DETAILED ACTION
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 .
This action is in response to the papers filed on 06/20/2023. Claims 1-21 are currently pending as per claims filed on 06/20/2023 and are subject to examination to which the following grounds of rejection are applicable. Claims 1 and 8 are independent claims.
Priority
The instant application a This application is a 371 of PCT/EP2021/087010 filed 12/21/2021, which claims foreign priority to LUXEMBOURG 102338 filed 12/21/2020.
Thus, the earliest possible priority for the instant application is 12/21/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/20/2023, 08/07/2025, 11/13/2025 were filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: “Claim 1 recites “A process for the in vitro storing and/or transporting of cells, comprising the following steps:
STEP 1 : contacting the cells with an aqueous thermo-reversible gelling composition C, said composition C being in a liquid form and comprising, in an aqueous medium: (B) a thermo-reversible gelling polysaccharide selected from carrageenan, gellan gum and konjac gum; and (B) carboxymethyl cellulose as a thickening agent”
However, it appears that the applicants’ intentions was to use (A) wherein the first recitation of “(B)” occurs in line 5. Appropriate correction is required.
Further, it is recommended to amend claim 1, line 5 to recite “…selected from the group consisting of carrageenan, gellan gum and konjac gum…”
It is recommended to amend claim 8, line 3 to recite “…selected from the group consisting of carrageenan, gellan gum and konjac gum….”
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 1-21 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 applicant regards as the invention.
Claim 1 is rejected in line 4 because of the recitation “in an aqueous medium”. Step 1 of claim 1 requires that the composition C is in liquid form. The phrase appears to be redundant. Thus, it is unclear whether the phrase refers to a liquid culture comprising (A) and (B) or has any other meaning. As such the metes and bounds are indefinite.
Claim 1 recites the term “and/or” in lines 1 and 9. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only in vitro storing, or all of in vitro storing and transporting of cells, or, “or” would imply that the two processes are in the alternative. Appropriate correction is required.
Claim 1 recites at line 8 the phrase “by decreasing the temperature". The recitation of term “decreasing the temperature” is a relative term and renders the claim indefinite. This term “temperature’ is not defined by the claim, the specification does not provide suitable support for that would allow one to ascertain the intended meaning, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention with respect to this recitation. Decreasing the temperature from what starting point? Decreasing the temperature of what exactly? The recitations is unclear, as such the metes and bounds of the claim are indefinite.
Claims 2-21 ultimately dependent upon and inherit the deficiencies of claim 1.
Claim 2 recites at line 3 the phrase “by increasing the temperature". The recitation of term “increasing the temperature” is a relative term and renders the claim indefinite. This term “temperature’ is not defined by the claim, the specification does not provide suitable support for that would allow one to ascertain the intended meaning, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention with respect to this recitation. Increasing the temperature from what starting point? Increasing the temperature of what exactly? The recitations is unclear, as such the metes and bounds of the claim are indefinite.
Claims 6-7 and 17-18 ultimately dependent upon and inherit the deficiencies of claim 2.
Claim 3 is indefinite in its recitation of “the aqueous medium of composition C”. There is not proper antecedent bases for “the aqueous medium of composition C” in the claim. Claim 1 recites ““the aqueous medium of composition C”. Appropriate correction is required.
Claims 9, 10, 11, 12 , 19 and 20 recite “the compound” or “compounds”. There is not proper antecedent bases for the compound or compounds in these claims or parent claim 8.
Claim 16 recites, “The process of claim 5, wherein STEP 2 is carried out by lowering the temperature between 1 and 15°C.” It is unclear whether the applicants’ intended meaning is that the previous temperature is lowered BY 1 and 15°C or if applicant intends the final temperature TO BE between 1 and 15°C.” This is not defined by the claim, the specification does not provide suitable support for that would allow one to ascertain the intended meaning, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention with respect to this recitation. The recitations is unclear, as such the metes and bounds of the claim are indefinite.
Claim 21 which depends on claim 13 is indefinite in its recitation of “further comprises ethylenediaminetetraacetic acid (EDTA)”. Claim 13 already comprises EDTA. Thus, it is unclear if the recitation of “further comprises ethylenediaminetetraacetic acid (EDTA)” in claim 21 is an additional addition of EDTA or the claim is attempting to define the concentration of EDTA in the aqueous medium. As such the metes and bounds of the claim are indefinite.
Claim Rejections - 35 USC § 103
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 8-12, 14-17 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Fabre et al. (US 8,900,842 B2; hereafter “Fabre”) in view of Popa et al. (US 2004/0127841 Al; hereafter “Popa”) and Hernández et al. ( Hernández MJ et al., Food Science and Technology International. 2001, IDS filled 11/13/2025; hereafter “Hernández”)
The independent claims 1 and 8 are provided below for ease of reference:
Claim 1 recites “A process for the in vitro storing and/or transporting of cells, comprising the following steps:
STEP 1 : contacting the cells with an aqueous thermo-reversible gelling composition C, said composition C being in a liquid form and comprising, in an aqueous medium: (B) a thermo-reversible gelling polysaccharide selected from carrageenan, gellan gum and konjac gum; and (B) carboxymethyl cellulose as a thickening agent
STEP 2: thermo-gelling the composition C in contact with the cells as obtained in step 1, by decreasing the temperature, whereby a hydrogel is obtained, embedding the cells; and STEP 3. storing and/or transporting the cells embedded in the hydrogel as obtained in step 2.”
Claim 8 recites “A composition C suitable for the process of claim l comprising, in an aqueous medium: (A) a thermo-reversible gelling polysaccharide selected from carrageenan, gellan gum, and konjac gum; and (B) carboxymethyl cellulose as a thickening agent” Regarding claims 1, 8 and 9 , Fabre teaches “…a method of storing and/or transporting in vitro two-dimensional cell cultures…” (Abstract). Fabre teaches the cell culture is coated with a gelatine solution (Column 4, Line 22), made with a type A pigskin gelatine (Column 5, Line 25-26). Fabre teaches the gel is liquified at one temperature prior to cell contact and then the gel is allowed to solidify at a lower temperature (Column 4, Lines 52-60). Gels containing cells can be stored for up to four days (Column 8, Lines 59-61). Fabre teaches “When one wants to use the immobilized culture, the plate is incubated with solid gelatine within a cell incubator until the complete liquefication of the gelatine, preferably at 37° C.” (Column 4, Line 64-66). This read on the thermo-reversibility of the gel as recited in claim 1.
Fabre does not specifically teach the gel is composed of carrageenan, gellan gum or konjac gum and carboxymethyl cellulose.
Popa cures the deficiencies of Fabre as Popa teaches the development and characterization of a hydrogel systems based on natural origin polymers, namely, alginate and carrageenan (Abstract). Popa teaches “Thermo-reversible gels, such as carrageenan (which reads on the recitation of carrageenan in instant claims 1, 8 and 9), melt at elevated temperature and the gelation of the biopolymer is obtained by lowering the temperature. The temperature-induced gelation allows for an easy formation of gels with different shapes, emphasizing the versatility of the carrageenan.” (Pg. 3952, 2nd Column). Popa showed successful encapsulation and growth of cells (Figs. 4-6) and concluded “In fact, all the results obtain demonstrated that alginate/κ-carrageenan can be an innovative and adequate alternative for the development of carrier systems to encapsulate cells or other bioactive agents of relevance in tissue engineering applications.” (Conclusions).
Fabre and Popa do not teach that sodium carboxymethyl cellulose is used as a thickening agent to alter the characteristics of a carrageenan-based hydrogel.
Hernández teaches sodium carboxymethylcellulose with carrageenan as a known hydrocolloid mixture effecting rheology/viscosity and specifically discusses the use of sodium carboxymethylcellulose as a thickening agent (Pg. 384, 2nd Column, 2nd Paragraph). Hernández teaches two separate carrageenan, including kappa-carrageenan (Pg. 384, 1st column, 2nd Paragraph) as recited in instant claim 19.
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the instant application to have modify the teachings of Fabre who demonstrates a method (and composition) for storing and/or transporting cells using a thermo-reversible gel comprising gel components to substitute the gel components of their invention with the hydrogel systems based on carrageenan as taught by Popa to be an innovative and adequate alternative to other cell encapsulation components.
Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Moreover, it would have been prima facie obvious to a person of ordinary skill in the art at the time of the instant application to further include sodium carboxymethylcellulose in a gel formulation with carrageenan as taught by Hernández. One would have been motivated to use the known rheology/thickening components in a carrageenan-based gel system to optimize the hydrogel formulation with the expectation of obtaining a suitable gel formation with the desired mechanical/support properties for the specific embedded cells.
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the same field to give predictable results.
Regarding Claim 2 and 6-7, the combined teachings of Fabre, Popa and Hernandez render obvious the method of claim 1. Moreover, Fabre teaches liquefication of the gelatine containing the cell cultures at 37° C for 3-4 hours. (Column 4, Lines 64-67 transitioning to Column 5, Lines 1-5). 37° C for 3-4 hours reads on the temperature range recited in claim 6.
Regarding Claim 3, the combined teachings of Fabre, Popa and Hernandez render obvious the method of claim 1. Moreover, Fabre teaches their method is suitable for storage and/or transport (Title; Abstract)
Regarding Claim 4, 15 and 17, the combined teachings of Fabre, Popa and Hernandez render obvious the method of claim 1. Moreover, Fabre teaches “To apply the gelatine to the culture, it is firstly necessary to completely liquefy the gelatine solution and equilibrate it to the culture medium temperature, generally at 37° C.” (Column 4, Lines 52-54). These teachings read on the range of temperature recited in instant claims 4, 15, and 17 (30°C -60°C, 30°C -40°C, and 34°C -39°C, respectively).
Regarding Claim 5, the combined teachings of Fabre, Popa and Hernandez render obvious the method of claim 1. Moreover, Fabre teaches the gel is left to solidify at a temperature of 20-25° C (Column 4, Lines 57-61).
Regarding Claim 7 and 18, the combined teachings of Fabre, Popa and Hernandez render obvious the method of claims 1 and 2. Fabre teaches a 2-3 hour gelatine step in which the cells are encapsulated and allowed to solidify and a 3-4 hours gelatine elimination step in which the gel is removed from the cells and they are ready for experimental use (Column 4, Lines 64-67 transitioning to Column 5, Lines 1-5). However, Fabre, Popa and Hernandez do not teach a specific timeframe of less than 3 hours for the gelatine step (Step 2 of instant claim 1) and the gelatine elimination step (Step 4 of instant claim 2) as recited in instant claim 7 OR that these steps in combination would be less than 3 hours as recited in claim 18.
A person of ordinary skill in the art would have been motivated to determine an optimal experimental conditions, such as duration of gelatine step and gelatine elimination step, through routine optimization to maximize the survival and health of the cells obtained from a storage and transport hydrogel prior to further experimental use.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Regarding Claims 10-12 and 20, the combined teachings of Fabre, Popa and Hernandez render obvious the formulation of claim 8. However, Fabre, Popa, and Hernandez together do not teach the specific viscosity of carboxymethyl cellulose to be lower than 40 mPa*s at 25°C at 2% by weight in water as recited in claim 10, or the ratio of the total mass of A/B to be between 15: 85 and 45:60 as recited in claim 11, concentration of compound A+B/Compound C is between 6-10g/L as recited in claim 12 or 8 to 10 g/L as recited in claim 20.
A person having ordinary skill in the art at the time of the instant application would understand that adding carboxymethyl cellulose to a carrageenan-containing hydrocolloid system would modify viscosity rheology as Hernandez teaches that carboxymethyl cellulose could alter characteristics of formulations, such as binding, thickening, stabilization and increased water retention and enhanced formulations with carrageenan as a stabilizer (Hernandez, Pg. 384, 2nd Column, 1st full paragraph). Hernandez also teaches determination of viscosity as a measurement of (Pa*S) via mathematical equations and expressly states “It should be that the aim is not to establish the corresponding rheological models but to define a series of empirical mathematical equations capable of reliably reproducing the apparent viscosity values under the experimental conditions in which they have been measured (Pg. 385, 2nd column, final paragraph transitioning to Pg. 386 1st Column).
Popa teaches evaluation of multiple concentrations of components within their hydrogel formulation and show the concentration effect polymer concentration, ratio, and processing variables (such as hardening time) (Table 1.) and that higher concentrations can be difficult to work with as they produce especially high viscosities (Pg. 3955, 2nd Column, 1st Paragraph).
Therefore, a person of ordinary skill in the art would have been motivated to determine an optimal experimental conditions, such as appropriate concentration (or other result effective variables such as viscosity with respect to carboxymethyl cellulose) of hydrogel components to provide a hydrogel with specific characteristics, through routine optimization to maximize the survival and health of the cells obtained from a storage and transport hydrogel prior to further experimental use.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Regarding Claim 14, the combined teachings of Fabre, Popa and Hernandez render obvious the formulation of claim 8. The formulation components from the combined teachings are not animal derived products and thus the formulation taught by combining the teachings of Fabre, Popa and Hernandez is inherently animal-free.
Regarding Claim 16, the combined teachings of Fabre, Popa and Hernandez render obvious the process of claims 1 and 5. Moreover, Fabre teaches solidifying the gel after contact with cells can occur at temperature as low as 15° C (Column 3, Line 5).
Claims 13 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Fabre et al. (US 8,900,842 B2; hereafter “Fabre”) in view of Popa et al. (US 2004/0127841 Al; hereafter “Popa”) and Hernández et al. ( Hernández MJ et al., Food Science and Technology International. 2001, IDS filled 11/13/2025; hereafter “Hernández”) as applied to claim 8 above and in further view of Melero et al. (Advances in Materials Science and Engineering, 2019; hereafter “Melero”)
Regarding claim 8, Fabre, Popa, and Hernández together teach the composition of claim 8, as iterated above in the 103 rejection, the content of which is incorporated herein, in its entirety.
Regarding Claims 13 and 21, Fabre, Popa, and Hernández together do not teach the addition of EDTA or that the content of EDTA is less than 1mM.
Melero teaches Ethylenediaminetetraacetic acid (EDTA) was well known in the art as a chelator and as a component of hydrogels and that chelation restricts reactivity of different cations, such as Ca2+ (Introduction, Paragraphs 9-10 and 12).
It would have been prima facie obvious to a person of ordinary skill in the art at the time of the instant application to have modified the hydrogel formulation from the combined the teachings of Fabre, Popa, and Hernández to include EDTA as a chelating agent. One would have been motivated to include EDTA to enhance the gel formulation as it would restrict reactivity of cations reducing effects (such as uncontrolled ionic crosslinking by free cations).
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the prior to give predictable results.
Further, a person of ordinary skill in the art would also be aware of the effect of EDTA in hydrogel formulations and would have been motivated to determine an optimal concentration through routine optimization to achieve a desired hydrogel for cell culture.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Conclusion
Claims 1-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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