DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 5/13/2026 to claims 1, 2, 8, and 48 have been entered. Claims 5-7, 12-29, 31-42, 46, 47, 49, and 50 are canceled. Claims 51 and 52 have been added. Claims 1-4, 8-11, 30, 43-45, 48, 51, and 52 remain pending, and are being considered on their merits. No claims are withdrawn from consideration at this time. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
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.
Claims 1, 3, 4, 8, 10, 11, 30, 44, 45, 48, 51, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Faris et al. (WO 2015/148742), Miyabayashi et al. (US 8,883,504), Miller et al. (US 2004/0122101), Phelps (WO 2017/106783; provided in the ISR dated 9/13/2023), and von Hagen (WO 2018/019812).
Faris teaches a cell culture sustained release composition (Abstract). Faris teaches a tableted composition comprising glucose (a carbohydrate), dibutyl sebacate (a plasticizer), and ethyl cellulose (a binder) (Example 1), reading in-part on claims 1 and 52. Faris teaches further adding amino acids, salts, metals, sugars, lipids, nucleic acids, hormones, vitamins, fatty acids, proteins, buffering salts, or combinations thereof ([0017] and [0063]), reading on claims 1 and 52. Faris teaches CaCl2, KCl, MgCl2, MgSO4, NaCl, NaHCO3, Na2HPO4, and NaH2PO4 H20 ([0066]), reading on those embodiments of salts for claims 1 and 52. Faris teaches amino acids comprising L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cystine, L-cysteine, L-glutamic acid, L-glutamine, glycine; L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L- tryptophan, L-tyrosine, and L-valine ({0064]), reading in-part on claims 1 and 52. Faris teaches vitamin B12 and D2 ([0065]), reading on those embodiments of claims 1 and 52. Faris teaches trace elements comprising copper, nickel, manganese, zinc, chromium, molybdenum, selenium, fluorine/fluoride, and vanadium ([0067]), reading on those embodiments of claims 1 and 52. Faris teaches vitamin B12 and D2 ([0065]), reading on those embodiments of claims 1 and 52. Faris teaches trace elements comprising copper, nickel, manganese, zinc, chromium, molybdenum, selenium, fluorine/fluoride, and vanadium ([0067]), reading on those embodiments of claims 1 and 52. Faris teaches a working example comprising 2 wt% mg stearate (Example 8), reading on claim 1 and 52. Faris teaches that the tableted composition starts to dissolve 30 minutes after placement in a diluent comprising cell culture media (Figure 2 and [0089]), reading on claims 1 and 52. Faris further teaches a tablet comprising sodium bicarbonate particle size of 50 microns or less (10097), reading on the particle size distribution range of claims 1 and 52. Faris teaches a tablet comprising 55% by weight of glucose (Example 8), reading on claim 4. Faris teaches the composition formulated as a powder ([0030]), reading on claim 7. Faris teaches a working example of making the tablets by first preparing an uncoated core tablet by combining D(+) glucose with ethyl cellulose, dibutyl sebacate (a plasticizer), and 1,4-dioxane (a solvent), aliquoting the mixture, and then evaporating the solvent to form tablets (Example 1), then coating the tablets (Example 3), reading in-part on claim 8. Faris teaches a tablet mass of 1.12-5.12 g (Fig. 3 and [0089]), reading on claim 10 and reading in-part on claims 44 and 45. Faris teaches diluting the tablet composition in an Erlenmeyer flask and with (aqueous) DMEM media (Fig.2 and [0089]), reading on the diluent and receptacle of claim 30.
Regarding claim 8, product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See M.P.E.P. § 2113 (III). Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference. In this case, the burden is shifted to Applicant to show that the manufacturing process steps of the product-by-process claim imparts any non-obvious structural characteristics to the claimed product as compared to the substantially similar composition taught by Faris and made by the different method as set forth above.
Regarding claim 11, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. See M.P.E.P. § 2111.02 and 2111.04. In this case, the limitations of claim 11 are only a statement of intended outcome and so the composition of Faris is reasonably construed as being capable of meeting the claim limitations absent any showing to the contrary.
Regarding claims 44 and 45, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, teaches that the tablet mass is result-effective to release more glucose (see Fig. 3), and so any differences between the mass of claimed tablets and the tablets of Faris must be optimization within prior art conditions or through routine experimentation absent any showing of criticality of the claimed range to the contrary.
Regarding claims 1 and 52, it would have been obvious to a person of ordinary skill in the art before the invention was filed to combine the working example of Faris comprising glucose with the exemplary embodiments of Faris comprising amino acids, salts, metals, sugars, lipids, nucleic acids, hormones, vitamins, fatty acids, proteins, buffering salts, or combinations thereof of Faris. A person of ordinary skill in the art would have had a reasonable expectation of success to do so and the skilled artisan would have been motivated to do so because Faris expressly considers the combination; combining prior art elements according to known methods would then predictably yield a tableted composition comprising amino acids, salts, metals, sugars, lipids, nucleic acids, hormones, vitamins, fatty acids, proteins, buffering salts, or combinations thereof as envisioned by Faris. See M.P.E.P. § 2143 (I)(A).
Regarding claims 1 and 52, Faris does not teach a composition comprising 20-40% by mass amino acids, 2-10% by mass of salts, 1-5% by mass of vitamins, 0.01-0.05% by mass of trace elements, 1-5% by mass of vitamins, 35-50% by mass of the embodiment of glucose, and 1-5 percent by mass of croscarmellose sodium. Regarding claims 1 and 52, Faris does not teach a powder with a mean particle size of about 200-320 μm. Regarding claim 30, Faris does not teach a kit. Regarding claim 30, Faris does not teach instructions for use. Regarding claim 48, Faris does not teach any product-by-process limitations to producing the particles by milling. Regarding claim 51 and 52, Faris does not teach a tableted composition capable of providing an auto-pH cell culture medium formulation.
Miyabayashi teaches methods of stem cell culture (Abstract and Col. 1, lines 16-23). Miyabayashi teaches croscarmellose sodium as an exemplary disintegrator and pharmaceutically acceptable carrier (Col. 34, lines 21-27 and lines 39-42), reading in-part on claims 1 and 52.
Miller teaches a pharmaceutical composition comprising croscarmellose sodium and magnesium stearate ([0023]). Miller teaches 5-15% by weight croscarmellose sodium as a disintegrant and 0.1-5% by weight magnesium stearate as a lubricant ([0224]), reading on claims 1 and 52.
Phelps teaches dry cell culture media compositions (Abstract), formulated as tablets (([0069]). Phelps teaches 40% amino acids, 20-65% binders, 1-5% vitamins, 2-10% salts, 0.01-0.05% trace components ([0026]), reading on claims 1 and 52. Phelps teaches calcium, magnesium, and ammonium as exemplary salts and iron, manganese, copper, and zinc as exemplary trace elements ([0023]), reading on claims 1 and 52. Phelps teaches dry cell culture media compositions formulated as a kit in a first container/package and with instructions for use (Abstract; [0033]), and formulated as tablets (([0069]), reading on the kit and package of claim 30. Phelps teaches the dry cell culture media composition further capable of providing an auto-pH cell culture medium formulation (¶0087),reading on claims 51 and 52.
von Hagen teaches methods of improving the solubility or dissolution behavior of components of an aqueous solution (Abstract), such as a cell culture medium (p4, lines 10-29). von Hagen teaches uniform particle sizes less than 500 µm or 200 µm produced by milling (p9, line 27 through p10, line 18; p9, lines 1-3), which are advantageous to better mix poorly soluble components (p9, lines 12-25), wherein the poorly soluble components include leucine, valine, isoleucine, and phenylalanine (p6, lines 7-8), reading on claims 1, 48, and 52. von Hagen teaches formulating dry powder mixtures as tablets (p8, lines 8-19), reading in-part on claims 1 and 52.
Regarding claims 1 and 52, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the croscarmellose sodium of Miyabayashi at the concentration range taught by Miller to the composition of Faris. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Miyabayashi and Faris are directed towards cell culture compositions, and because Miyabayashi, Faris, and Miller are all in-part directed towards solid compositions comprising carriers (binders, disintegrants, etc.) The skilled artisan would have been motivated to do so Faris further teaches dissolving the tablet composition in a diluent, and so the addition would then predictably yield a tablet composition comprising a disintegrator that then facilitates disintegration of the tableted composition when placed into an aqueous solution.
Regarding the croscarmellose sodium concentration of claims 1 and 52, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, Miller teaches that 5-15% by weight of croscarmellose sodium is result effective as a disintegrator, and so any further modification of Miller’s concentration range must be held as optimization within prior art conditions or through routine experimentation absent any showing of criticality of the claimed range to the contrary.
Regarding claims 1 and 52, it would have been obvious to a person of ordinary skill in the art before the invention was filed to formulate the tableted cell culture media composition of Faris according to the ranges of Phelps. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Faris and Phelps are directed towards dry cell culture media compositions formulated as tablets. The skilled artisan would have been motivated to do so because formulation would predictably yield a tableted cell culture media composition at specific concentration ranges for the further culturing of cells as taught by Faris.
Regarding claims 1, 48, and 52, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the dry media particles of Faris with the uniform dry media particles having a size less than 500 microns or less than 200 microns and made by milling of von Hagen in Faris’ dry media tablet composition. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Faris and von Hagen are directed in-part towards dry media tablet composition, and because von Hagen teaches methods of producing the particle size range by milling. The skilled artisan would have been motivated to do so because von Hagen teaches that uniform dry media particles having a size less than 500 microns or less than 200 microns are predictably advantageous to better mix poorly soluble components comprising leucine, valine, isoleucine, and phenylalanine and so would improve solubility of these amino acids in Faris’ dry media tablet composition when said composition is dissolve in an aqueous solution to prepare aqueous media for cell culture. Any further difference in the claimed mean particle range and von Hagen must be held as optimization within prior art conditions or through routine experimentation, absent any showing of criticality to the contrary, for the same reasons given in the preceding sentence citing the known result-effective advantages of von Hagen’s particle size range; see M.P.E.P. § 2144.05.
Regarding claim 30, it would have been obvious to a person of ordinary skill in the art before the invention was filed to combine the tablet composition, diluent, and receptacle of Faris with the first container/package and instructions of Phelps. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Faris and Phelps are directed towards dry and tableted cell culture media compositions. The skilled artisan would have been motivated to do so because the combination would predictably yield packaging for the tablets of Faris and instructions for their downstream use of the composition of Faris. See M.P.E.P. § 2143 (I))(A).
Regarding the auto-pH of claims 51 and 52, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the tableted media composition of Faris to be further capable of providing an auto-pH cell culture medium formulation in view of Phelps. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Faris and Phelps are directed towards dry cell culture media compositions formulated as tablets. The skilled artisan would have been motivated to do so because the addition would predictably improve upon he tableted media composition of Faris to auto-adjust the pH of the media when reconstituted in water.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Faris, Miyabayashi, Miller, Phelps, and von Hagen as applied to claim 1 above, and further in view of Arora (MATER METHODS (2013), 3:175, retrieved from https://web.archive.org/web/20160821192632/http://www.labome.com:80/method/Cell-Culture-Media-A-Review.html ; Reference U).
The teachings of Faris, Miyabayashi, Miller, Phelps, and von Hagen are relied upon as set forth above.
Regarding claim 2, Faris, Miyabayashi, Miller, and Phelps do not teach a product-by-process step wherein the tableted composition is reconstituted to form a base culture medium having an osmolality of about 250-350 mOsm/kg.
Arora teaches that for most cell lines, the optimal osmolarity is about 260-320 mOsm/kg (4th page, subheading “Media Supplements”), reading on claim 2.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the tableted media composition of Faris to an osmolarity of about 260-320 mOsm/kg in view of Arora. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Faris and Arora are directed towards cell culture media compositions. The skilled artisan would have been motivated to do so because Arora teaches that an osmolarity in the range of 260-320 mOsm/kg is a known optimum for most cells lines and so the addition would therefore predictably improve upon the composition of Faris when reconstituted.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 9 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Faris, Miyabayashi, Miller, Phelps, and von Hagen as applied to claim 1 above, and further in view of Natoli et al. (Ch. 33 in Developing Solid Oral Dosage Forms (2017), p917-951) and Verwijs (US 2013/0186801).
The teachings of Faris, Miyabayashi, Miller, Phelps, and von Hagen are relied upon as set forth above.
Regarding claim 9, Faris, Miyabayashi, Miller, Phelps, and von Hagen do not teach a tableted medium having a hardness of about 18-22 kp. Regarding claim 43, Faris, Miyabayashi, Miller, Phelps, and von Hagen do not teach a tableted medium having a hardness of about 10-30 kp.
Natoli teaches methods of compressing pharmaceutical tablets (Introduction on p917), Natoli teaches that the working length of the punches affects the hardness of the tablet (“Tooling Inspection” on p936), reading in-part on claim 9. Natoli teaches exemplary hardness of either 24.4 kp or 36.2 kp with Avicel (an exemplary plasticizer) dependent upon the diameter of the roller used. (Table 33.5 and 33.6), reading in part on claims 9 and 43.
Verwijs teaches a pharmaceutical composition for treating cystic fibrosis (Abstract). Verwijs a tablet composition having a hardness range of 5-20 kp ([0291]), reading on claims 9 and 43. Verwijs further teaches methods of cell culture ([0485]), reading in-part on claims 9 and 43.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the tablets of Faris at 5-20 kp hardness in view of Verwijs and Natoli. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Natoli as a whole teaches detailed methods of formulating tablets and that hardness is results effective to the working length of the punches of the diameter of the roller used, because Verwijs teaches that 5-20 kp hardness was known in this art, and because Verwijs is analogous art being further directed towards methods of cell culture. The skilled artisan would have been motivated to do so because combination would predictably yield a tablet with a hardness range of 5-20 kp; see M.P.E.P. § 2143 (I)(A).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 6-9 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
On page 7 of the reply, Applicant traverses the teachings of von Hagen as previously applied to canceled claims 46 and 47 and now applied to claims 1 and 52 in view of the instant amendments. Applicant’s arguments appear to be predicated that von Hagen does not teach every element of claim 1 as amended and new claim 52. This is not found persuasive of error, as von Hagen is not applied alone, but in combination with Faris, Miyabayashi, Miller, and Phelps, and the claimed invention becomes obvious when the references are considered together as a whole rather than each alone. Similarly, Applicant’s arguments are not persuasive over the new grounds of rejection over von Hagen in that criticality of the claimed range has not yet been shown; see M.P.E.P. § 2144.05.
. Applicant’s remaining arguments on pages 7-9 of the reply are not found persuasive over the modified/new grounds of rejection set forth above. Briefly restated, Phelps teaches dry cell culture media capable of auto-adjusting the pH when reconstituted as set forth in new claims 51 and 52.
Conclusion
No claims are allowed. No claims are free of the art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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, Sharmila Landau can be reached at 571-272-0614. 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.
/Sean C. Barron/Primary Examiner, Art Unit 1653
Prosecution Insights