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 .
1. Claims 1, 5, 18, 20, 32, 33, and 35 – 41 are pending and under consideration.
Withdrawn Claim Rejections
2. The rejection of claim 1 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendment to the claim to delete “substantially”.
3. The rejection of claim 36 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendment to the claim to delete “about”.
4. The rejection of claims 1, 5, 18, 20, 32, 33, and 35 – 37 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to claim 1 to require sodium chloride and that De Korte teaches removing sodium chloride from their storage solution in order to promote a chloride shift that would increase 2,3-DPG formation.
Duplicate Claims Warning
5. Applicant is advised that should claim 35 be found allowable, claim 41 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 35 recites: The storage solution according to claim 1, wherein the storage
solution has a pH of from about 8 to about 10.
Claim 41 recites: The pRBC storage solution according to claim 1, wherein the pRBC storage
solution has a pH of from about 8 to about 10.
Claims 35 and 41 cover the same thing despite the difference in wording of “storage solution” of claim 35 and “pRBC storage solution” of claim 41.
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.
6. Claim(s) 1, 5, 18, 20, 32, 33, and 35 – 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bitensky (US-8071282-B2; Filed 05/13/2005; Published 12/06/2011), hereinafter Bitensky as evidenced by NIH (NIH: (03/25/2025). "REJUVESOL- sodium pyruvate, inosine, adenine, sodium phosphate, dibasic, and sodium phosphate, monobasic, monohydrate solution
Citra Labs, LLC." [https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=bc06c40f-81a0-45e5-80b6-61f67d445068]. Accessed 06/30/2026), hereinafter NIH in view of Harmening (US-4112070-A; Filed 06/08/1977; Published09/05/1978; previously cited), hereinafter Harmening in view of Fisher (FISHER, RACHEL A., et al. Annals of Human Genetics 37.3 (1974): 341-353; previously cited), hereinafter Fisher in view of Pendas (Pendas, J., et al. Colloids and Surfaces A: Physicochemical and Engineering Aspects 195.1-3 (2001): 259-262; previously cited), hereinafter Pendas which is cited on the IDS filed 06/15/2023.
Regarding claims 1, 5, 35, and 38 – 41, Bitensky teaches solutions for storage of blood comprising NaH2PO4 at a concentration range of 2 – 20 mM (“(NaH2PO4) at a concentration of from about 1 mM to about 5 mM” of claim 1), NaCl at a concentration from 0 – 100 mM (“sodium chloride at a concentration of from about 25 mM to about 100 mM” of claim 1), adenine at a concentration of 0.5 – 4 mM (“adenine” of claim 1 and “wherein the adenine is present at a concentration from about 1 mM to about 5 mM” of claim 39), and dextrose at a concentration of 50 – 150 mM (“dextrose” of claim 1 and “the dextrose is present at a concentration of from about 50 mM to about 100 mM” of claim 40) at a total osmolarity of 210 – 330 (claim 38) (col. 3, lines 5 – 40; Table 1 and 3). Bitensky teaches solutions EAS61 and OFAS3 contain 2 mM adenine, 110 mM dextrose, 26 mM NaCl (“sodium chloride at a concentration of from about 25 mM to about 100 mM” of claim 1), 12 mM of NaH2PO4 where the pH of EAS61 is 8.3 (claim 35 and 41) (col. 3, lines 34 – 40; Table 3). Bitensky teaches the formulation of the solutions are free of citrate and citric acid (“wherein the storage solution is free of citrate and citric acid” of claim 1) (Table 1 – 3). Bitensky does not teach “tetrasodium pyrophosphate at a concentration of from about 10 mM to about 30 mM” of claim 1.
Regarding claim 5 and 20, Bitensky teaches adding metabolic supplement Rejuvesol containing Na phosphate dibasic (“sodium phosphate” of claim 5 and 20) and Na phosphate monobasic (col. 4, lines 3 – 17; Table 2; col. 6, lines 15 – 40; col. 7, lines 1 – 25). Rejuvesol contains sodium phosphate dibasic and sodium phosphate monobasic as evidenced by NIH (page 1, para. 1 Description; page 9, Active Ingredients).
Regarding claim 18, Bitensky teaches a method of storing packed red blood cells in EAS61 or OFAS3 with Rejuvesol for a storage duration (col. 3, lines 5 – 15 and 40 – 53; col. 6, lines 15 – 40; col. 7, lines 1 – 25; Figure 5 and 7). Bitensky does not teach “tetrasodium pyrophosphate at a concentration of from about 10 mM to about 30 mM” of claim 1.
Regarding claim 32, Bitensky teaches a suspension of red blood cells in EAS61 or OFAS3 with Rejuvesol (col. 3, lines 5 – 15 and 40 – 53; col. 6, lines 15 – 40; col. 7, lines 1 – 25; Figure 5 and 7). Bitensky does not teach “tetrasodium pyrophosphate at a concentration of from about 10 mM to about 30 mM” of claim 1.
Regarding claim 33, Bitensky teaches transfusion of the suspension of red blood cells stored in OFAS3 with Rejuvesol where hemolysis remained below 1% after storage (col. 7, lines 25 – 55; col. 8, lines 1 – 50; Table 5).
Regarding claim 36, Bitensky teaches storing red blood cells in the solution with Rejuvesol for intervals of about 45 days and about 50 days in Figure 5 (col. 6, lines 30 – 33) and for intervals of about 35 days and about 50 days in Figure 7 (col. 7, lines 15 – 17) (arrows indicate addition of Rejuvesol). Bitensky teaches stored blood expires after about 42 days (col. 1, lines 25 – 27). Therefore, it would be obvious to store the red blood cells for up to 42 days as Bitensky teaches stored blood expires after 42 days.
Regarding claim 37, Bitensky teaches the method stores the red blood cells at 4 °C (col. 3, lines 40 – 46; col. 6, lines 15 – 40; col. 7, lines 1 – 25).
Bitensky does not teach “tetrasodium pyrophosphate at a concentration of from about 10 mM to about 30 mM” of claim 1. However, Bitensky teaches the supplies of liquid blood are limited by storage and stored blood expires after about 42 days (col. 1, lines 25 – 27). Bitensky teaches expired blood cannot be used and is discarded (col. 1, lines 32 – 33). Bitensky teaches there are periodic shortages of blood that occur due to donation fluctuation, emergencies, and other factors (col. 1, lines 33 – 35). Bitensky teaches the logistics of blood supply and distribution impact the military, especially during times of combat, and remote hospitals or medical facilities (col. 1, lines 35 – 37). Bitensky teaches there is currently a need for the storage of autologous blood to avoid the significant risks of infection associated with non-autologous donor blood (col. 1, lines 37 – 40). Bitensky teaches there still remains a long-felt need for the extension of the useful shelf-life of stored liquid blood, especially for extension technology that is relatively inexpensive, easy to handle, and that provides significantly extended long-term storage (col. 1, lines 63 – 67). Bitensky teaches adding Rejuvesol to the blood storage solutions and removing oxygen allows for red blood cell storage well beyond the current 5-week limit at 4 °C with levels of 2,3-DPG and ATP that are above those found in freshly drawn blood, thus enhancing the oxygen delivery capacity of the transfused blood (col. 3, lines 50 – 57; col. 6, lines 33 – 40; Figure 5; col. 2, lines 45 – 47). Bitensky teaches a rationale for this efficacy is suggested or inferred from the fact that in the cold, earlier enzymatic steps of the glycolytic pathway are more seriously impaired than the later enzymatic steps (col. 3, lines 57 – 50). Bitensky teaches by bypassing the earlier enzymatic steps of glycolysis with the addition of metabolic intermediates that directly feed or serve as substrates for the later enzymatic steps, the storage solutions have significantly boosted the production of ATP and 2,3-DPG (col. 3, lines 60 – 64). Bitensky teaches it is known that refrigerated red blood cells shed vesicles during storage and that the storage solution with Rejuvesol in the absence of oxygen limits vesicle production (col. 7, lines 15 – 25; Figure 7; col. 2, lines 52 – 55).
Regarding “tetrasodium pyrophosphate” of claim 1, Harmening teaches a blood preservation composition to maintain 2,3-DPG levels past the third week of storage comprising a phosphate source to maintain sufficient 2,3-DPG and ATP levels suitable for transfusion where the phosphate source may be inorganic pyrophosphate (col. 3, lines 1 – 9; col. 6, lines 66 – 68; col. 7, lines 10 – 19). While Harmening teaches “inorganic pyrophosphate”, Harmening does not teach the sodium salt of pyrophosphate or a concentration of about 10 mM to about 30 mM required by claim 1. However, Harmening teaches pH regulation plays a key role in blood preservation and alkaline liquid preservatives results in generally good 2,3-DPG maintenance but ATP levels rapidly decline while acid liquid preservatives result in good ATP maintenance but 2,3-DPG levels are rapidly depleted (col. 5, lines 24 – 32). Harmening teaches the need to regulate an adequate pH range for preserved red blood cells stems from the fact that pH can modify the rate at which the numerous array of enzymes associated with glucose metabolism function (col. 5, lines 32 – 35). Harmening teaches the transfused red cell, totally depleted of 2,3-DPG can regain half the normal level within about 24 hours but this reconditioning may not be rapid enough to be effective in a severely ill patient and it is not known whether the rate of resynthesis of 2,3-DPG in the donor cells given to critically ill patients is comparable to that observed in normal recipients (col. 1, lines 62 – 68). Harmening teaches blood with nearly normal hemoglobin-oxygen affinity is thus preferable for use in massive transfusions (col. 2, lines 6 – 9). One would have been motivated to combine the teachings of Bitensky and Harmening because both teach red blood cell storage solutions to increase 2,3-DPG and ATP levels of the red blood cells to that which are suitable for transfusion.
Regarding “tetrasodium pyrophosphate” of claim 1, Fisher teaches RBCs have an inorganic pyrophosphatase that catalyzes the hydrolysis of inorganic pyrophosphate to inorganic phosphate (page 341, para. 1 and 3; page 351, para. 5). Fisher teaches tetrasodium pyrophosphate (10 mM) is a substrate for the pyrophosphatase from RBCs (page 344, para. 4 – 5; page 345, para. 1). One would have been motivated to combine the teachings of Bitensky, Harmening, and Fisher because Bitensky and Harmening teach red blood cell storage solutions and Harmening teaches inorganic pyrophosphate may be used as a metabolizable phosphate in RBC storage solutions to maintain sufficient 2,3-DPG and ATP levels suitable for transfusion and Fisher teaches tetrasodium pyrophosphate is a substrate for pyrophosphatase found in RBCs.
Regarding a concentration of tetrasodium pyrophosphate of “about 10 mM to about 30 mM” of claim 1, Pendas teaches a RBC preservation solution comprising dextrose, phosphate buffer, and 10 mM tetrasodium pyrophosphate (page 261, left col. para. 1 – 3; Figure 1; page 262, left col. para. 1 – 2). Pendas teaches the decreasing viability and in vivo survival of RBCs observed in blood bank storage are due to alterations in their rheologic properties and metabolic status (Abstract; page 259, left col. and right col. para. 1).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Bitensky regarding red blood cell storage solutions comprising NaH2PO4, sodium chloride, adenine, dextrose, and metabolic supplement that do not contain citrate or citric acid that allows for red blood cell storage well beyond the current 5-week limit at 4 °C with levels of 2,3-DPG and ATP that are above those found in freshly drawn blood, thus enhancing the oxygen delivery capacity of the transfused blood with the teachings of Harmening regarding the addition of a phosphate source that may be inorganic pyrophosphate to a red blood cell storage solution to maintain 2,3-DPG levels past the third week of storage with the teachings of Fisher regarding tetrasodium pyrophosphate is a substrate for the pyrophosphatase found in red blood cells with the teachings of Pendas regarding a red blood storage solution comprising dextrose, phosphate buffer, and 10 mM tetrasodium pyrophosphate to arrive at the claimed packed red blood cell storage solution comprising: tetrasodium pyrophosphate at a concentration of from about 10 mM to about 30 mM; one or more electrolytes comprising monosodium phosphate (NaH2PO4) at a concentration of from about 1 mM to about 5 mM; sodium chloride at a concentration of from about 25 mM to about 100 mM; adenine; and dextrose; wherein the storage solution is free of citrate and citric acid. One would have been motivated to combine the teachings of Bitensky, Harmening, Fisher, and Pendas in a packed red blood cell storage solution allowing storage of packed red blood cells that are suitable for transfusion as Bitensky teaches there still remains a long-felt need for the extension of the useful shelf-life of stored liquid blood, especially for extension technology that is relatively inexpensive, easy to handle, and that provides significantly extended long-term storage and Bitensky teaches the supplies of liquid blood are limited by storage and stored blood expires after about 42 days. Further, it would be obvious to adjust the concentration of tetrasodium pyrophosphate and NaH2PO4 since it is a result-effective variable dependent on the desired pH of the storage solution as Harmening teaches pH regulation plays a key role in blood preservation and alkaline liquid preservatives results in generally good 2,3-DPG maintenance but ATP levels rapidly decline while acid liquid preservatives result in good ATP maintenance but 2,3-DPG levels are rapidly depleted and Harmening teaches the need to regulate an adequate pH range for preserved red blood cells stems from the fact that pH can modify the rate at which the numerous array of enzymes associated with glucose metabolism function and Bitensky teaches the storage solution can have a concentration range of NaH2PO4 of 2 – 20 mM and a pH range of 5.5 – 7.7. One would have a reasonable expectation of success in combining the teachings as Bitensky teaches adding Rejuvesol to the blood storage solutions and removing oxygen allows for red blood cell storage well beyond the current 5-week limit at 4 °C with levels of 2,3-DPG and ATP that are above those found in freshly drawn blood, thus enhancing the oxygen delivery capacity of the transfused blood and Harmening teaches inorganic pyrophosphate may be the phosphate source to maintain sufficient 2,3-DPG and ATP levels suitable for transfusion and Pendas teaches a RBC storage solution comprising 10 mM tetrasodium pyrophosphate, dextrose, and phosphate buffer.
Applicant’s Arguments/ Response to Arguments
7. Applicant Argues: Applicant asserts that the PAGG-M solution of De Korte does not contain sodium chloride (as required by amended claim 1) and that the ordinary skilled artisan reading De Korte would not have been led to modify the composition of De Korte to contain sodium chloride because De Korte sought to remove sodium chloride to promote a chloride shift that would increase 2,3-DPG formation.
Response to Arguments: Applicant’s arguments regarding De Korte have been fully considered and are found persuasive. The rejection of the claims citing the teachings of De Korte have been withdrawn. In the new rejection set forth above, Bitensky teaches red blood cell storage solutions containing 26 mM sodium chloride that allows for red blood cell storage well beyond the current 5-week limit at 4 °C with levels of 2,3-DPG and ATP that are above those found in freshly drawn blood, thus enhancing the oxygen delivery capacity of the transfused blood (col. 3, lines 50 – 57; col. 6, lines 33 – 40; Figure 5; col. 2, lines 45 – 47).
Applicant Argues: Applicant asserts that the present specification demonstrates unexpected beneficial effects of storing pRBCs in a storage solution as presently claimed when compared to the citrate-containing AS-3 storage solution as demonstrated in Examples 2 – 5 and Figures 1 – 4 and 6 including reduction in microvesicle release, increased ATP content, and reduced phosphatidylserine expression.
Response to Arguments: In the new rejection set forth above, Bitensky teaches the red blood cell storage solutions are Oxygen Free Additive Solution 3 that do not contain citrate or citric acid, and that allow for red blood cell storage with levels of 2,3-DPG and ATP that are above those found in freshly drawn blood, thus enhancing the oxygen delivery capacity of the transfused blood (col. 3, lines 50 – 57; col. 6, lines 33 – 40; Figure 5; col. 2, lines 45 – 47). Bitensky teaches it is known that refrigerated red blood cells shed vesicles during storage and that the storage solutions in the absence of oxygen limits vesicle production (col. 7, lines 15 – 25; Figure 7; col. 2, lines 52 – 55). Bitensky teaches in Example 6 that the storage solutions reverses exposure of phosphatidylserine during refrigeration (col. 6, lines 50 – 67; Figure 6). Bitensky teaches post transfusion survival of stored red blood cell units showed hemolysis remained below 1% through 14 weeks of storage (col. 8, lines 44 – 55). Therefore, the effects of the claimed storage solution would be expected in view of the teachings of Bitensky.
Conclusion
No claims 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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/Z.M.B./Examiner, Art Unit 1632
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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