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 .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-7) in the reply filed on 10/22/2025 is acknowledged. The traversal was not found persuasive in the action filed 03/03/2026 and was therefore made FINAL.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2021/079085, filed 10/20/2021.
Applicant' s claim for the benefit of a prior-filed parent application EP20203086.2, filed on 10/21/2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is 10/21/2020.
Claims Status
No claims are canceled, no claims are newly added, claims 8-15 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-7 have been considered on the merits. All arguments have been considered.
Withdrawn Objections & Rejections
Applicant's response filed 05/27/2026 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 03/03/2026 are hereby withdrawn.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
Claim Rejections - 35 USC § 112(a) (Maintained)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 4-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 1: The claim recites a poloxamer with a polypropylene oxide block <700g/mol. This is interpreted as a polypropylene oxide block that has a molecular weight from 0-700 g/mol.
Table 1 of the instant specification teaches 23 examples of poloxamers, 10 of which are in the required molecular weight range for the PPO bock, below 700 g/mol. Table 1 teaches poloxamers ranging from 327 g/mol PPO and higher, but there are no examples of species below 327 g/mol.
Thus the species of poloxamer taught by the instant specification are not sufficient to demonstrate that Applicant had possession of the broad genus of poloxamers with a PPO oxide block of 700g/mol or less with an ethylene oxide percentage of >45%.
Wilson et al (WO 2019/125783 A1) teach poloxamers, especially poloxamer 188, are used in cell culture media processes and the addition of poloxamers to cell culture media improves cell viability (p1 [0003])
Wilson teach a poloxamer has the general formula of formula I (p2), shown below, in which x and z vary independently:
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530
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Wilson teach Y is ~15-26 and x+z is 81-100 with an average molecular weight of 6,000 g/mol – 8,000 g/mol (p3 [008]). Wilson further teach a negative relationship between peak molecular weight and poloxamer performance, which predicts lower molecular weight poloxamer 188 will have better performance in cell culture media (Figure 4, p4 [0014]). Wilson further teach one might try to improve poloxamer performance in cell culture by providing a low average molecular weight poloxamer (p4 [0017]).
No examples of poloxamers with a PPO block molecular weight of less than 300 g/mol are found in the art.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.”
While the instant specification and art teach some specific examples of cell culture media comprising poloxamers, and poloxamers are described in the art, there is insufficient guidance for all poloxamers with a PPO block of < 700 g/mol and an EO% of >45%. No poloxamers are disclosed in either the art or the instant specification with a PPO block below 327 g/mol.
The gap between the limited number of structures corresponding poloxamers with a PPO block of < 700g/mol and EO percentage of >45% as described in the instant specification and art compared to the all poloxamer structures with a PPO block of < 700g/mol and EO percentage of >45%. Given this large gap, the specification fails to support the broad genus of “poloxamers with a PPO block of < 700g/mol and EO percentage of >45%” as claimed such that one skilled in the art can reasonably conclude the inventor had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 103 (Maintained)
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.
Claims 1-4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable in view of Moreira et al (J Chem Tech Biotechnol (1995) 62;1-14) in view of Wilson et al (WO 2019/125783 A1), and as evidenced by Zarrintaj et al (Acta Biomaterialia (2020) 110;37-67), Gibco(2026) (DMEM formulation sheet [online] Gibco [retrieved on 02/12/2026]. Retrieved from the Internet: https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/mammalian-cell-culture/dulbecco-modified-eagle-medium-formulation?srsltid=AfmBOoqecDsAS3NgBWp_SwcmJ93R_p22HbwY3lj6IfI4s6VsG4YwHcs-) and Wei et al (Scientific Reports (2016) 6:31175;1-6).
Regarding claims 1-3: Moreira teach methods for large scale culture of animal cells (abstract). Moreira teach cell culture media with and without Pluronic F-68 (also known as poloxamer 188) (p2 col2 ¶6). Moreira teach that the addition of surfactants such as Pluronic F-68 is required to protect cells from bubbles (p2 col2 ¶2).
Moreira do not teach the poloxamer has a PPO block of <700 g/mol.
Wilson teach poloxamers compositions for use as a shear protectant in cell culture (abstract). Wilson further teach the addition of poloxamers, especially Poloxamer 188, to cell culture media improves cell viability significantly (p1 [003]). Wilson teach that poloxamers with lower numbers of PPO (and therefore lower PPO block molecular weight) will have better performance in cell culture (Figure 1).
Wilson teach the structure of poloxamers has the general formula I, shown below:
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505
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Wilson further teach that x and z independently range preferably from 5-150 and y preferably ranges from 15-67 (p2 [0004]).
While Wilson do not explicitly disclose a poloxamer with a PPO block of <700 g/mol, Wilson do disclose low average molecular weight poloxamer provides superior performance and that it is possible to manufacture low average molecular weight poloxamer according to specification (p5 [0027]).
It would have been obvious to one of ordinary skill in the art to adapt the cell culture media comprising a poloxamer of Moreira by using a poloxamer with a PPO block with a low molecular weight as taught by Wilson.
One of ordinary skill in the art would have been motivated to modify the cell culture media comprising a poloxamer as taught by Moreira by using a poloxamer with a PPO block of low molecular weight as taught by Wilson because Wilson teach poloxamers with lower PPO numbers have a reduced decrease in cell culture performance (improved performance).
One would have had a reasonable expectation of success because Moreira teach use of Pluronic F-68 and that use of the Pluronic is required to protect cells from bubbles (p2 col2 ¶2).
Regarding claim 4: The teachings of Moreira are discussed supra. Moreira also teach studies are performed with and without 0.2% w/v Pluronic F-68 in cell culture medium (p3 col1).
One of ordinary skill in the art would understand 0.2% w/v is equivalent to 2 g/L and thus reads on “the poloxamer in an amount between 0.1 to 10g/L”.
MPEP 2131.03 reads “"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated' if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985)”
Regarding claim 7: The teachings of Moreira are discussed supra. Moreira further teach the cell culture medium is Dulbecco’s modified Eagle’s medium (DMEM) supplemented with fetal calf serum (p3 ¶2). As discussed below, DMEM and fetal calf serum (also known as FBS) comprise the components required by the instant claim.
As evidenced by the Gibco(2026) DMEM formulation sheet, DMEM contains one or more of the following: a saccharide (glucose), amino acids (L-arginine), vitamins (folic acid), salts (sodium chloride), buffer components (sodium phosphate monobasic) and co-factor (thiamine).
As evidenced by Wei, fetal calf serum is a source of nucleic acid components such as mRNAs (abstract).
Thus the teachings of Moreira and Wilson render obvious the invention as claimed.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Moreira et al (J Chem Tech Biotechnol (1995) 62;1-14) in view of and Wilson et al (WO 2019/125783 A1), as applied above to claims 1-4 and 7, and further in view of Rayner-Brandes et al (WO 2015/003773 A1).
Regarding claims 5-6: The teachings of Moreira are discussed supra. Moreira do not teach the cell culture medium is a chemically defined medium or that the medium is a dry powder.
Rayner-Brandes teach cell culture media comprising polymer components (abstract). Rayner-Brandes teach that the cell culture medium is a chemically defined cell culture medium that is dry powder (claims 1 and 7 of Rayner-Brandes).
It would have been obvious to one of ordinary skill in the art to adapt the cell culture medium of Moreira by using a chemically defined culture medium or a medium that is dry powder as taught by Rayner-Brandes.
One of ordinary skill in the art would have been motivated to modify the culture medium as taught by Moreira with the teachings of Rayner-Brandes because Rayner-Brandes teach poorly chemically defined media is poorly characterized and difficult to manufacture with consistent quality (p2 ln24-30). Rayner-Brandes also teach one would be motivated to use dry powder medium because liquid cell culture media has reduced shelf life and has difficulties for shipping and storage (p3 ln 1-5).
One would have had a reasonable expectation of success because Rayner-Brandes disclose many cell culture media are offered as finely milled dry powder mixtures, and chemically defined media is easier to manufacture with consistent quality, and thus the results would have been predictable.
Thus the teachings of Moreira, Wilson and Moreira and Rayner-Brandes render obvious the invention as claimed.
Response to Arguments
The responses are directed to the Arguments filed 05/27/2026. All arguments have been considered.
Regarding Arguments directed to 35 USC § 112(a):
Applicant argues that the specification contemplates poloxamers with y = 5 to 12 PPO repeat units and thus the invention satisfies the written description requirement for poloxamers with a molecular weight of less than 300 g/mol.
As stated in the rejection above, one species is disclosed to exemplify to broad genus of a poloxamer with a polypropylene oxide block <700 g/mol and an ethylene oxide percentage of >45%. A single species is not considered sufficient to support that the Inventors had possession for the entire scope of the genus.
The claimed range of <700 g/mol of PPO block encompasses PPO blocks less than 300 g/mol. For example, a PPO block of 100 g/mol means fewer than 2 PPO units considering MW of propylene oxide being 58.08 g/mol. Technically some of the claimed ranges appear not to be synthesized as a poloxamer. Yet, the specification showed only a single example having 327 g/mol of PPO for the claimed range of <700 g/mol.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
The argument is unpersuasive and the rejection is maintained.
Regarding Arguments directed to 35 USC § 103:
Applicant argues that Moreira does not teach methods for large scale culture of animal cells and that the purpose of Moreira is different than that of the instant application. It is noted that the elected invention is drawn to a composition, a cell culture medium and not a method.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., methods for large scale culture of animal cells; coculture with animal cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The claim are silent as to a scale of a culture and a type of cell and arguments against limitations that are not in the claims are not persuasive.
Furthermore, Moreira is drawn to cell culture in 3 dm3 (3 liter) volume bioreactors for culture of animal cells (p3 col1 ¶1) which is considered to read on large scale culture of animal cells, if such were required by the claims.
Applicant argue Moreira do not provide motivation to use the poloxamers of Wilson or to modify Wilson.
MPEP 2144.09 reads “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990)”.
Wilson and Moreira are drawn to poloxamer of similar chemical structure with similar properties and thus it would be obvious to substitute the poloxamers one for the other.
The arguments are unpersuasive and the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 ANDREA LYNNE MORRIS SPENCER whose telephone number is (571)272-3328. The examiner can normally be reached Monday-Friday 9:00-5:00.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631
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