DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/08/2025 has been entered.
Claims 19, 22, 23, 28, 30, 33-36, 38, 41 and 43-51 are pending in this application and were examined on their merits.
The rejection of Claims 19, 22-23, 28, 30, 33-36, 38, 41 and 43-47 under pre-AIA 35 U.S.C. 103(a) as obvious over Yoshida et al. (2007, Vox Sanguinis, 92, 22-31) in view of Turecek et al. (2001, WO2001010470A10), Bitensky (2000, U.S. Patent 6,162,396; of record in IDS filed 2/28/2019) and Smith et al. (U.S. PGPUB 20030109847; reference A), has been withdrawn.
The rejection of Claims 19, 22-23, 28, 30, 33-36, 38, 41 and 43-47 under pre-AIA 35 U.S.C. 103(a) as obvious over Fuchs et al. (1988, J. Exp. Biol., 457-477) in view of Turecek et al. (2001, WO2001010470A1), Bitensky (2000, U.S. Patent 6,162,396), Yoshida (2008, Transfusion, 48: 2096-2105) and Smith et al. (U.S. PGPUB 20030109847), has been withdrawn.
Claim Interpretation
Claim 49 contains an optional limitation. The broadest, reasonable interpretation of the limitation is that it is not required to occur and the Examiner has interpreted the claim thusly.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 21 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.
Claim 43 is rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 43 recites, “the ATP level”. It is unclear whether the limitation refers to the ATP level in the stored oxygen and carbon dioxide depleted, leukocyte depleted human packed red blood cells after three weeks of storage, an ATP level in a non-oxygen and carbon dioxide depleted, leukocyte depleted human red packed red blood composition cells having been stored in an oxygen- and carbon dioxide-impermeable storage container for three weeks at 1 to 6°C, or both. For purposes, of examination the Examiner has interpreted the limitation as being drawn only to the ATP level in the stored oxygen and carbon dioxide depleted, leukocyte-depleted human packed red blood cells after three weeks of storage (at 1 to 6°C).
The respective terms “higher than” in Claim 28, “improved oxygen transfer” in Claim 44 and “improves transfusion recovery” in Claim 51 are relative terms which render the claims indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
For example, Claim 28 refers to an ATP “level” which is an undefined value as opposed to a concentration or amount. Similarly, the recitation of “improved” and “improves” are also undefined such that the ordinary artisan would not be aware of what degree of oxygen transfer and transfusion recovery meet the limitations. Thus, the ordinary artisan could no readily ascertain the metes and bounds of the claims. For purposes of examination, the Examiner has respectively interpreted the claims as: any amount of ATP greater than control, any amount of oxygen transfer greater than control and any amount of transfusion recovery greater than control as meeting the claimed limitations.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 19, 28, 30, 33-35, 43, 44, 45, 46, 48 and 51 are rejected under pre-AIA 35 U.S.C. § 102(b) as being anticipated by Yoshida et al. (2008), of record, as evidenced by Yoshida et al. (2006), of record, Midland (2026) and Raja et al. (2008).
Yoshida et al. (2008) teaches a method comprising: providing leukoreduced whole blood cells which are soft-spun to provide a packed RBC unit which is then treated with Argon gas and placing/transferring the treated blood in a plastic anaerobic (oxygen and carbon dioxide impermeable) canister filled with hydrogen-Argon with a Pd catalyst (Pg. 2097, Column 1, Lines 20-31),
wherein the RBC comprise an acidified additive solution (AS65) having a pH of 6.5 (Pg. 2097, Column 1, Lines 40-48 and Table 1),
and storing the RBC in the plastic anaerobic canister at 1-6 °C for at least 3 weeks (Pg. 2097, Column 1, Lines 34-35 and 37-40 and Pg. 2100, Fig. 2),
and wherein the stored anerobic AS65 RBC have a mean 2,3-DPG level of about 7.0 µmol/gHb after 21 days (which is encompassed by the claimed range of 6.2 ± 3.0 µmol/gHb) and a control stored aerobic AS65 RBC have a mean 2,3-DPG level of about 1.0 µmol/gHb after 21 days (Pg. 2100, Fig. 2), and reading on Claims 19 and 30.
With regard to Claim 19, it is noted that Yoshida et al. (2008), cites Yoshida et al. (2006) for the methodology for establishing the stored anerobic AS65 RBC comprising the steps of: providing filtered ultra-pure (e.g. 100%) Argon gas through a sterilely connected 0.22 µm filter into a bag comprising the red blood cells, gently mixing for 10 minutes, expressing out the Argon gas through the filter, and repeating this process six times prior to storage in a canister filled with H2/Argon gas mixture in the presence of a Pd catalyst to deplete said red blood cell sample of both oxygen and CO2 gas (see Yoshida, [2006], Pg. 23, Column 2, Lines 24-34).
The Examiner further notes the instantly claimed product is also made by the steps of filtering Argon gas through a sterilely connected 0.22 µm filter into a bag comprising the red blood cells, gently mixing for 10 minutes, expressing out the Argon gas through the filter, and repeating this process seven prior to storage in a canister filled with H2/Argon gas mixture in the presence of a Pd catalyst to deplete said red blood cell sample of both oxygen and CO2 gas and yield an initial pCO2 of about 5 mmHg and pO2 of about 10mmHg (see Pg. 14, Paragraph [00022], Example 1 in the instant specification as filed). Thus, the prior art blood product would also be expected to be depleted of both oxygen and carbon dioxide and have a pre-storage oxygen level of 10 mmHg or less and a pre-storage carbon dioxide level of 5 mmHg or less.
With regard to Claim 28, Yoshida et al. (2008) teaches that the stored anaerobic AS65 RBC has a greater ATP level than control aerobic stored AS65 RBC after 21 days (Pg. 2100, Fig. 2A).
With regard to Claim 33, Yoshida et al. (2008) teaches that AS65 solution comprises NaCl (e.g. saline) (Pg. 2097, Table 1).
With regard to Claim 34, Yoshida et al. (2008) teaches that AS65 solution comprises the nutrient adenine (Pg. 2097, Table 1).
With regard to Claim 35, Yoshida et al. (2008) teaches that AS65 solution comprises the anticoagulant citrate-phosphate-dextrose (Pg. 2097, Table 1).
With regard to Claim 43, Yoshida et al. (2008) teaches that the ATP level after 21 days of storage is about 5.8 µmol/g Hb which is sufficiently close to the upper limit of the claimed range of 5.6 µmol/g Hb to render the value prima facie obvious. See the MPEP at 2144.05, I.
With regard to the limitations of Claim 44, wherein the stored anaerobic AS65 RBC provides improved oxygen transfer to the tissues of a patient in need thereof following transfusion as compared to a stored aerobic AS65 RBC, the Examiner notes that the claim is not a method step and does not actually require transfusion of the stored anaerobic AS65 RBC. Thus, the limitation is a functional limitation which would be inherent in the prior art composition as the prior art composition is the same as the claimed composition and would therefore be expected to have the same functional characteristics when in use. See the MPEP at 2114, I.
With regard to Claims 45 and 46, Yoshida et al. (2008), cites Yoshida et al. (2007) for the methodology for establishing anaerobic RBC conditions (Pg. 2097, Column 1, Lines 24-26) and Yoshida et al. (2007) indicates that the RBC were stored in vented anaerobic chambers by Difco (Pg. 23, Column 2, Lines 30-34). Midland (2026) evidences that Difco vented anaerobic chambers are jars. These anaerobic jars would be “capable” of being centrifuged and sterilized.
With regard to Claims 19 and 48, Raja et al. evidences that soft spin treatment of whole blood separates the blood into an RBC layer (thereby packing the RBC), an acellular plasma layer and an intermediate platelet rich plasma layer (Pg. 44, Column 1, #2). As Yoshida et al. (2008) processes whole blood by soft spin to prepare RBC units, the RBC units of Yoshida et al. (2008) would be depleted of platelets.
With regard to the limitations of Claim 51, wherein the stored anaerobic AS65 RBC provides improves transfusion recovery in a patient in need thereof following transfusion as compared to a stored aerobic AS65 RBC, the Examiner notes that the claim is not a method step and does not actually require transfusion of the stored anaerobic AS65 RBC. Thus, the limitation is a functional limitation which would be inherent in the prior art composition as the prior art composition is the same as the claimed composition and would therefore be expected to have the same functional characteristics when in use. See the MPEP at 2114, I.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 19, 22, 23, 28, 30, 33-35, 36, 43, 44, 45, 46, 48 and 51 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Yoshida et al. (2008), of record, as evidenced by Yoshida et al. (2006), of record, Midland (2026) and Raja et al. (2008).
The teachings of Yoshida et al. (2008) were discussed above.
Yoshida et al. did not teach wherein the stored anerobic AS65 RBC has a hemolysis level of less than 0.2% after 3 weeks of storage, as required by Claim 22;
wherein the stored anerobic AS65 RBC has a hemolysis level of less than 0.3% after 7 weeks of storage, as required by Claim 23;
or wherein the stored anerobic AS65 RBC has about 60% greater 2,3-DPG level compared to a stored aerobic AS65 RBC, as required by Claim 36.
While the reference listed above does not specifically teach the limitations of the % hemolysis level of the stored anerobic AS65 RBC after 3 or 7 weeks or the % by which the stored anerobic AS65 RBC 2,3-DPG is greater as compared to a stored aerobic AS65 RBC, one of ordinary skill in the art would recognize that the percentage of hemolysis in stored anerobic AS65 RBC over time and the percent by which the 2,3-DPG level is greater than control are result-effective optimizable variables. Yoshida et al. teaches that stored anerobic AS65 RBC has a hemolysis % of 0.50 ± 0.09 after 42 days (6 weeks) and wherein stored anerobic AS65 RBC has a greater 2,3-DPG level compared to a stored aerobic AS65 RBC.
This is motivation for someone of ordinary skill in the art to practice or test the parameter values widely to find those that are functional or optimal and contain the lowest percent hemolysis over time and highest 2,3-DPG % compared to control which then would be inclusive or cover that values as instantly claimed. Absent any teaching of criticality by the Applicant concerning the percentage of hemolysis over a particular period of time and the percentage of 2,3-DPG by which the composition is greater than a control composition, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are optimizable variables which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B).
Claims 19, 22, 23, 28, 30, 33-36, 38, 43, 44, 45, 46, 48 and 51 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Yoshida et al. (2008), of record, as evidenced by Yoshida et al. (2006), of record, Midland (2026) and Raja et al. (2008), as applied to Claims 19, 22, 23, 28, 30, 33-36, 43, 44, 45, 46, 48 and 51 above, and further in view of Yoshida et al. (2009).
The teachings of Yoshida et al. (2008) were discussed above.
Yoshida et al. (2008) did not teach wherein the additive solution is AS3 or OF AS3, as required by Claim 38.
Yoshida et al. (2009) teaches that stored anaerobic RBC in OFAS3 (pH 6.5) have superior recovery after 6 weeks of storage as compared to control and equivalent recover after 9 weeks of storage with no change in live span (Pg. 458, Abstract and Pg. 459, Table 1).
It would have been obvious to those of ordinary skill in the art before the instant invention to modify the method of Yoshida et al. (2008) of preparing stored anaerobic RBC comprising an acidified additive solution (AS65) to substitute the acidified additive OFAS3 solution of Yoshida et al. (2009) because both components were known in the art as acidified additive solutions for use in preparing stored anaerobic RBC and those of ordinary skill in the art could have reasonably substituted one known acidified additive solution for the other and predictably obtained stored anaerobic RBC. See the MPEP citing KSR at 2143, I., B. Those of ordinary skill in the art would have been motivated to make this substitution because Yoshida et al. (2009) teaches that OFAS3 demonstrated superior recovery even after 9 weeks of storage with no change in life span. There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, the preparation and anaerobic storage of RBC with an acidified additive solution.
Claims 19, 22, 23, 28, 30, 33-36, 41, 43, 44, 45, 46, 47, 48 and 51 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Yoshida et al. (2008), of record, as evidenced by Yoshida et al. (2006), of record, Midland (2026) and Raja et al. (2008), as applied to Claims 19, 22, 23, 28, 30, 33-36, 43, 44, 48 and 51 above, and further in view of Smith et al. (US 2003/0109847 A1), of record.
The teachings of Yoshida et al. (2008) were discussed above.
Yoshida et al. (2008) did not teach wherein the anerobic storage container comprises layers of ethylene vinyl alcohol copolymer and modified ethylene vinyl acetate copolymer, as required by Claim 41;
or wherein the anerobic storage container is enclosed within an oxygen and carbon dioxide impermeable over bag, as required by Claim 47.
Smith et al. teaches a container for storage of a therapeutic fluid, including blood, that are susceptible to deterioration on exposure to oxygen and carbon dioxide gases, wherein said container is impermeable to oxygen and carbon dioxide gases, and said container is a pouch or bag as shown in Figure 1, wherein the container comprises layers of ethylene vinyl alcohol copolymer and modified ethylene vinyl acetate copolymer (Pg. 6, Paragraph [0068]).
It would have been obvious to those of ordinary skill in the art before the instant invention to modify the method of Yoshida et al. (2008) of preparing stored anaerobic RBC wherein the composition is stored in a rigid anaerobic jar to use the anaerobic pouch or bag container comprised of multiple polymer layers of Smith et al. because both containers are used for the same purpose of storage of a therapeutic fluid, including blood, that are susceptible to deterioration on exposure to oxygen and carbon dioxide gases. Those of ordinary skill in the art would have been motivated to make this modification because the soft anaerobic container of Smith et al. would allow some flexibility in storage in irregular spaces, potentially lighter weight and portability.
There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, the anaerobic storage of oxygen and carbon dioxide susceptible fluids.
It would have been further obvious to those of ordinary skill in the art before the instant invention to modify the method of Yoshida et al. (2008) of preparing stored anaerobic RBC wherein the composition is stored in an anaerobic jar to store the stored anaerobic RBC container in an anaerobic overbag such as the container of Smith et al. because this would provide double the protection against oxygen and/or carbon dioxide ingress to the stored anaerobic RBC. Those of ordinary skill in the art would have been motivated to make this modification because this would doubly prevent contact by the stored anaerobic RBC with oxygen and/or carbon dioxide.
There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, the anaerobic storage of oxygen and carbon dioxide susceptible fluids.
Claims 19, 22, 23, 28, 30, 33-36, 43, 44, 45, 46, 48, 49 and 51 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Yoshida et al. (2008), of record, as evidenced by Yoshida et al. (2006), of record, Midland (2026) and Raja et al. (2008), as applied to Claims 19, 22, 23, 28, 30, 33-36, 43, 44, 48 and 51 above, and further in view of Cox et al. (1976).
The teachings of Yoshida et al. (2008) were discussed above.
Yoshida et al. (2008) did not teach a method wherein the transferring of the anaerobic RBC to the anerobic container is performed under positive pressure, as required by Claim 49.
Cox et al. teaches a chamber wherein an anaerobic jar can be opened and closed under anaerobic conditions and wherein a positive pressure in the chamber prevents oxygen contamination during connection and removal of the anaerobic jar (Pg. 41, Figs. 1-2 and Pg. 42, Column 1, 3rd paragraph and Column 2, 1st paragraph).
It would have been obvious to those of ordinary skill in the art before the instant invention to modify the method of Yoshida et al. (2008) of preparing stored anaerobic RBC wherein the composition is stored in an anaerobic jar to perform the transfer of the anaerobic RBC to the anaerobic container under positive pressure as taught by Cox et al. because this would maintain the anaerobic state of the stored anaerobic RBC. Those of ordinary skill in the art would have been motivated to make this modification because this would prevent contact by the stored anaerobic RBC with oxygen and/or carbon dioxide. There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, the anaerobic storage of oxygen and carbon dioxide susceptible materials.
Claims 19, 22, 23, 28, 30, 33-36, 43, 44, 45, 46, 48, 50 and 51 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Yoshida et al. (2008), of record, as evidenced by Yoshida et al. (2006), of record, Midland (2026) and Raja et al. (2008), as applied to Claims 19, 22, 23, 28, 30, 33-36, 43, 44, 48 and 51 above, and further in view of Dottori (US 6,403,124 B1).
The teachings of Yoshida et al. (2008) were discussed above.
Yoshida et al. (2008) did not teach a method further comprising irradiating stored anaerobic RBC in the anaerobic container with gamma or X-rays, as required by Claim 50.
Dottori teaches the sterilization of blood products contaminated with microbiological agents and improving reliability with respect to contamination is to irradiate the blood product with gamma irradiation after it is sealed in a container (Pg. 2, Lines 23-30).
It would have been further obvious to those of ordinary skill in the art before the filing date of the instant invention to modify the method of Yoshida et al. (2008) of preparing stored anaerobic RBC wherein the composition is stored in an anaerobic jar to further irradiate the stored anaerobic RBC with gamma rays as taught by Dottori
because this would eliminate any microbiological contamination of the stored anaerobic RBC. Those of ordinary skill in the art would have been motivated to make this modification in order to establish and/or maintain sterility of the stored anaerobic RBC
There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, the storage of blood products.
Response to Arguments
Applicant’s arguments, see Remarks, filed 12/08/2025, with respect to the rejection(s) of claim(s) 19, 22-23, 28, 30, 33-36, 38, 41 and 43-47 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Yoshida et al. (2008), as set forth above.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 04/22/2026
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