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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 16 June 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 16 June 2026.
CLAIMS UNDER EXAMINATION
Claims 8-9 and 14-25 have been examined on their merits.
PRIORITY
Foreign Priority document EP19168683.1 filed on 11 April 2019 is acknowledged.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
REJECTIONS
New grounds of rejection have been necessitated by claim amendment.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-9 and 14-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 has been amended to recite the cell culture medium is “…a dry and granulated”. It is unclear if the claim means the cell culture medium is dry and granulated. Appropriate correction is required. All dependent claims are included in this rejection.
Regarding claims 14-19 and 22-24: There is a lack of antecedent basis for “the dry and granulated cell culture medium”. Appropriate correction is required. All dependent claims are included in this rejection.
Claim 14 (line 4) recites a “dry, granulated cell culture medium”. The phrase lacks antecedent basis in claim 8. Appropriate correction Is required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 8-9, 14 and 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Fike et al. (Dry powder cell culture products and methods of production thereof. US20130109094A1) in view of Jones et al. (previously cited; Isolation of Mutants Lacking Branched-Chain Amino Acid Transaminase. Somatic Cell Genetics, Vol. 2, NO. 3, 1976 pages 235-243)
Fike teaches a dry, media supplement powder ([0030] [0038] [0141]). The media supplement can include amino acids and variants thereof ([0033] [0184]). The art teaches a dry media supplement comprising at least one amino acid and at least one vitamin ([0303]). The art teaches at least one amino acid, including valine ([0247]).
The art teaches a feed is a supplement used to replace exhausted or diminished media components ([0022] [0265] [0269]). Feed supplement is in a dry powder form ([0271]). The feed supplement reconstituted prior to the feeding ([0271]). The art teaches reconstitution in a solvent, preferably water ([0302] [0307]). CHO cells can be cultivated ([0041] [0260]).
The art teaches CHO cells are grown in a fed batch process ([0136]-[0139] [0710]). CHO cells are seeded in a 1 L bioreactor with a 700 ml working volume ([0710]). The fluid the cells are in is interpreted to be an aqueous basal medium. The art teaches fed-batch culture comprising feeding on days 4, 7 and 10 with a feed supplement medium ([0710]). Therefore the art teaches feeding several times.
While Fike teaches valine, the art does not teach culturing with α-ketoisovaleric acid.
Jones et al. culture wild-type CHO cells in a culture medium containing either valine or α-ketoisovlareic acid (10-4 M) (second paragraph of Results section on page 237; Figure 1; Table 1; see page 237, third paragraph). Jones also teaches wild type CHO cells can utilize the α-ketoacids corresponding to leucine and isoleucine (page 241, second paragraph).
Jones teaches the first step in the catabolism of certain amino acids is a transamination resulting in the formation of the corresponding a-keto acid. This reaction is reversible, and the a-keto acids can substitute for particular amino acids in supporting growth of mammalian cells in culture (page 235, first paragraph).
It would have been obvious to substitute α-ketoisovlareic acid for valine in the medium taught by Fike. See KSR B, which teaches that it is rational to substitute one known, equivalent element for another to obtain predictable results. Substitution of α-ketoisovlareic for valine for CHO cell culture is taught in the prior art. In the instant case, Fike cultures CHO cells and Jones teaches valine can be provided as α-ketoisovlareic acid in a culture medium for CHO cells. One would have had a reasonable expectation of success since Jones explicitly teaches CHO cells can be cultured in medium in which valine is substituted with α-ketoisovlareic acid. One would have expected similar results since Fike and Jones both teach methods of culturing CHO cells. Fike teaches a supplement comprising at least one amino acid and at least one vitamin. Therefore a feed comprising α-ketoisovlareic acid and a vitamin would read on the “consisting of” language recited in claim 8. Therefore claim 8 is rendered obvious.
Fike teaches a concentrated feed medium. The skilled artisan would optimize the amount of α-ketoisovlareic acid taught by Jones based on the desired concentration See MPEP 2144.05. One would have expected similar results combining the references since Fike and Jones are each directed to media for culturing mammalian cells. Therefore claim 9 is included in this rejection. The concentrations recited in claims 14 and 18-19 are rejected on the same grounds.
Fike teaches a pH of 7.1-7.5 ([0180]) Therefore claims 20-21 are included in this rejection
Fike teaches .36 -1.8 g/L or 26.699 g/kg valine based on the concentrations of the feed medium ([0517] [0702). Therefore claim 22 is included in this rejection.
Fike teaches the dry powder media will have sieve analysis characteristics wherein from 51% to 99% of the particles by mass are within the 30 to 200 mesh range ([0226]). Therefore claim 23 is included in this rejection.
The media taught by Fike does not contain NAD. Therefore claim 24 is included in this rejection.
Regarding independent claim 25: The claim encompasses more than one saccharide, amino acid, vitamin, vitamin precursor, salt , buffer, co-factor or nucleic acid.
The teachings of Fike are reiterated.
While Fike teaches valine, the art does not teach culturing with α-ketoisovaleric acid.
The teachings of Jones are reiterated.
It would have been obvious to substitute α-ketoisovlareic acid for valine in the medium taught by Fike. See KSR B, which teaches that it is rational to substitute one known, equivalent element for another to obtain predictable results. Substitution of α-ketoisovlareic for valine for CHO cell culture is taught in the prior art. In the instant case, Fike cultures CHO cells and Jones teaches valine can be provided as α-ketoisovlareic acid in a culture medium for CHO cells. One would have had a reasonable expectation of success since Jones explicitly teaches CHO cells can be cultured in medium in which valine is substituted with α-ketoisovlareic acid. One would have expected similar results since Fike and Jones both teach methods of culturing CHO cells. Fike teaches a supplement comprising at least one amino acid and at least one vitamin. Therefore a feed comprising α-ketoisovaleric acid and a vitamin would read on the “consisting of” language recited in claim 25. Therefore claim 25 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Fike in view of Jones et al. as set forth in the rejection of claim 8 above, and further in view of Eagle et al. (previously cited; Amino Acid Metabolism in Mammalian Cell Cultures. Science. Volume 30 pages 432-437).
Claim 8 is rejected on the grounds set forth above. The teachings of Fike and Jones are reiterated. It is also noted Jones teaches wild type CHO cells can utilize the α-ketoacids corresponding to leucine and isoleucine (page 241, second paragraph). Neither reference teaches a medium which does not contain isoleucine, leucine, valine, phenylalanine or methionine.
Eagle teaches a minimum essential medium for cultivation of mammalian cells (Table 1). The medium contains L-amino acids, carbohydrate, salts and vitamins. The art teaches the essential amino acids L-valine, L-methionine and L-isoleucine can be replaced by their keto acid analogs (α-ketoisovaleric, α-keto-γ-methiobutyric and α-keto-β-methylvaleric, respectively) in mammalian cell cultures (see Table 2).
It would have been obvious to substitute isoleucine, leucine, valine, phenylanalnine and methionine with the corresponding keto acid analogs in the culture medium taught by Fike. See KSR B, which teaches it is rational to substitute one known, equivalent element for another to obtain predictable results. Substitution of the claimed amino acids with their α-keto analog is taught in the prior art. In the instant case, Fike cultures mammalian cells and Jones and Eagle teach amino acids can be substituted with the α-keto analogs when culturing mammalian cells. One would have expected similar results since Fike and Jones both teach methods of culturing CHO cells. Therefore claim 15 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Fike as in view of Jones et al. as set forth in the rejection of claim 8 above, and further in view of Meister et al. (previously cited; Enzymatic Preparation of α-keto acids. J Biol Chem. 1952 May;197(1):309-17).
Claim 8 is rejected on the grounds set forth above. The teachings of Fike and Jones are reiterated.
Jones is silent regarding a sodium salt of α-ketoisovalerate (claims 16 and 17).
Meister teaches a method of making keto acids and sodium and barium salts of keto acids (page 309, first paragraph). The art explicitly teaches sodium a-ketoisovalerate (page 312, section (l); see Table 1). Meister teaches sodium salts are prepared as crystals (page 13, first paragraph of summary).
It would have been obvious to try using the sodium salt of α-ketoisovalerate in the system taught by Fike. One would have been motivated to do so since Fike teaches α-ketoisovalerate and Meister teaches a-Ketoisovalerate is available as a sodium salt. One would have had a reasonable expectation of success since Meister teaches α-Ketoisovalerate can be prepared as a sodium salt. One would have expected similar results since Meister teaches α-Ketoisovalerate and its sodium salt have similar activity. Therefore claims 16-17 are included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 16 June 2026 are acknowledged.
Argument 1: The Applicant argues claim 8 recites a cell culture medium “consisting of” the claimed components. The Applicant argues Fike as a whole shows that valine is a part of the concentrated feed supplement medium. The Applicant argues there is no reason for substituting valine for the claimed keto acid.
Response: Fike teaches a supplement comprising an amino acid and a vitamin. Fike teaches variants of an amino acid can be used. Substitution if valine for its keto-acid is rendered obvious on the grounds set forth above. A supplement comprising α-ketoisovaleric acid and a vitamin would read on the “consisting of” language recited in the claims.
As set forth above, a substituting valine for its keto acid. The prior art teaches substituting valine with its keto acid to culture CHO cells. The substitution of one known element for another yields predictable results to one of ordinary skill in the art. See KSR B. While Fike is silent regarding keto acids, the art teaches the use of amino acids or their variants. Fike cultures CHO cells and Jones teaches CHO cells can be cultured with α-ketoisovaleric acid as a substitute for valine.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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