1 ng/ml” and “1 ng/ml”, respectively.
Regarding claim 5: PDGF can be in the form of PDGF-BB (lines 21, col. 4), which corresponds to “wherein the PDGF is PDGF-BB”.
Regarding claims 6-7: the PDGF amount being 1-10 ng/ml satisfies “wherein the level of PDGF-BB is between 3.0 ng/ml and 10 ng/ml” and “10 ng/ml”, respectively.
Regarding claims 10-12: the EGF amount being 1-10 ng/ml fulfills “wherein the level of EGF is between 0.08 ng/ml and 5 ng/ml”, “between 3 ng/ml and 5 ng/ml”, and “5 ng/ml”, respectively.
Regarding claim 16: the mesenchymal stem cells are identical to “wherein the culture medium comprises mesenchymal stem cells”.
Regarding claim 17: the serum-free medium is not explicitly taught to be “xeno-free” as required by the instant claim.
Cancedda et al., however, teaches the various disadvantages of using animal or autologous serum in cell culture (lines 41-56, col. 1). For example, animal or autologous serum are not consistently provided and can vary between batches, expensive, time-consuming, and poses risk of contamination. It would have therefore been obvious to modify the disclosed serum-free medium such that it does not contain any animal or autologous products. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claims 2-7, 10-13, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Cancedda et al. (Pub. No. US 6,617,159 B1) in view of Freshney (Culture of Animal Cells, 6th Edition; John Wiley & Sons, Inc.: Hoboken, NJ, 2010; Chapter 8, pages 99-114).
The teachings of Cancedda et al. are set forth above and applied herein. Cancedda et al. is found to render claims 2-7, 10-12, and 16-17 obvious.
Regarding claim 13: Cancedda et al. only names Coon’s modified Ham’s F-12 medium as a suitable base minimum essential medium and therefore does not meet the requirement “wherein the basal medium is alpha-minimal essential medium”.
Despite this, Freshney shows that alpha-minimal essential medium (αMEM) is a known basal medium for culturing animal cells. Freshney lists αMEM as one of the frequently used media that contain amino acids, vitamins, and other nutrients (Table 8.3, page 102). A person with ordinary skill in the art would have replaced the Coon’s modified Ham’s F-12 medium in Cancedda et al.’s serum-free media and expect that it would still serve as a basal medium that can successfully provide essential nutrients. Obviousness is based on the rationale that simple substitution of one known element for another produces predictable results.
Claim 13 is thus obvious over Cancedda in view of Freshney.
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 2-7, 10-13, and 15-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,685,899.
The U.S. patent is drawn to an in vitro method of cell culture comprising culturing a population of mesenchymal lineage precursor cells or stem cells in a fetal bovine serum free cell culture medium comprising platelet derived growth factor (PDGF), epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), wherein the method increases mesenchymal lineage precursor cell or stem cell proliferation. The cell culture medium can comprise alpha-minimal essential medium.
Although the claims at issue are not identical, they are not patentably distinct from each other because the method employs a fetal bovine serum-free cell culture medium containing components identical to those in the claimed invention: 10 ng/ml or less of PDGF, 5 ng/ml or less of EGF, and 1 ng/ml or less of FGF2. In some embodiments, the PDGF is further limited to PDGF-BB and has a concentration of 10 ng/ml. In other embodiments, the EGF is present in the amount of between 0.08 ng/ml and 5 ng/ml or between 3 ng/mml and 5 ng/ml, while the FGF2 is 1 ng/ml or between 2 pg/ml and 1 ng/ml.
Hence, the U.S. patent’s combination of the serum-free culture medium and mesenchymal lineage precursor cells or stem cells is equivalent to the instant application’s fetal bovine serum-free cell culture medium.
Claims 2-7, 10-13, and 15-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,215,352 in view of Kato et al. (US 2010/0279412 A1).
U.S. 12,215,352 provides a serum-free cell culture medium that is equivalent to the instant application’s fetal bovine serum free cell culture medium. Both media comprise the same components at the same concentrations: a basal medium; 10 ng/ml or less of platelet derived growth factor-BB (PDGF-BB); 1 ng/ml or less of fibroblast growth factor 2 (FGF2); and 5 ng/ml or less of epidermal growth factor (EGF); and mesenchymal lineage precursor cells in an undifferentiated state.
The basal medium can be alpha-minimal essential medium. In various embodiments, the PDGF-BB can amount to 10 ng/ml or 3-10 ng/ml; the concentration of FGF2 can be 1 ng/ml or from 2 pg/ml to 1 ng/ml; and EGF concentration can be 5 ng/ml, from 0.08 ng/ml to 5 ng/ml, or from 3 ng/ml to 5 ng/ml. Moreover, the culture medium can be xeno-free.
The U.S. patent is different from the claims of the instant application in that it is not specified to be “fetal bovine serum free”.
Nonetheless, fetal bovine serum is well-known in the art and routinely used for cell culturing. Kato et al., for example, teaches that culturing of animal cells is generally carried out using a culture medium supplemented with 5-20% of an animal-derived serum such as fetal bovine serum. However, serum is very expensive, requires removal afterwards which makes culturing a complicated process, and poses a risk for pathogen infection (par. [0004]). To address these problems, culture media containing no serum have been developed (par. [0006]).
Since fetal bovine serum is a typically used serum in animal cell culturing as substantiated by Kato et al., it would have been obvious to specifically exclude fetal bovine serum in the U.S. patent’s serum-free cell culture medium.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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, Melenie L. Gordon can be reached at (571) 272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
