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 ACTION
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 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.
Response to Amendments
Applicant’s amendments, corrected specification, and response filed Mar. 23, 2026 have been received and entered into the case.
Status of the Claims
Claims 13-15, 25-26, 29, 38, 49-51, 54, 57, 59-60, 70, 78, 86-88, 91 and 94-95 currently pending.
Claims 13-15, 25-26, 29, 49-51, 54, 57, 59, 70, 78, 86, and 91 are amended.
Claims 25-26, 29, 38, and 60 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 1-12, 16-24, 27-28, 30-37, 39-48, 52-53, 55-56, 58, 61-69, 71-77, 79-85, 89-90, and 92-93 are cancelled.
Claims 94 and 95 are new.
Claims 13-15, 49-51, 54, 57, 59-60, 70, 78, 86-88, 91 and 94-95 have been considered on the merits.
Specification Objections
Specification objections are withdrawn due to amendment.
Claim Objections
Claim objections are withdrawn due to amendment.
Claim Rejections - 35 USC § 112
The claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ), are withdrawn due to amendment. New claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ) have been added to address the claim amendments. New claim rejections under 35 USC § 112, (d) or fourth paragraph (pre-AIA ) have been added to address the claim amendments.
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.
Claim 59 is 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.
In claim 59, lines 1-3, the phrase “wherein the preservation composition preserves one or both of the nucleic acids or cells in the biological sample for at least 2 weeks at ambient temperature, renders the claim and its dependents indefinite, since it is unclear what structure of the composition provides the function of preserving the nucleic acids and/or cells in the biological sample for at least 2 weeks at ambient temperature. In addition, the specification does not provide any structure for this function (0147) suggesting that it is an inherent characteristic of the composition. Additionally, the limitation could be interpreted to be an intended use of the composition. For the purposes of compact prosecution, this function will be interpreted to be an inherent characteristic to the composition containing the components of claim 59.
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 15 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 15 depends from claim 13 which requires the one or more cell surface remodeling polymer to be selected from one or more poloxamer p188 or poloxamer p407. Claim 15 recites the limitation of “the one or more cell surface remodeling polymers is selected from the group consisting of a copolymer of N-vinylpyrollidone (NVP) and a boronic acid, an arginylglyclaspartic acid (RGD) tripeptide polymer derivative, mung bean phytohaemagglutinin, a poloxamer and a synthetic glycopeptide that bears repeated ligands for the mannose 6 phosphate receptor”. This limitation broadens and includes additional cell surface remodeling polymers not included in claim 15.
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 claim rejections under 35 USC § 103 are withdrawn due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
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 13-15, 49-51, 54, 57, 59, 70 and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Haj-Ahmad et al. (US 2020/0224189 A1) (ref. of record) as evidenced by Shi et al. (Neuroscience Bulletin, 2013) (ref. of record) in view of Horlitz et al. (US 2014/0227688 A1) (ref. of record) and Toner et al. (US 2022/0104482 A1, priority to Feb. 7, 2019) (ref. of record).
With respect to claims 13 and 70, Haj-Ahmad teaches a preservative composition and kit for preserving cell-free nucleic acids and/or cells (abstract, 0001 and 0009).
With respect to claim 13 (a) and (b), Haj-Ahmad teaches the preservative composition containing an osmotic agent and at least one enzyme inhibitor (0010). With respect to claim 13 (c), Haj-Ahmad teaches the preservative composition containing a volume excluding polymer that is polyethylene glycol (PEG)(0010 and 0023). PEG is a cell surface remodeling polymer as evidenced by Shi. Shi reports that polyethylene glycol (PEG) can reseal cell membranes of neurons (abstract). Haj-Ahmad teaches the volume excluding polymer which can be PEG a cell surface remodeling polymer is about 10-50% by weight of the composition (0010-0011). The range is the same as the claimed ranges of 10-50% for the cell surface remodeling polymer.
Haj-Ahmad does not teach the preservation composition where the osmotic agent is present in an amount sufficient to produce a hypertonic solution as recited in claim 13. However, Horlitz teaches a preservation solution for preserving cells and nucleic acids that is hypertonic (abstract and 0016-0017). Horlitz further teaches that hypertonic agent stabilize the cells in sample and by increasing the stability of cells reduces the release of intracellular nucleic acids (0014 and 0017). In addition, Horlitz teaches the hypertonic agent can be sucrose, glycerol, mannitol, sorbitol (0084). Accordingly, at the effect time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the preservative composition of Haj-Ahmad so that the osmotic agent is present in an amount sufficient to produce a hypertonic solution for the benefit of giving the composition the ability to further stabilize cells and nucleic acids as taught by Horlitz. It would have been obvious to one of ordinary skill in the art to make such a modification to Haj-Ahmad, since similar preservative composition used for the same purposes include osmotic agents in an amounts sufficient to produce a hypertonic solution. Furthermore, one of ordinary skill in the art would have a reasonable expectation of success in making such a modification to Haj-Ahmad, since Haj-Ahmed teaches the inclusion of an osmotic agent in a preservative composition for cells and nucleic acids, and Horlitz teaches the benefits of including osmotic agents at a concentration so that a preservative composition for cells and nucleic acids is hypertonic for the benefit of stabilizing the cells and nucleic acids.
Haj-Ahmad does not teach the preservative composition where the cell surface remodeling polymer is a poloxamer and is poloxamer p188 and/or poloxamer p407 as recited in claim 13 (c). Haj-Ahmad does not teach the preservative composition where the cell surface remodeling polymer is one of those listed in e) of claim 15. However, Toner teaches a preservation composition for cells and biological samples containing an osmotic agent and where the osmotic agent is hydroxyethyl starch (a starch and a non-protein colloid) (abstract and 0069). Toner teaches the preservation solution containing an anti-shearing agent to help reduce the stress on preserved cells where the anti-shearing agent is poloxamer 188, dextran (a non-protein colloid) or PEG (cell surface remodeling polymer) and is a concentration of 0.1 to 15% weight/volume (0068). Accordingly, it would have been obvious to one of ordinary skill in the art at the effect time of filing of the claimed invention to combine the instant ingredients for their known benefits in preservative compositions, as disclosed by Toner above, since each is well known in the art for their use in cell preservative compositions. This rejection is based on the well-established proposition of patent law that no invention resides in combining old ingredients of known properties where the results obtained thereby are no more than the additive effect of the ingredients. The idea for combining them flows logically from their having been used individually in the prior art.
Although, Toner does not teach the exact ranges recited in claim 13 for the poloxamer, the ranges overlaps with the ranges taught, one of ordinary skill in the art would recognize that the amount of poloxamer is a result effective variable and that the amount of poloxamer would be matter of routine optimization.. Additionally, Haj-Ahmad teaches the volume excluding polymer which can be PEG, a cell surface remodeling polymer, is about 10-50% by weight of the composition (0010-0011). The range is the same as the claimed ranges of 10-50% for the cell surface remodeling polymer.
With respect to claim 70, the instructions are non-limiting. Written instructions reciting an alleged novel use of a composition do not change the composition itself. See, e.g., In re Haller 73 USPQ 403, at 404 (CCPA 1947), “Accordingly, the mere labeling of an old composition as an insecticide does not make it a new or different composition within the meaning of the patent statutes”.
With respect to claim 14, Haj-Ahmad teaches the osmotic agent is present in the preservation composition in amount of about 1 to 20% by weight of the composition, and the at least one enzyme inhibitor is present in the preservation composition in amount of about 1 to 30% by weight of the composition (0010-0011). The ranges are within or the same as the claimed ranges of 1 to 30% for the osmotic agent and 1 to 30% for the enzyme inhibitor.
With respect to claim 49, Haj-Ahmad teaches a composition containing the preservation composition and a biological sample (0014-0015). With respect to claim 50, Haj-Ahmad teaches the biological sample is blood or tumor cells (0019 and 0026). With respect to claim 51, Haj-Ahmad teaches the biological sample is blood, plasma, serum, urine, saliva, stool, breast milk, tears, sweat, cerebral spinal fluid, synovial fluid, semen, vaginal fluid, ascitic fluid, amniotic fluid or ascitic fluid (0019 and 0026).
With respect to claim 54, Haj-Ahmad teaches the biological sample contains nucleic acids and where the nucleic acids are cellular or cell-free (0009 and 0020). Haj-Ahmad teaches the cell-free nucleic acids can include DNA and/or RNA (0049). It would be readily understood that the cellular nucleic acids would contain both RNA and DNA. With respect to claim 57, Haj-Ahmad teaches the ratio of preservative composition to the biological sample is about 1:10 to 1:1 and preferably about 1:5 to 1:4 (0089). With respect to claim 59, Haj-Ahmad teaches the composition can preserve the nucleic acids for at least 28 days at room temperature (0053).
Haj-Ahmad does not teach that kit further contains a blood or other biological sample collection tube containing an predetermined amount of an anticoagulant as recited in claim 78. Additionally, Haj-Ahmad does not teach that kit further containing a syringe or a needle attachable to the syringe as recited in claim 78.
However, Toner teaches a kit for preserving cells containing the preservation solution, a container for collecting blood with anti-coagulant (the amount would inherently have to be predetermined) a syringe and a needle (0037, 0096 and claim 71). In addition, Toner teaches an example where syringe with a needle and containing preservation solution is used in combination with a blood collection tube (0105). Further with respect to the instructions of claim 70, which are consider non-limiting, Toner teaches the kit containing a set of instructions (0037). In further support, Shinko teaches a kit for preserving cells containing the preservation solution, a syringe containing a concentrated form of the supplement (preservation composition) and instructions for use of the preservative composition (0145-0146). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the kit of Haj-Ahmed to include a blood or other biological sample collection tube containing an predetermined amount of an anticoagulant, a syringe and a needle attachable to the syringe for the benefit and convenience of having all of the necessary components in a single packet for collecting a sample to be preserved using the preservative composition. It would have been obvious to include the claimed components of the kits of claim 78 in the kit of Haj-Ahmed, since these were known to be included in similar kits for preserving samples of cells and nucleic acids as taught by Toner and Shinko. For these reasons, one of ordinary skill in art would have had a reasonable expectation of success in making such a modification to the kit of Haj-Ahmed.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 15, 94 and 95 is rejected under 35 U.S.C. 103(a) as being unpatentable over Haj-Ahmad as evidenced by Shi in view of Horlitz and Toner (as applied to claims 13-15, 49-51, 54, 57, 59, 70 and 78 above), and further in view of Shimko et al. (US 2009/0017439 A1) (ref. of record).
The teachings of Hau-Ahmad, Horlitz, and Toner can be found in the previous rejection above.
With respect to claim 15, Haj-Ahmad teaches the osmotic agent is NaCl (sodium containing solution) and the enzyme inhibitor is EDTA (0012).
Haj-Ahmad does not teach the preservative composition where the osmotic agent is a potassium, magnesium or calcium containing solution, Ringer’s lactate, sorbitol, mannitol, or sucrose as recited in a) of claim 15. Haj-Ahmad does not teach the preservative composition where the enzyme inhibitor is tartaric acid and/or glucaric acid as recited in b) of claim 15. Haj-Ahmad does not teach the preservative composition further containing a plasma expander which is starch, a protein colloid or a non-protein colloid as recited in claims 94 and 95.
However, Shimko teaches a similar composition for preserving cells (abstract). With respect to a) of claim 15, Shimko teaches the composition further containing salts including sodium, potassium, magnesium or calcium (osmotic agents), additional osmotic agents and Ringer’s lactate (0068, 0088, 0090 and 0159). Shimko teaches the composition further containing additional agents including sorbitol, mannitol, and sucrose (osmotic agents) (0088, 0090 and 0099). With respect to b) of claim 15, Shimko teaches the composition further containing organic acids including tartaric acid (0088, 0090 and 0099). With respect to claims 94 and 95, Shimko teaches the composition further containing albumin (protein colloid), dextrans and trehalose (non-protein colloids), and starches, and hydroxyethyl starch (0091 and 0140).
Accordingly, it would have been obvious to one of ordinary skill in the art at the effect time of filing of the claimed invention to combine the instant ingredients for their known benefits in preservative compositions, as disclosed by Shimko above, since each is well known in the art for their use in cell preservative compositions. This rejection is based on the well-established proposition of patent law that no invention resides in combining old ingredients of known properties where the results obtained thereby are no more than the additive effect of the ingredients. The idea for combining them flows logically from their having been used individually in the prior art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 15 is rejected under 35 U.S.C. 103(a) as being unpatentable over Haj-Ahmad as evidenced by Shi in view of Horlitz and Toner (as applied to claims 13-15, 49-51, 54, 57, 59, 70 and 78 above), and further in view of Dorn (US 6,716,632 B1) (ref. of record).
The teachings of Hau-Ahmad, Horlitz, and Toner can be found in the previous rejection above.
With respect to c) of claim 15, Haj-Ahmad teaches the preservative composition containing a metabolic inhibitor (0013). Haj-Ahmad does not teach the preservative composition where the metabolic inhibitor is thimerosal, sodium azide and/or a chlorohexidine.
However, Dorn teaches a preservative composition for preserving patient specimens and the specimens contain cells (abstract, Col. 1 lines 10-12 and 48-51, and Col. 8 lines 19-23). In addition, Dorn teaches a preservative composition containing chlorhexidine as a microbial contamination (Col. 4 lines 25-37). Dorn reports that thimerosal has been used preservative and effectively stabilizes urine samples (Col. 2 lines 57-61). Dorn teaches that these preservatives are often added to increase shelf-life and to reduce the possibility of microbial contamination (Col. 3 lines 56-58).
Accordingly, it would have been obvious to one of ordinary skill in the art at the effect time of filing of the claimed invention to combine the instant ingredients for their known benefits in preservative compositions, as disclosed by Dorn above, since each is well known in the art for their use in cell preservative compositions. This rejection is based on the well-established proposition of patent law that no invention resides in combining old ingredients of known properties where the results obtained thereby are no more than the additive effect of the ingredients. The idea for combining them flows logically from their having been used individually in the prior art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 13-15, 49-51, 54, 57, 59, 70, 78, 86-88, 91, 94 and 95 are rejected under 35 U.S.C. 103 as being unpatentable over Haj-Ahmad et al. (US 2020/0224189 A1) (ref. of record) as evidenced by Shi et al. (Neuroscience Bulletin, 2013) (ref. of record) in view of Horlitz et al. (US 2014/0227688 A1) (ref. of record), Shimko et al. (US 2009/0017439 A1) (ref. of record), Toner et al. (US 2022/0104482 A1, priority to Feb. 7, 2019) (ref. of record), and Haj-Ahmed et al. (WO 2017/201612 A1) (Haj-Ahmed WO ‘612) (ref. of record).
With respect to claims 13, 70, 78 and 86, Haj-Ahmad teaches a preservative composition and kit for preserving cell-free nucleic acids and/or cells (abstract, 0001 and 0009).
With respect to claim 13 (a) and (b), Haj-Ahmad teaches the preservative composition containing an osmotic agent and at least one enzyme inhibitor (0010). With respect to claim 13 (c), Haj-Ahmad teaches the preservative composition containing a volume excluding polymer that is polyethylene glycol (PEG)(0010 and 0023). PEG is a cell surface remodeling polymer as evidenced by Shi. Shi reports that polyethylene glycol (PEG) can reseal cell membranes of neurons (abstract). Haj-Ahmad teaches the volume excluding polymer which can be PEG a cell surface remodeling polymer is about 10-50% by weight of the composition (0010-0011). The range is the same as the claimed ranges of 10-50% for the cell surface remodeling polymer.
Haj-Ahmad does not teach the preservation composition where the osmotic agent is present in an amount sufficient to produce a hypertonic solution as recited in claim 13. However, Horlitz teaches a preservation solution for preserving cells and nucleic acids that is hypertonic (abstract and 0016-0017). Horlitz further teaches that hypertonic agent stabilize the cells in sample and by increasing the stability of cells reduces the release of intracellular nucleic acids (0014 and 0017). In addition, Horlitz teaches the hypertonic agent can be sucrose, glycerol, mannitol, sorbitol (0084). Accordingly, at the effect time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the preservative composition of Haj-Ahmad so that the osmotic agent is present in an amount sufficient to produce a hypertonic solution for the benefit of giving the composition the ability to further stabilize cells and nucleic acids as taught by Horlitz. It would have been obvious to one of ordinary skill in the art to make such a modification to Haj-Ahmad, since similar preservative composition used for the same purposes include osmotic agents in an amounts sufficient to produce a hypertonic solution. Furthermore, one of ordinary skill in the art would have a reasonable expectation of success in making such a modification to Haj-Ahmad, since Haj-Ahmed teaches the inclusion of an osmotic agent in a preservative composition for cells and nucleic acids, and Horlitz teaches the benefits of including osmotic agents at a concentration so that a preservative composition for cells and nucleic acids is hypertonic for the benefit of stabilizing the cells and nucleic acids.
Haj-Ahmad does not teach the preservative composition where the cell surface remodeling polymer is a poloxamer and is poloxamer p188 and/or poloxamer p407 as recited in claim 13 (c). Haj-Ahmad does not teach the preservative composition where the cell surface remodeling polymer is one of those listed in e) of claim 15. However, Toner teaches a preservation composition for cells and biological samples containing an osmotic agent and where the osmotic agent is hydroxyethyl starch (a starch and a non-protein colloid) (abstract and 0069). Toner teaches the preservation solution containing an anti-shearing agent to help reduce the stress on preserved cells where the anti-shearing agent is poloxamer 188, dextran (a non-protein colloid) or PEG (cell surface remodeling polymer) and is a concentration of 0.1 to 15% weight/volume (0068). Accordingly, it would have been obvious to one of ordinary skill in the art at the effect time of filing of the claimed invention to combine the instant ingredients for their known benefits in preservative compositions, as disclosed by Toner above, since each is well known in the art for their use in cell preservative compositions. This rejection is based on the well-established proposition of patent law that no invention resides in combining old ingredients of known properties where the results obtained thereby are no more than the additive effect of the ingredients. The idea for combining them flows logically from their having been used individually in the prior art.
Although, Toner does not teach the exact ranges recited in claim 13 for the poloxamer, the ranges overlaps with the ranges taught, one of ordinary skill in the art would recognize that the amount of poloxamer is a result effective variable and that the amount of poloxamer would be matter of routine optimization.. Additionally, Haj-Ahmad teaches the volume excluding polymer which can be PEG, a cell surface remodeling polymer, is about 10-50% by weight of the composition (0010-0011). The range is the same as the claimed ranges of 10-50% for the cell surface remodeling polymer.
With respect to claim 70, the instructions are non-limiting. Written instructions reciting an alleged novel use of a composition do not change the composition itself. See, e.g., In re Haller 73 USPQ 403, at 404 (CCPA 1947), “Accordingly, the mere labeling of an old composition as an insecticide does not make it a new or different composition within the meaning of the patent statutes”.
Haj-Ahmad does not teach that kit further contains a blood or other biological sample collection tube containing an predetermined amount of an anticoagulant as recited in claims 78 and 86. Additionally, Haj-Ahmad does not teach that kit further containing a syringe or a needle attachable to the syringe as recited in claim 78.
However, Toner teaches a kit for preserving cells containing the preservation solution, a container for collecting blood with anti-coagulant (the amount would inherently have to be predetermined) a syringe and a needle (0037, 0096 and claim 71). In addition, Toner teaches an example where syringe with a needle and containing preservation solution is used in combination with a blood collection tube (0105). Further with respect to the instructions of claim 70, which are consider non-limiting, Toner teaches the kit containing a set of instructions (0037). In further support, Shinko teaches a kit for preserving cells containing the preservation solution, a syringe containing a concentrated form of the supplement (preservation composition) and instructions for use of the preservative composition (0145-0146). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the kit of Haj-Ahmed to include a blood or other biological sample collection tube containing an predetermined amount of an anticoagulant, a syringe and a needle attachable to the syringe for the benefit and convenience of having all of the necessary components in a single packet for collecting a sample to be preserved using the preservative composition. It would have been obvious to include the claimed components of the kits of claim 78 in the kit of Haj-Ahmed, since these were known to be included in similar kits for preserving samples of cells and nucleic acids as taught by Toner and Shinko. For these reasons, one of ordinary skill in art would have had a reasonable expectation of success in making such a modification to the kit of Haj-Ahmed.
Haj-Ahmad, Toner and Shinko do not teach that kit further contains a sealed ampule, containing a predetermined amount of the preservative composition where the ampule has a removable closure that is replaceable by a dispensing means as recited in claim 86. However, Haj-Ahmed WO ‘612 teaches a preservation composition for preserving nucleic acids and/or cells where the preservation composition is in a ampule (one of ordinary skill in the art would readily recognize that ampules are generally sealed) or in a syringe (0065-0067). Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the kit taught by the combined teachings of Haj-Ahmed, Toner and Shinko to further include a sealed ampule, containing a predetermined amount of the preservative composition where the ampule has a removable closure that is replaceable by a dispensing means for the benefit and convenience of having the preservative composition in an appropriate amount in a sealed container. It would have been obvious to include such an ampule in the kit taught by the combined teachings of Haj-Ahmed, Toner and Shinko, since ampules were known to be included in similar kits to contain the preservation composition as taught by Haj-Ahmed WO ‘612. For these reasons, one of ordinary skill in art would have had a reasonable expectation of success in making such a modification to the kit taught by the combined teachings of Haj-Ahmed, Toner and Shinko.
With respect to claim 14, Haj-Ahmad teaches the osmotic agent is present in the preservation composition in amount of about 1 to 20% by weight of the composition, and the at least one enzyme inhibitor is present in the preservation composition in amount of about 1 to 30% by weight of the composition (0010-0011). The ranges are within or the same as the claimed ranges of 1 to 30% for the osmotic agent and 1 to 30% for the enzyme inhibitor.
With respect to claim 15, Haj-Ahmad teaches the osmotic agent is NaCl (sodium containing solution) and the enzyme inhibitor is EDTA (0012).
Haj-Ahmad does not teach the preservative composition where the osmotic agent is a potassium, magnesium or calcium containing solution, Ringer’s lactate, sorbitol, mannitol, or sucrose as recited in a) of claim 15. Haj-Ahmad does not teach the preservative composition where the enzyme inhibitor is tartaric acid and/or glucaric acid as recited in b) of claim 15. Haj-Ahmad does not teach the preservative composition further containing a plasma expander which is starch, a protein colloid or a non-protein colloid as recited in claims 94 and 95.
However, Shimko teaches a similar composition for preserving cells (abstract). With respect to a) of claim 15, Shimko teaches the composition further containing salts including sodium, potassium, magnesium or calcium (osmotic agents), additional osmotic agents and Ringer’s lactate (0068, 0088, 0090 and 0159). Shimko teaches the composition further containing additional agents including sorbitol, mannitol, and sucrose (osmotic agents) (0088, 0090 and 0099). With respect to b) of claim 15, Shimko teaches the composition further containing organic acids including tartaric acid (0088, 0090 and 0099). With respect to claims 94 and 95, Shimko teaches the composition further containing albumin (protein colloid), dextrans and trehalose (non-protein colloids), and starches, and hydroxyethyl starch (0091 and 0140).
Accordingly, it would have been obvious to one of ordinary skill in the art at the effect time of filing of the claimed invention to combine the instant ingredients for their known benefits in preservative compositions, as disclosed by Shimko above, since each is well known in the art for their use in cell preservative compositions. This rejection is based on the well-established proposition of patent law that no invention resides in combining old ingredients of known properties where the results obtained thereby are no more than the additive effect of the ingredients. The idea for combining them flows logically from their having been used individually in the prior art.
With respect to claim 49, Haj-Ahmad teaches a composition containing the preservation composition and a biological sample (0014-0015). With respect to claims 50 and 87, Haj-Ahmad teaches the biological sample is blood or tumor cells (0019 and 0026). With respect to claims 51 and 88, Haj-Ahmad teaches the biological sample is blood, plasma, serum, urine, saliva, stool, breast milk, tears, sweat, cerebral spinal fluid, synovial fluid, semen, vaginal fluid, ascitic fluid, amniotic fluid or ascitic fluid (0019 and 0026).
With respect to claims 54 and 91, Haj-Ahmad teaches the biological sample contains nucleic acids and where the nucleic acids are cellular or cell-free (0009 and 0020). Haj-Ahmad teaches the cell-free nucleic acids can include DNA and/or RNA (0049). It would be readily understood that the cellular nucleic acids would contain both RNA and DNA. With respect to claim 57, Haj-Ahmad teaches the ratio of preservative composition to the biological sample is about 1:10 to 1:1 and preferably about 1:5 to 1:4 (0089). With respect to claim 59, Haj-Ahmad teaches the composition can preserve the nucleic acids for at least 28 days at room temperature (0053).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Mar. 23, 2026 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that there is significant unpredictability associated with preservation solutions (Remarks pg. 12 para. 4). However, this argument was not found to be persuasive, since the art teach the claimed composition and no evidence was provided to support the idea that there is significant unpredictability associated with preservation solutions.
Applicant argues that the cited references do not teach all of the limitations of the claimed inventions. Specifically, applicant argues that Haj-Ahmad does not teach a preservative composition containing one or more cell surface remodeling polymers which is poloxamer p188 or poloxamer p407 and the deficiencies of Haj-Ahmad are not remedy by the other cited references (Remarks pg. 13 para. 3-4). Applicant further argues that there is no motivation to arrive at the claimed invention since Haj-Ahmad does not teach a preservative composition containing one or more cell surface remodeling polymers which is poloxamer p188 or poloxamer p407 and the deficiencies of Haj-Ahmad are not remedy by the other cited references (Remarks pg. 14 para. 2). Applicant argues one of ordinary skill in the art would not have had a reasonable expectation of success based on the teachings of Haj-Ahmad, Shi and Horlitz (Remarks pg. 14 para. 3-4). However, these arguments were not found to be persuasive, since Toner is being relied upon for the teaching of poloxamers an poloxamer 188 in cryopreservation solutions. As explained in the rejections, one would be motivated to include a poloxamer including poloxamer 188 in the cryopreservation solution of Haj-Ahmad for its known benefit of reducing shear and stress on the cell as taught by Toner. Additionally, one would have a reasonable expectation of success in making such a modification to Haj-Ahmad, since poloxamers were known components of cryopreservation solution. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant addressed each prior art reference separately and only with regard to the specific limitations of that reference. However, when the prior art references are taken as a whole, they teach that the skilled artisan knows each step of the method as currently claimed.
Applicant argues that the deficiencies of Haj-Ahmad are not remedy by Shi, Horlitz, Shimko and Toner, since none of these references teach the claimed cryopreservation composition (Remarks pg. 15 para. 3 to pg. 16 para. 1). However, this argument was not found to be persuasive, since the arguments with respect to the rejections over Haj-Ahmad were not found to be persuasive as explained above.
Applicant further argues that there is no motivation to arrive at the claimed invention since Haj-Ahmad does not teach a preservative composition containing one or more cell surface remodeling polymers which is poloxamer p188 or poloxamer p407 and Toner teaches p188 at concentrations that are 60 times lower than those recited in claim 13 (Remarks pg. 16 para. 2). However, these arguments were not found to be persuasive, since Haj-Ahmad teaches a cryopreservation solution with a cell surface remodeling polymer (PEG) with the same concentration range of 10-50% and the range taught by Toner of 0.1 to 15% overlaps with the claimed range. Furthermore one of ordinary skill in the art would recognize the concentration of the different components including the cell surface remodeling polymer are result effect variable and would be routinely optimized depending on the conditions and cell types being used in the cryopreservation composition.
Applicant argues one of ordinary skill in the art would not have had a reasonable expectation of success based on the teachings of Haj-Ahmad, Shi, Horlitz, Shimko or Toner to arrive at the preservation composition of claim 13 (Remarks pg. 16 para. 4). However, this argument was not found to be persuasive, since the cited references teach the components of the claimed cryopreservation composition as components in cryopreservation solutions. It is maintained combining known components in cryopreservation solution would be expected to have a reasonable expectation of success, since they are known for such.
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 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.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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