DETAILED ACTION
Applicant’s amendment to the claims in the Response filed on 01/20/2026 is acknowledged.
The rejection of record under 35 U.S.C. § 112(b) is withdrawn in view of Applicant’s amendment to the claims in the Response filed on 01/20/2026.
The rejection of record under 35 U.S.C. § 103 is maintained and set forth again below.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3, 6, 8, 10, 11, 13, 14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Gabrio et al. (J. Clin. Invest., 34(10):1509-1512 (1955), prior art of record, hereinafter “Gabrio”) in view of Selim et al. (Clin. Sci., 121:565-572 (2011), prior art of record, hereinafter “Selim”).
With respect to claim 1, Gabrio teaches the addition of adenosine to stored blood with the purpose of reversing storage lesion and improving maintenance of the post-transfusion viability of erythrocytes (RBCs) (Abstract). Rabbit and human blood collected in acid-citrate-dextrose (ACD) were contacted with adenosine (forming a storage composition) and stored thereafter (pg. 1509, right col., par. 4; pg. 1510, right col., par. 1). The viability of RBCs treated with adenosine showed essentially no change over the three weeks following incubation compared to the control blood, and reversal of storage lesion with adenosine was demonstrated (pg. 1511, left col., par. 2; right col. par. 4). Furthermore, at the total storage time, the post-transfusion survival of blood treated with adenosine was improved (pg. 1511, left col., par. 2). Regarding claims 10, 11, 13 and 14, Gabrio teaches contacting the RBCs with an additive that is the anti-coagulant agent acid-citrate-dextrose (ACD), in addition to adenosine (pg. 1509, section I; pg. 1510, section II). With respect to claim 16, Gabrio teaches that RBCs were contacted with adenosine during the period of storage, which lasted six weeks (the RBC, adenosine and S1P are contacted at any point during a period of storage of the RBC having a duration of about 5 weeks to about 7 weeks) (pg. 1511, left col., par. 2).
Gabrio does not teach contacting the RBC with sphingosine-1-phosphate (S1P) in addition to adenosine. However, Selim teaches a “consistent and striking decline in RBC S1P content during storage” (page 571, first column; FIG. 4). Selim further teaches that “[c]hanges in S1P content may contribute to an RBC storage lesion” (Abstract).
Selim teaches a “trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P” (Abstract). Selim teaches RBC
transfusion disrupts normal S1P homoeostasis and “that one potential source for disruption of S1P homoeostasis in transfusion recipients could be the use of RBC units with altered S1P content, particularly aged RBCs in which S1P levels have become depleted (page 571).” Selim further teaches that “[t]wo firmly established effects of circulating S1P are to maintain
endothelial barrier function and to regulate immune cell trafficking” (page 571, second column).
Selim teaches “[f]urther studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P” (Abstract). Selim teaches also teaches that “[t]he present work supports the concept that changes in the lysopholipid content of RBCs during storage could have biological and clinical ramifications. One logical extension of our findings is to investigate ways of enriching stored blood with S1P as a means to investigate the effect that restoration of circulating S1P has on clinical outcomes” (Abstract).
As such, Selim provides a clear teaching, suggestion, and motivation to add S1P to stored RBCs to offset the rapid decrease in RBC S1P levels associated with storage to prevent an RBC storage lesion and downstream complications associated with transfusion of RBCs with low S1P with a reasonable expectation of success.
At a minimum, Selim provides a clear roadmap to arrive at the claimed method since “[o]ne logical extension of [Selim’s] findings is to investigate ways of enriching stored blood with S1P as a means to investigate the effect that restoration of circulating S1P has on clinical outcomes” (page 571, second column) and instructs to “investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P” (Abstract).
Regarding claims 3 and 6, it would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal amounts of adenosine and S1P for use in the method taught by Gabrio and Selim to ensure proper storage conditions with a reasonable expectation of success. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It is noted that claim 8 only recites intended results of the method rather than requiring an additional step be performed. Since this claim only recites the results of the method, then Gabrio and Selim will also read on these results since performing the same steps will inherently lead to the same results in the absence of evidence to the contrary, including unexpected results.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Gabrio and Selim as applied to claims 1, 3, 6, 8, 10, 11, 13, 14 and 16 above, and further in view of Payrat et al. (US 2004/0106094 A1, prior art of record, hereinafter “Payrat”).
As discussed above, claims 1, 3, 6, 8, 10, 11, 13, 14 and 16 were rendered prima facie obvious by the teachings of Gabrio and Selim. Regarding claim 15, neither Gabrio nor Selim teaches a composition as claimed having a pH which has a range of about 5.0 to about 9.0.
However, Payrat discloses a solution for storing red blood cells and maintaining ATP and 2.3-BPG (abstract). Payrat discloses adjusting the solution to a physiological pH of about 7.4.
Accordingly, it would have been prima facie obvious to a person of ordinary skill in the art to perform a method of storing RBCs by using a storage composition with a pH of about 5.0 to about 9.0, e.g., 7.4, as taught by Payrat, since compositions for storing red blood cells with a pH of 7.4 were known before the effective filing date, and were recognized as being physiological, as taught by Payrat. Therefore, a person of skill in the art would have been motivated to store RBCs by formulating a composition disclosed by the combined teachings of Gabrio and Selim so that the pH is a physiological pH, such as 7.4, to provide a suitable environment to store the RBCs, mimicking the physiological conditions.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments filed 01/20/2026 have been fully considered but they are not persuasive. Applicant’s arguments are discussed to the extent they apply to the current grounds of rejection set forth above.
On pages 9-10 of the Response, Applicant urges that “Gabrio and Selim are silent regarding a storage composition including, RBC, adenosine, and sphingosine 1-phosphate (S1P).” As discussed above, Gabrio teaches a storage composition comprising RBC and adenosine. Any deficiency in Gabrio is cured by Selim, which provides a clear teaching, suggestion, and motivation to add S1P to an RBC storage composition at least by instructing one of ordinary skill in the art “to investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P” (Selim, Abstract). Selim provides a “logical extension” to one of ordinary skill in the art to add S1P to an RBC storage composition at least because Selim teaches a “consistent and striking decline in RBC S1P content during storage” and that “[c]hanges in S1P content may contribute to an RBC storage lesion” (page 571, first column; FIG. 4; Abstract). As such, the combination of Gabrio and Selim teaches a storage composition comprising RBC, adenosine, and S1P, as claimed.
On pages 10-11 of the Response, Applicant urges that “armed with Gabrio and Selim, one skilled in the art would not have had any reasonable motivation or suggestion to include the sphingosine 1-phosphate of Selim in the RBC storage composition of Gabrio so as to arrive at the present invention.”
As discussed above, Selim teaches a “consistent and striking decline in RBC S1P content during storage” (page 571, first column; FIG. 4). Selim further teaches that “[c]hanges in S1P content may contribute to an RBC storage lesion” (Abstract). Selim provides a nexus between S1P levels and RBC storage lesions. Selim further instructs one of ordinary skill in the art to “investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P” since “[t]he present work supports the concept that changes in the lysopholipid content of RBCs during storage could have biological and clinical ramifications” (Abstract). Accordingly, Selim provides a clear teaching, suggestion, and motivation to include S1P in the RBC storage composition taught by Gabrio to arrive at the present invention.
On page 11 of the Response, Applicant urges that there is “no reasonable expectation of success in combining the applied references to arrive at the features of claim 1” since “the link between adding SIP in stored RBC and solving adverse clinical events after blood transfusion proposed in Selim is highly speculative and a mere invitation for further research.”
While obviousness does require at least some degree of predictability, it does not require absolute predictability. See MPEP § 2143.02(II). Here, the prior art recognized a decline in RBC S1P content during storage and links this decline to an RBC storage lesion. As such, one of ordinary skill in the art would have had a reasonable expectation of success when combining Gabrio and Selim to improve RBC storage.
On pages 11-12 of the Response, Applicant urges that “the present application, in some non-limiting embodiments, describes that the combination of adenosine and S1P improved metabolic parameters of stored RBCs, and that such combination has synergistic effects.” To support this argument Applicant urges that “referring to Fig. 1 of the present application, adding various concentrations of only adenosine or only SIP improved RBC glycolysis (as assayed by glycolytic ratio) modestly during storage, but adding both adenosine and SIP significantly improved this parameter further,” and “referring to Fig. 5 of the present application, adding various concentrations of only adenosine (luM and less) or only SIP (all concentrations tested) had only modest effect in reducing storage lesion of the RB Cs (as assayed by hypoxanthine levels in the cellular and supernatant fractions), but adding both adenosine and SIP significantly reduced storage lesion of the RBCs.”
Applicant’s arguments concerning synergistic effects are problematic for several reasons. FIGs. 1 and 5 lack any error bars or statistical analysis to demonstrate any difference between the various parameters, or that any difference, if present, is additive compared to synergistic. Moreover, the data in FIGs. 1 and 5 are based on the results of Example 1, which utilized 10 μM of adenosine and 5 μM S1P (see Specification, as published, ¶ 0090). In contrast, instant claim 1, e.g., requires any de minis amount of S1P, and does not require the synergistic effects allegedly present in the single embodiment from the Specification. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
Applicant’s arguments concerning claim 15 in view of Gabrio, Selim, and Payrat were fully considered, but was not found persuasive for the reasons set forth above.
Conclusion
NO CLAIMS ARE ALLOWED
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS J VISONE whose telephone number is (571)270-0684. The examiner can normally be reached Monday-Thursday, 8:30 AM to 6:30 PM.
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/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672