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 20 April 2026. Claim 5 was not rejected in the previous Office Action. A second Non-Final Office Action is set forth below.
CLAIMS UNDER EXAMINATION
Claims 1-13 are pending and have been examined on their merits,
PRIORITY
Provisional Application 63/010,536, filed on 15 April 2020, is acknowledged.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
Claim Objections
Claim 2 is objected to because of the following informalities: The claim recites “the method according to claim 1 the medium is supplemented”. The claim should recite “the method according to claim 1, wherein…”. Appropriate correction is required.
REJECTIONS
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 1-13 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 1 recites conditions suitable for inoculation of the medium with “a eukaryotic cell” (singular). The claim also recites the medium is held “in the absence of cells” (plural). It is unclear if claim 1 is directed to conditions for a single cell (a eukaryotic cell), or a plurality of cells (“…cells”). The metes and bounds of the claim are unclear. Appropriate correction is required. All dependent claims are included in this rejection.
Claim 7 recites “a bioreactor”. It is unclear if the claim 7 is referring to the vessel recited in claim 1, or if the claim means the method requires a vessel and a bioreactor. Appropriate correction is required.
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 9 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.
Claim 9 recites “at least about 10 hours”. Neither the claims or specification define the term “about”. Therefore “about 10 hours” is interpreted to include values below 10 hours. The claim is not further limiting because the base claim recites “at least 10 hours”.
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 1-7 and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable Nishiuch et al. (cited in IDS; Cytotoxicity Of Cysteine In Culture Media. In Vitro. Volume 12(9) 1976: 635-638) in view of Chaderjian et al. (Effect of Copper Sulfate on Performance of a Serum-Free CHO Cell Culture Process and the Level of Free Thiol in the Recombinant Antibody Expressed. Biotechnol Progress, 21: 550-553).
Nishiuch et al. teach commercially available culture medias which contain cysteine in place of, or in addition to, cystine (page 635, first paragraph of Introduction). The art teaches 1mM cysteine is highly toxic to cultured mammalian (eukaryotic) cells (Abstract; page 636, left column, last paragraph). This toxicity was eliminated completely by preincubation of the media at 37°C for 24 hours before use (Abstract; page 637, left column first paragraph). Media containing cysteine was incubated at 37°C without cells (page 637, left column, third paragraph). Said temperature is interpreted to be a condition suitable for inoculation. The art teaches media is in a tube (vessel) (page 636, left column, second paragraph).
The art does not teach supplementing the medium with a redox trace metal after the medium is added to the vessel.
Chaderjian teaches a method of growing a CHO cell (a mammalian, eukaryotic cell; Abstract). Chaderjian teaches bioreactors comprising DMEM/F12 media (page 551, left column, third paragraph). Chaderjian prepares a CuSO4 solution (page 551, left column, first paragraph; page 551; left column, third paragraph). To test different starting concentrations of CuSO4, 0, 5, 50 or 100 µm CuSO4 is added to each bioreactor (page 551, left column, first paragraph; page 551; left column, third paragraph). The art teaches doing so adds Cu2+ ions (hence, copper, a redox reactive trace metal) (page 551, left column, first paragraph). Therefore the art teaches media in a vessel can be supplemented with a redox reactive trace metal.
Chaderjian also teaches the following:
The art teaches copper is an essential metal for animal cell cultures (page 550, right column, second paragraph). In mammalian cells, trace amounts of copper are required for the function of many metalloproteins (same cited section). The art teaches acceptable viability is obtained with added copper sulfate (see last sentence of page 551 bridging first two lines on page 552). No detrimental effect on cell growth, metabolism in productivity is observed (page 553, left column, Summary section).
It would have been obvious to combine the teachings of the prior art by adding copper to the cysteine containing medium taught by Nishiuch. One would have been motivated to do so since Chaderjian teaches copper is essential for mammalian cell culture. The skilled artisan would add copper since it is required for the function of cell metalloproteins. The skilled artisan would use a medium with cysteine and copper since both are used to culture eukaryotic cells. It is prima facia obvious to combine two compositions (cysteine and copper) when each is taught by the prior art to be used for the very same purpose: eukaryotic culture. See In re Kerkoven. Therefore, then, barring unexpected results, one would reasonably expect enhanced, additive, or synergistic activity to be observed by combining the compositions. One would have had a reasonable expectation of success adding copper to a medium already in a vessel since Chaderjian teaches copper can be added to culture medium which is already present in a vessel. MPEP teaches selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results (See 2144.04). One would have expected similar results since each reference is directed to a method of preparing a medium for eukaryotic culture. Therefore claim 1 is rendered obvious.
Nishiuch teaches MEM-10BS media is supplemented with SH compounds by adding concentrated solutions of the compounds to the media immediately before use (see page 636, left column, second paragraph). The media is incubated without cells for 24 hours before use (page 637, left column, first sentence). Therefore the art is interpreted to teach the medium is supplemented with cysteine before addition of the medium to the vessel. Therefore claim 2 and 4 are rendered obvious.
Nishiuch teaches 1mM cysteine in a culture media held for 24 hours before inoculation (supra). Therefore claim 3 is included in this rejection.
Nishiuch teaches MEM-10BS media is supplemented with SH compounds by adding concentrated solutions of the compounds to the media immediately before use in culture (supra). While the art does not explicitly teach supplementing cysteine after addition of the medium to the vessel, the MPEP teaches selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results (See 2144.04). Therefore claim 5 is rendered obvious.
The specification states a “bioreactor” is an in vitro culture system that has been designed to initiate, maintain and direct cell growth in a well-defined and tightly controlled culture environment ([0145]). The vessel taught by Nishiuch is interpreted to read on a bioreactor. Even arguendo it did not, Chaderjian teaches a bioreactor (see page 551, let column, third paragraph). Claim 6 is included in this rejection.
Nishiuch teaches preincubating media prior to inoculation. This reads on claim 7.
Nishiuch teaches 1mM cysteine in a culture media held for 24 hours (supra). Therefore claim 9 is included in this rejection.
Chaderjian prepares copper sulfate solution (page 551, left column, third paragraph). The art teaches doing so adds Cu2+ ions (hence, copper) (page 551, left column, first paragraph). Therefore claim 10 is included in this rejection.
Chaderjian teaches addition of a CuSO4 solution (page 551, left column, third paragraph). The solution contains 5, 50 or 100 µm (same section). The specification does not define the term “about”. Therefore the concentration taught by the art is interpreted to read on the claim limitation. Therefore claim 11 is included in this rejection.
Chaderjian teaches the following culture conditions: dissolved oxygen of 60±5%, pH at 7.1 ± 0.1 and 37°C (see page 551, left column, third paragraph). Claim 12 is included in this rejection.
Nishiuch cultures mammalian cells (supra). Therefore claim 13 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Nishiuch in view of Chaderjian as applied to claim 1 above, and further in view of Ritacco et al. (previously cited; Cell culture Media for Recombinant Protein Expression in Chinese Hamster Ovary (CHO) Cells: History, Key Components, and Optimization Strategies. Biotechnol Prog., 2018, Vol. 34 (6) pages 1407-1426).
Claim 1 is rejected on the grounds set forth above. The teachings of Nishiuch and Chaderjian are reiterated.
Nishiuch teaches a medium comprising cysteine for culturing eukaryotic mammalian cells. The art is silent regarding the use of a cysteine derivative.
Ritacco teaches most cell culture media contain non-essential amino acids, including cysteine (page 1411, right column, 6th paragraph). Ritacco teaches S-sulfocysteine is a replacement cysteine source and antioxidant in cell culture media (page 1412, right column, fourth paragraph).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to substitute a S-sulfocysteine for cysteine in the disclosed method. as KSR B teaches that it is rational to substitute one known, equivalent element for another to obtain predictable results. In the instant case, Ritacco teaches S-sulfocysteine can be used as a replacement cysteine source. One would have been motivated to do so since the art teaches it acts as an antioxidant in cell culture media. Therefore claim 8 is 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 20 April 2026 are acknowledged. New grounds of rejection are set forth above.
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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