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 01 October 2025.
CLAIMS UNDER EXAMINATION
Claims 1-7, 9-17 and new claims 21-23 have been examined on their merits.
PRIORITY
Provisional Application 62/840,617, filed on 30 April 2019, is acknowledged.
WITHDRAWN REJECTIONS
The rejection of claims 1-7 and 9-17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn due to claim amendment.
REJECTIONS
The previous rejections have been modified to address new claims 21-23.
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, 9, 11-17 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over She et al. (previously cited; Compositions and methods for cell cryopreservation. US20180092348) in view of Hubel et al. (previously cited; Cryopreservative compositions and methods. US20170172138) and Austen et al. (previously cited; Methods and Compositions for Improving the Viability of Cryopreserved Cells. US2012/0128641 2012).
She et al. teach a composition for cell cryopreservation (Abstract). The composition has low toxicity to cells and tissues, and promotes survival and retention of viability of the biological material during cryopreservation (Abstract).
The composition comprises a permeating protectant, a saccharide and a macromolecule ([0008]).
The permeating protectant may be glycerol (a sugar alcohol) ([0021]). The composition can comprise one or more permeating cryoprotectants at a concentration ranging from about 0.5% (w/v) to about 80% (w/v) ([0039]). The art teaches the volume of the composition can be 10, 50, 100, 500 or 1 L ([0067]). The molecular weight of glycerol is known in the art as 92.09382 g/mol.
The saccharide can include sucrose, glucose and fructose ([0022]; hence sugars). The sugar may be about 0.05M (50 mM, less than 300 mM) [0040]).
In certain embodiments, the macromolecule comprises albumin ([0038]). She teaches the composition can include about 1% (w/v) to about 10% (w/v) of the macromolecule ([0008]). This reads on the claimed concentration of albumin, which is optional.
She teaches that while DMSO is frequently used it is physiologically toxic and known to cause high blood pressure, nausea and vomiting when the cells are transfused to a recipient. Further, the toxicity of DMSO tends to debilitate the cells' survival rates and/or functions after the thawed cells are cultured or transfused into a recipient's body ([0005]). The composition is substantially free or free of DMSO ([0029]). DMSO can be less than 4% ([0106]).
The composition can comprise “polymers” ([0100]). The art identifies polymers as non-permeating cryoprotectants ([0084]).
While She teaches a sugar component and a sugar alcohol component, She does not teach the molar ratio range recited in claim 1.
While She teaches the composition can include a polymer, the art does not teach a poloxamer at a concentration between 3-8%.
Hubel teaches a cryopreservative composition (Abstract). The cryopreservative composition includes a sugar component and a sugar alcohol component, and is effective for storing and recovering cells without requiring dimethyl sulfoxide (DMSO) (Abstract).
The sugar component can include trehalose, fructose, sucrose, glucose, or a combination of sugars ([0004]). Hubel teaches a sugar component of 0.1 mM to 300 mM ([0097]). Hubel uses trehalose (a sugar) in concentrations of 300 mM ([0014] and 150 mM ([0042]).
The sugar alcohol component can include sorbitol, ethylene glycol, inositol, xylitol, mannitol, or a combination of sugar alcohols ([0005]). Hubel teaches the sugar alcohol component is provided at a concentration of 0.1 M to 1.4 M (hence 100 mM to 1.4 M) [0099]). Examiner notes the amounts taught by the prior art would encompass a 1:1 ratio of sugar to sugar alcohol (for example 300 mM sugar to 300 mM sugar alcohol). The amounts taught by the prior art would also encompass a 1:50 ratio (for example 2 mM sugar and 100 mM sugar alcohol is a 1:50 ratio)
Austen teaches polymers for increasing the viability of cryopreserved cells (Abstract). The polymer can be added during freezing ([0006]). The polymer stabilizes the cell membrane ([0006]). The polymer can be added with a cyroprotectant, e.g. before the cells are frozen ([0039]). The cells can be frozen in the presence of one or more cryopreservative agents ([0047]). Trehalose, glucose, lactose and maltose (hence, sugars) and glycerol (hence, a sugar alcohol) are identified as cryopreservation agents by Austen ([0047]).
Austen teaches as would be appreciated by one of skill in the art, the concentration of polymer needs to sufficiently stabilize the membranes of the cryopreserved cells and improve viability may vary depending on the polymer used, the cells, the concentration of the cells and downstream application [0048]. The concentration ranges from approximately 1-20 mg of polymer per ml of cryopreserved cells ([0048]).
Austen teaches the use of the polymer, poloxymer P188 (Abstract); [0033]). Austen teaches Poloxymers are also known as poloxamers ([0005]).
It would have been obvious to use a sugar component and a sugar alcohol component in the claimed range of ratios. One would have been motivated to do so since She teaches a cryopreservative comprising a sugar and a sugar alcohol and Hubel teaches sugar and sugar alcohol can be used in a cryopreservative in amounts that include 1:50 to 1:1 ratios. One would have had a reasonable expectation of success since Hubel teaches the components can be included in a cryopreservative in amounts that read on the claimed range. One would have expected similar results since both references are directed to compositions used to cryopreserve cells.
It would have been obvious to use a poloxamer in the composition taught by She. One would have been motivated to do so since She teaches a polymer and Austen teaches poloxamer can be used as a polymer in a medium for cryopreservation. One would have had a reasonable expectation of success using a polymer since Austen teaches polymers can be used with sugars and sugar alcohols during freezing. One would have expected similar results since both references are directed to compositions for cell cryopreservation.
It would have been obvious to use poloxamer in the claimed amount. One would have been motivated to do so since She teaches a polymer as a non-permeating cryoprotectant and Austen teaches polymers can be added to stabilize the cell membrane during freezing. Austen teaches the concentration ranges from approximately 1-20 mg of polymer per ml of cryopreserved cells. Austen teaches the concentration of polymer used needs to sufficiently stabilize the membranes of the cryopreserved cells and improve viability may vary depending on the polymer used, the cells, the concentration of the cells and downstream application. The skilled artisan would optimize the amount of polymer based on the amount of cells being preserved. One would have had a reasonable expectation of success using a polymer since Austen teaches polymers can be used with sugars and sugar alcohols during freezing. One would have expected similar results since both references are directed to compositions for cell cryopreservation. Therefore claim 1 is rendered obvious.
She teaches sugars can be used at 0.05M (50 mM) [0040]). Therefore claim 2 is included in this rejection.
She teaches sugar can include sucrose, glucose and fructose. Therefore claim 3 is included in this rejection.
She teaches the sugar can be trehalose ([0022]). The sugar may be about 0.05M (50 mM) [0040]). Therefore claim 4 is included in this rejection.
Hubel teaches the sugar alcohol can be 0.1 M to 0.6 M of the composition ([0099]). MPEP 2133.03 discloses “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).Therefore, ta range of 0.3M to 0.8M is prima facie obvious. Claim 5 is included in this rejection.
She teaches the permeating protectant may be glycerol (a sugar alcohol) ([0021]). Therefore claim 6 is included in this rejection.
Hubel teaches the sugar alcohol can be 0.1 M to 0.6 M of the composition ([0099]). MPEP 2133.03 discloses “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).Therefore, the range of 0.3M to 0.8M is prima facie obvious. Claim 7 is included in this rejection.
She teaches albumin as a macromolecule (supra). The composition can include about 1% (w/v) to about 10% (w/v) of a macromolecule ([0008]). Therefore claim 9 is included in this rejection.
She teaches the composition may comprise one or more amino acids ([0101]). In certain embodiments, the amino acid concentration in the present composition is 0.01-10.0% by weight, or 0.1-1.0% by weight ([0104]). One would optimize the amount based on the desired level of amino acids to be provided to the cryoprotectant. Therefore claim 11 is included in this rejection.
She teaches the amino acid can be isoleucine ([0102]). Therefore claim 12 is included in this rejection.
She teaches the composition can include one or more amino acids (supra). Therefore claim 13 is included in this rejection.
She teaches the amino acid can be alanine ([0102]). Therefore alanine as a second amino acid is rendered obvious in claim 14.
She teaches the cells can be present in the cryopreservation composition ([0113]). Therefore claim 15 is included in this rejection.
She teaches the cell can be sperm (hence, a gamete) ([0117]). Therefore claim 16 is included in this rejection.
Because She teaches the cell is in a composition for cell cryopreservation that promotes survival (supra), it is interpreted to read on claim 17.
Austen teaches poloxymer P188 is used to increase the viability of cells ([0006] [0033] [0039]). Therefore claim 21 is rejected.
She teaches the composition may or may not comprise one or more amino acids ([0101]). The amino acids include glycine, alanine, asparagine, aspartic acid, glutamic acid, proline and serine ([0102]). Therefore claim 22 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over She in view Hubel and Austen as recited in the rejection of claim 1 above, and further in view of Agulnick et al. (previously cited; Cryopreservation of encapsulated pancreatic endoderm cells. US Patent 10695380; prior publication 20180064763).
Claim 1 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. She teaches the composition can comprises salts ([0108]). The art is silent regarding the amount of salt.
Agulnick teaches a composition for cryopreservation (column 46, lines 61-63). The composition may include glucose and NaCl at about 0.5-0.9% (column 48, lines50-55).
It would have been obvious to combine the teachings of the prior art by using a salt in the composition taught by She. One would have been motivated to do so since She teaches a cryopreservation composition and Agulnick teaches using a salt t a concentration of 0.5-0.9% in a cryopreservation composition. One would have had a reasonable expectation of success since Agulnick teaches salt can be used a cryopreservative. One would have expected similar results since both references are directed to compositions used to cryopreserve cells. Therefore claim 10 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over She in view Hubel and Austen as recited in the rejection of claim 1 above, and further in view of Nahar et al. (A Comparison of the Preservation of Mouse Adipose Tissue-Derived Mesenchymal Stem Cells Using the University of Wisconsin Solution and Hank's Balanced Salt Solution. Stem Cells Int. 2018 Sep 6;2018:1625464).
Claim 1 is rejected on the grounds stated above. The teachings of the prior art are reiterated. She teaches a cryopreservation composition comprising glucose.
She teaches the components are dissolved in a balanced electrolyte solution (e.g., a saline solution) ([0061]). In one embodiment, the saline solution comprises one or more of the following: Calcium Chloride, Magnesium Sulfate, Potassium Chloride, Potassium Phosphate, Sodium Chloride, Sodium Bicarbonate ([0061]). She also teaches magnesium chloride salt ([0108]).
She does not teach a component comprising all of the ionic component ingredients recited in claim 23.
Nahar teaches Hank's balanced salt solution (HBSS) is one of the main ADSC preservation solutions used clinically (Abstract). The essential function of HBSS is to maintain the pH and osmotic balance as well as provide the cells with water and inorganic ions. HBSS also contains glucose, which provides the cells with energy (third paragraph of Introduction). As evidenced by the arguments made by the Applicant on 01 October 2025, HBSS contains each of the components recited in claim 23. Nahar teaches HBSS possess sufficient function as a preservative solution (See Conclusions section).
It would have been obvious to use HBSS in the composition taught by She. She teaches a composition for cryopreservation and Nahar teaches HBSS is one of the main preservation solutions used clinically. One would have been motivated to use HBSS to maintain the pH and osmotic balance as well as provide the cells with water and inorganic ions. The skilled artisan would use it when preserving ADSC cells.
The skilled artisan would want to combine glucose with an ionic component to improve cell preservation. In re Kerkoven (205 USPQ 1069). Therefore, then, barring unexpected results, one would reasonably expect enhanced, additive, or synergistic activity to be observed by combining the compositions or materials. Therefore claim 23 is rendered obvious as claimed.
Therefore Applicant’s Invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 01 October 2025 are acknowledged. The Applicant argues Hubel and She are silent regarding the use of a poloxamer in the claimed amount. The Applicant acknowledges Austen teaches the polymer concentration may be varied, but alleges [0006] of Austen “discourages using higher concentrations”. The Applicant argues Austen teaches using poloxamer P188 at a concentration of 5 mg/ml to 15 mg/ml compared to the broader range disclosed for polymers (1 mg/ml to 20 mg/ml). The arguments state Austen does not disclose the general conditions of the claimed composition. The Applicant argues Austen does not teach the specific combination of a poloxamer with both a sugar and sugar alcohol component in the claimed amounts. The arguments state Agulnick does not cure this deficiency.
Regarding new claim 21: The Applicant argues Austen does not teach the claimed amount of polymer recited in claim 1. The Applicant alleges Austen suggests using no more than 15 mg/ml P188 at [0048]).
Regarding new claim 22: The Applicant argues [0078] of the specification demonstrates a synergistic effect when P188 and non-essential amino acids (NEAA) are both added.
Regarding new claim 23: The Applicant states claim 23 recites Hank’s Balanced Salt Solution (HBSS). The Applicant argues the specification indicates a synergistic effect when HBSS is used with poloxamer at Example 1, [0080].
EXAMINER’S RESPONSE
The arguments are not persuasive. Claim 1 recites “poloxamer”. Poloxamers are a class of copolymers. While the Applicant argues Austen does not teach poloxamer P188 in the claimed amount, claim 1 encompasses any known poloxamer. Austen teaches other poloxymers can be used ([0008]).
A search of [0006] of Austen does not show the art “discourages using higher concentrations” of poloxamer. At [0006] Austen teaches “typically, the polymer is added to the cryopreserved cells at a concentration ranging from approximately 1 mg to approximately 20 mg of polymer per ml of cells”. Therefore the art teaches the amount is based on the volume of cells being preserved. At [0006] Austen teaches
“in certain embodiments, P188 is at a concentration of approximately 10 mg/ml”. As set forth above, this is based on the volume of cells to be preserved. At [0006] Austen teaches “typically the lowest concentration of polymer that yields the desired membrane stabilization following cryopreservation is used”. Austen teaches the concentration of polymer used needs to sufficiently stabilize the membranes of the cryopreserved cells and improve viability may vary depending on the cells, the concentration of the cells and downstream application (supra). The skilled artisan would optimize the amount of polymer based on the amount of cells being preserved. MPEP 2144.05 teaches differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. The Applicant has only provided arguments, and not evidence, the claimed amount of poloxamer is critical.
Regarding new claim 21: The arguments are not persuasive. Austen teaches P188. [0048] states the amount of P188 is “per ml” of cryopreserved cells. While [0048] states “in certain embodiments” the concentration of P188 is “15 mg of polymer per mL of cryopreserved cells”. Austen does not teach using “no more than 15 mg/ml P188” at [0048] as alleged by the Applicant. Therefore the arguments are not persuasive.
Regarding new claim 22: The Applicant argues [0078] demonstrates a synergistic effect when P188 and NEAA are both added. In response, claim 22 does not require P188. While the specification discloses specific concentrations of amino acids and 5% P188 ([0084] [0098]), claim 22 encompasses any amount of the amino acids and a broader range of poloxamer. The claims are not commensurate in scope. Therefore the arguments are not persuasive.
Regarding new claim 23: Examiner notes the claim does not recite HBSS, as alleged by the Applicant. The claim recites “an ionic component” comprising the recite salts. The Applicant argues the specification indicates a synergistic effect when HBSS is used with poloxamer. [0090] of the specification discloses an HBSS formulation comprising specific concentrations of ionic components. Claim 23 encompasses any amount of the recited ions.
The specification discloses HBSS in combination with 5% poloxamer 188. Claim 23 does not require P188. Claim 1 encompasses a range of poloxamer that is broader than 5%. Therefore it is not commensurate with the scope of the disclosure pointed to by the Applicant. Therefore the arguments are not persuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Claims 1-7, 9-17 and 21-23 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,985,969 B2 ('969; Hubel et al. Cryopreservative compositions and methods. 21 May 2024) in view of She et al. (US 2018/0092348), Hubel et al. (US 2017/0172138) and Austen et al. (US 2012/0128641). Although the conflicting claims are not identical, they are not patentably distinct from each other because the claim limitations of the Instant Application encompass claim limitations of the patent.
Regarding instant claim 1: The Hubel (‘969) Patent teaches a cryopreservative composition that contains a sugar component (0.1 to 300 mM; see claims 1-2) and a sugar alcohol component (0.1mM to 2M; see claim 1). The composition does not contain albumin or DMSO. It is noted the amounts taught in Hubel encompass the “sugar component” to “sugar alcohol component” ratio recited in instant claim 1 of the instant application (e.g., 0.1 mM sugar component and 0.1 mM sugar alcohol component). While the ‘969 patent does not explicitly claim the “sugar component” to “sugar alcohol component” ratio, this deficiency is remedied by She and Hubel (cited in the rejections below). It would have been obvious to use a sugar component and a sugar alcohol component in the claimed range of ratios. One would have been motivated to do so since She teaches a cryopreservative comprising a sugar and a sugar alcohol and Hubel teaches sugar and sugar alcohol can be used in a cryopreservative in amounts that include 1:50 to 1:1 ratios. One would have had a reasonable expectation of success since Hubel teaches the components can be included in a cryopreservative in amounts that read on the claimed range. One would have expected similar results since both references are directed to compositions used to cryopreserve cells.
While the ‘969 patent does not explicitly claim the poloxamer as claimed, this deficiency is remedied by Austen (cited in the rejections below). Austen teaches the use of the polymer, poloxymer P188 (Abstract); [0033]). Austen teaches Poloxymers are also known as poloxamers ([0005]). It would have been obvious to use a poloxamer in the composition taught by She. One would have been motivated to do so since She teaches a polymer and Austen teaches poloxamer can be used as a polymer in a medium for cryopreservation. One would have had a reasonable expectation of success using a polymer since Austen teaches polymers can be used with sugars and sugar alcohols during freezing. One would have expected similar results since both references are directed to compositions for cell cryopreservation. It would have been obvious to use a polymer in the claimed amount. One would have been motivated to do so since She teaches a polymer as a non-permeating cryoprotectant and Austen teaches polymers can be added to stabilize the cell membrane during freezing. Austen teaches the concentration ranges from approximately 1-20 mg of polymer per ml of cryopreserved cells. Austen teaches the concentration of polymer used needs to sufficiently stabilize the membranes of the cryopreserved cells and improve viability may vary depending on the polymer used, the cells, the concentration of the cells and downstream application. The skilled artisan would optimize the amount of polymer based on the amount of cells being preserved. One would have had a reasonable expectation of success using a polymer since Austen teaches polymers can be used with sugars and sugar alcohols during freezing. One would have expected similar results since both references are directed to compositions for cell cryopreservation.
Regarding claim 2: ‘969 teaches a sugar component (0.1 to 300 mM; see claims 1-2). Regarding claim 3: Claim 4 of ‘969 teaches glucose. Regarding claim 4: Claim 4 of ‘969 the cryopreservative composition of claim 1 wherein the sugar component comprises trehalose, fructose, sucrose or glucose. The ‘969 Patent discloses the sugar component is 0.1 to 300 mM. Regarding claim 5: Claim 1 of the ‘969 Patent discloses see a sugar alcohol component (0.1mM to 2M). Regarding claim 6: Claim 7 of the ‘969 Patent discloses xylitol, mannitol and inositol. Regarding claim 7: Claim 8 of the ‘969 Patent recites glycerol at a concentration of 0.6 M to 1.4 M. Regarding claim 9: The ‘969 Patent does not teach albumin, but this deficiency is cured by She. She teaches a macromolecule comprising albumin ([0038]). She teaches the composition can include about 1% (w/v) to about 10% (w/v) of the macromolecule ([0008]). This encompasses the claimed concentration of albumin. Regarding claim 11: Claim 9 of the ‘969 Patent recites amino acid a concentration of from 0.1 mM to 300 mM. Regarding claim 13: Claims 1 and 9 of the ‘969 Patent recite amino acids and peptides. Regarding claims 15 and 17: Claim 13 of the ‘969 Patent recites the cell is thawed, removed from the composition and cultured to remain viable.
Regarding claim 21: Austen teaches poloxymer P188 is used to increase the viability of cells ([0006] [0033] [0039]).
Regarding claim 22: She teaches the composition may or may not comprise one or more amino acids ([0101]). The amino acids include glycine, alanine, asparagine, aspartic acid, glutamic acid, proline and serine ([0102]).
Regarding claim 23: She teaches the components are dissolved in a balanced electrolyte solution (e.g., a saline solution) ([0061]). In one embodiment, the saline solution comprises one or more of the following: Calcium Chloride, Magnesium Sulfate, Potassium Chloride, Potassium Phosphate, Sodium Chloride, Sodium Bicarbonate ([0061]). She also teaches magnesium chloride salt ([0108]).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
APPLICANT’S ARGUMENTS
The Applicant argues neither the claims nor the specification of the’969 Patent teach 3-8% poloxamer.
In response: The rejection above acknowledges the ‘969 Patent (Hubel) does not teach a poloxamer. The Austen reference is relied upon to teach using a poloxamer in a composition for cryopreservation. Therefore this argument is not persuasive.
The Applicant acknowledges Austen teaches the use of polymers to improve the viability of cryopreserved cells. The Applicant argues Austen teaches the polymer is added to cryopreserved cells at concentrations ranging from approximately 1 mg/ml to 20 mg/ml. The Applicant argues Austen teaches when poloxamer P188 is used, the concentration is more narrowly set at about 5 mg/mL to 15 mg/ml. The Applicant argues this is lower than the claimed concentration. The Applicant alleges 1 mg/mL to 20 mg/mL corresponds to approximately 0.1 % to 2% w/v, assuming typical cell suspension densities.
In response: At [0006] Austen teaches “typically, the polymer is added to the cryopreserved cells at a concentration ranging from approximately 1 mg to approximately 20 mg of polymer per ml of cells”. Therefore the art teaches the amount is based on the volume of cells being preserved. At [0006] Austen teaches “Typically the lowest concentration of polymer that yields the desired membrane stabilization following cryopreservation is used”. Austen teaches the concentration of polymer used needs to sufficiently stabilize the membranes of the cryopreserved cells and improve viability may vary depending on the cells, the concentration of the cells and downstream application (supra). The skilled artisan would optimize the amount of polymer based on the amount of cells being preserved. MPEP 2144.05 teaches differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.
The Applicant argues 1 mg/mL to 20 mg/mL corresponds to approximately 0.1 % to 2% w/v, assuming typical cell suspension densities. The argument is based on an “assumed” cell density that is not recited in the claims or by Austen. Austen does not teach the concentration is “set” at 5 mg/mL to 15 mg/ml. Therefore this argument is not persuasive.
The Applicant argues Austen does not contemplate incorporating polymers
as component of a cryopreservative composition intended for use during freezing.
The Applicant argues Austen teaches the use of polymers for a fundamentally different purpose than that of the present application. Austen teaches that polymers are used to seal or stabilize damaged cell membranes and improve post-thaw viability. In contrast, the present application discloses incorporating a polymer component, such as poloxamer, directly into the cryopreservative composition prior to freezing to improve cryopreservation outcomes. The Applicant argues none of the references teach combining poloxamer with a sugar component and a sugar alcohol component.
In response: Contrary to Applicant’s arguments, Austen teaches the polymer can be added with a cyroprotectant, e.g. before the cells are frozen ([0039]). The cells can be frozen in the presence of one or more cryopreservative agents ([0047]). Trehalose, glucose, lactose and maltose (hence, sugars) and glycerol (hence, a sugar alcohol) are identified as cryopreservation agents by Austen ([0047]). Therefore Austen teaches poloxamers can be combined with a sugar and a sugar alcohol. The claimed amounts are rendered obvious on the grounds set forth above. The Applicant argues the claimed composition improves :cryopreservation outcome”. An “outcome” is a consequence of something. Using a poloxamer to improve post-thaw viability, as taught by Austen, is interpreted to be an improved cryopreservation outcome. Therefore the arguments are not persuasive.
CONCLUSION
No Claims Are Allowed
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.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653