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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 13 February 2026.
CLAIMS UNDER EXAMINATION
Claims 1-4 and 6-25 are pending. 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WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.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 “wherein the cell culture medium is dry powder or dry, granulated”. It is unclear what “dry, granulated” means. 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, granulated cell culture medium”. Appropriate correction is required. All dependent claims are included in this rejection.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 25 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 25: Base claim 8 recites “a saccharide”, “amino acid”, “a vitamin”, “a salt”, “an antioxidant”, “a chelator”, “a growth factor”, “a buffer”, “a co-factor”, “a nucleic acid” and “a hormone” are each a component. The claim recites one or more components can be selected.
Claim 25 is not further limiting because “one or more amino acids” does not further limit “an amino acid”. “One or more saccharide components” does not further limit “a saccharide”. “One or more salts” does not further limit “a salt”. “One or more buffer components” does not further limit “a buffer”. “One or more nucleic acid components” does not further limit “a nucleic acid”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 and 20-25 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) as evidenced by Rudman et al. (Capacity of human subjects to utilize keto analogues of valine and phenylalanine (J. Clin. Invest. 1971; 50(1):90-96) and Merriam Webster Dictionary (definition of derivative).
Fike teaches a powder (i.e. dry) media for cell culture (Abstract; [0041]). The media contains all of the necessary factors for in vitro cultivation (Abstract). CHO cells are cultured ([0041]). 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.
Feed supplements (hence, feed medias) are utilized to supplement a medium that has or is being used to culture cells. As the cells are cultured, some ingredients are removed from the medium by the cells. The feed supplement is used to replace some or all ingredients ([0269]). Feed supplement is in a dry powder form ([0271]). The feed supplement is typically reconstituted prior to the feeding ([0271]). The art teaches reconstitution in a solvent, preferably water ([0302] [0307]). The art teaches a 5x concentrated feed containing valine and riboflavin (a vitamin) ([0705]]).
Claim 8 recites “alpha-ketoisovaleric acid” and derivatives thereof. The specification does not define the term “derivative”. As evidenced by Rudman et al., valine is a keto analogue of α-ketoisovaleric acid (see Abstract). As evidenced by Merriam Webster Dictionary derivative is broadly interpreted to be “a chemical substance related structurally to another substance”. Therefore valine is interpreted to read on at least one alpha keto acid as recited in claim 8.
The art does not teach the claim limitations with sufficient specificity to anticipate claim 8.
It would have been obvious to culture CHO cells in a fed batch culture using a feed media consisting of valine and a vitamin. One would have been motivated to do so since Fike teaches fed batch culture of CHO cells and teaches a feed media comprising amino acids and vitamins. One would have had a reasonable expectation of success since Fike teaches the composition can be used as a feed media for CHO cells. Therefore claim 8 is rendered obvious.
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.
The art teaches valine (a derivative of alpha-ketoisovaleric acid) and vitamins (supra). Therefore claim 25 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 9, 14-15 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fike as evidenced by Rudman as applied to claim 8 above, in view of Eagle et al. (Amino Acid Metabolism in Mammalian Cell Cultures. Science. Volume 30 pages 432-437) and Jones et al. (Isolation of Mutants Lacking Branched-Chain Amino Acid Transaminase. Somatic Cell Genetics, Vol. 2, NO. 3, 1976 pages 235-243)
Claim 8 is rejected on the grounds set forth above. The teachings of Fike are reiterated. Fike teaches a derivative of α-ketoisovaleric acid (valine) in a cell culture media.
The art does not teach adding α-ketoisovaleric acid.
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 some of the amino acids can be replaced by immediate precursors as the corresponding keto acids (see text below Table 1). The art teaches this substitution relates to the form in which the amino acid may be supplied (see text below Table 1). 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).
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). It is also noted Jones teaches wild type CHO cells can utilize the α-ketoacids corresponding to leucine and isoleucine (page 241, second paragraph).
It would have been obvious to substitute α-ketoisovlareic acid for valine in a medium to for culturing CHO cells. KSR B teaches that it is rational to substitute one known, equivalent element for another to obtain predictable results. In the instant case, Eagle teaches valine can be provided as α-ketoisovlareic acid in a culture medium for mammalian cells. One would have had a reasonable expectation of success since Eagle teaches amino acids can be provided as their keto acid analogs in a minimal essential media and Jones explicitly teaches CHO cells can successfully be cultured in medium in which valine is substituted with α-ketoisovlareic acid. 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, Eagle and Jones are each directed to media for culturing mammalian cells. Therefore claim 9 is rendered obvious. The concentrations recited in claims 14 and 18-19 are rejected on the same grounds.
Eagle teaches the essential amino acids isoleucine, leucine, phenylalanine and valine with their corresponding keto acid analogs in mammalian cell cultures (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. KSR B teaches that it is rational to substitute one known, equivalent element for another to obtain predictable results. In the instant case, Eagle teaches valine can be provided as α-ketoisovlareic acid in a culture medium for mammalian cells. One would have had a reasonable expectation of success since Eagle teaches amino acids can be provided as their keto acid analogs in a minimal essential media. 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 evidenced by Rudman as applied to claim 8 above, and further in view of Eagle et al. and Jones et al. and 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 are reiterated. Fike teaches a derivative of α-ketoisovaleric acid (valine) in a cell culture media.
The art is silent regarding a sodium salt of α-ketoisovalerate (claims 16 and 17).
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 some of the amino acids can be replaced by immediate precursors as the corresponding keto acids (see text below Table 1). The art teaches this substitution relates to the form in which the amino acid may be supplied (see text below Table 1). 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).
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). It is also noted Jones teaches wild type Cho cells can utilize the α-ketoacids corresponding to leucine and isoleucine (page 241, second paragraph).
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 substitute α-ketoisovlareic acid for valine in the culture medium for CHO cells taught by Fike. KSR B teaches that it is rational to substitute one known, equivalent element for another to obtain predictable results. In the instant case Fike cultures mammalian cells and Eagle teaches valine can be provided as α-ketoisovlareic acid in a culture medium for mammalian cells. One would have had a reasonable expectation of success since Eagle teaches amino acids can be provided as their keto acid analogs in a minimal essential media and Jones explicitly teaches CHO cells can successfully be cultured in medium in which valine is replaced with α-ketoisovlareic acid.
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 13 February 2016 are acknowledged.
The arguments are made in light of amended claims 8 and 25. New grounds of rejection have been necessitated by claim amendment.
CONCLUSION
No Claims Are Allowed
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 extension fee 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 date of this final action.
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) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653