DETAILED ACTION
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 .
Status of the Clams
Claims 35-46, 48-53, 89-91, and 93 are pending.
Claims 35-36, 41-46, 48-53, and 91 are newly amended.
Claim 93 is newly added.
Claims 35-46, 48-53, 89-91, and 93 are under examination on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 35-40, 53, and 89-91 under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited) is withdrawn to address the claimed as amended.
The rejection of claims 35, 41-46, and 48-52 under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited) and Sharma et al. (Asian J Tranf Sci, 2010, previously cited) is withdrawn to address the claimed as amended.
The rejection of claim 92 is rejected 35 U.S.C. 103 as being unpatentable over Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) in view of view of Masse (Transfus Clin Biol, 2001, previously cited), as evidenced Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited) is withdrawn to address the claimed as amended.
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.
Claims 35-46, 48-53, 89-91, and 93 are rejected under 35 U.S.C. 103 as being unpatentable over Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) in view of Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
In regards to claims 35-39, and 89-90, as newly amended, the claim is drawn to a “stored oxygen and carbon dioxide reduced leukoreduced whole blood composition for use in transfusion therapy of a trauma patient in need of multiple transfusion.”
While the claims are drawn to a product (a composition), storing that product is a process step. Thus, claim 35 is a product-by-process claim.
In regards to product-by-process claims, according to MPEP 2113, that while the structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979), and that the claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
It is further noted that the process steps include storing leukoreduced whole blood with platelets (hereafter referred to as “the stored blood”) under oxygen and carbon dioxide reduced conditions throughout the storage period wherein the oxygen saturation is 30% or less and wherein the partial pressure of carbon dioxide is less than 60 mmHg. As limited in claim 35, leukoreduction results in levels of white blood cells that are at least 5 logs compared to levels of white blood cells present in unprocessed whole blood. As a result of storage under these conditions, the stored blood has 2,3-DPG levels after 15 days that is greater than the 2,3-DPG levels at day zero.
Thus, the process steps impart distinctive structural characteristics to the final product.
Turning to the prior art, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide depletion maintains 2,3-DPG levels higher for three weeks compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to claim 40, Yoshida teaches embodiments wherein AS-3 (which comprises citrate-phosphate-dextrose and adenine) is added to is added to blood (paragraph [0031]).
In regards to claim 41, whether the OCR-LRWB has reduced levels of a biologic modifier (BRM) selected from the group consisting of a cytokine, a chemokine, an ispropstane, and an oxidized lipid product relative to non-OCR-LRWB, this is a property of OCR-LRWB not a limitation per se.
This is supported by the specification which states “oxygen reduced leukoreduced whole blood (OR-LRWB) . . . has reduced levels of biological response modifiers (BRMs) relative to conventionally stored whole blood (paragraph [0074]).
Additionally, as evidenced by Sharma, it is known in the art that the process of leukoreduction itself is sufficient reduce inflammatory cytokines (BRMs) accumulation during storage which reduces immune responses in patients (with a variety of conditions) following transfusion (Timing of Leukofiltration, p4).
Therefore, since Yoshida 2012 teaches the stored leukoreduced whole blood product of claim 35, the product as disclosed by Yoshida 2012, would have the same properties as in claims 41 absent evidence to the contrary.
In regards to claims 42-46 and 48, whether the leukoreduced whole blood product has reduced inflammatory response relative to a patient in need with a different blood product (as are any of the other conditions in claims 43-48, such as “reduced immune modulation”, as in claim 43), these are also properties of the if transfused in the patient and are intended uses.
In the instant case, as above, as evidenced by Sharma, it is known in the art that the process of leukoreduction itself is sufficient reduce inflammatory cytokines (BRMs) accumulation during storage which reduces immune responses in patients (with a variety of conditions) following transfusion (Timing of Leukofiltration, p4).
Therefore, since Yoshida 2012 discloses the stored leukoreduced whole blood product of claim 35, the product as disclosed by Yoshida 2012, would have the same properties as in claims 42-46 and 48 or would be expected to be suitable for these intended uses absent evidence to the contrary.
In regards to claims 49-52, in regards to whether the leukoreduced whole blood has equivalent or better coagulation parameters as measured by thromboelastography (or equivalent or better parameters or levels of conditions in claims 50-52), these are properties of stored leukoreduced whole blood, if measured, and do not require additional process steps. Thus, they have been interpreted as optional. Furthermore, since Yoshida 2012 discloses the stored leukoreduced whole blood product of claim 35, the product as disclosed by Yoshida 2012, would have the same properties as in claims 449-52 is further process steps were performed, absent evidence to the contrary.
In the instant case, as above, as evidenced by Sharma, it is known in the art that the process of leukoreduction itself is sufficient reduce platelet-refractoriness (p.5, col2, see Table 3), thereby allowed stored leukoreduced blood to exhibit equivalent or greater TEG coagulation parameters than stored non-leukoreduced blood.
In regards to claim 53, Yoshida teaches that the blood can be stored for at least three weeks (paragraph [0006]).
In regards to claim 91, these are intended uses of the preamble (see MPEP 2111.02). As discussed above, Yoshida 2012 teaches that the composition can be transfused to patients broadly (paragraph [0022]). Therefore, Yoshida 2012 is suitable for these intended uses absent evidence to the contrary.
In regards to claim 93, Yoshida 2012 teaches that the blood can be stored for at least 7 weeks (claim 5), which overlaps with the claimed range.
Therefore, the combined teachings of Yoshida 2012 and Masse renders the invention unpatentable as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 35-46, 48-53, 89-91, and 93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 17/772,947 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
Although the conflicting claims of copending Application No. 17/772,947 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets) and leukoreduced, wherein the blood is oxygen and carbon dioxide-reduced, at levels of less than 30% and 60 mm Hg, respectively.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 35-46, 48-53, 89-91, and 93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-41 of copending Application No. 18/152,140 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
Although the conflicting claims of copending Application No. 18/152,140 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets) and leukoreduced, wherein the blood is oxygen and carbon dioxide-reduced, at levels of less than 30% and 60 mm Hg, for use in trauma patients respectively.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 35-46, 48-53, 89-91, and 93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35, 49, 89-105 of copending Application No. 17/954,138 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
Although the conflicting claims of copending Application No. 17/954,138 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), wherein the blood is oxygen and carbon dioxide-reduced, at levels of less than 30% and 60 mm Hg, respectively.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 35-46, 48-53, 89-91, and 93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, 22-23, 28, 30, 33-36, 38, 41, 43-51 of copending Application No. 16/289,118 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
Although the conflicting claims of copending Application No. 16/289,118 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), wherein the blood is oxygen and carbon dioxide-reduced, at levels of less than 30% and 60 mm Hg, respectively, and with 2,3-DPG levels that are higher after storage.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 35-46, 48-53, 89-91, and 93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 109-116 and 121-128 of copending Application No. 18/297,193 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
Although the conflicting claims of copending Application No. 18/297,193 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets) , wherein the blood is oxygen-reduced, at levels of less than 30%.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,033,581 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 11,033,581 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), wherein the blood is oxygen-reduced, at levels of less than 30%.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,576,931 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 11,576,931 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for treating trauma patients wherein the blood is oxygen-reduced, at levels of less than 30% and carbon dioxide reduces at a level of 60 mmHg or less.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,583,192 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 10,583,192 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for treating trauma patients wherein the blood is oxygen-reduced, at levels of less than 30% and carbon dioxide reduces at a level of 60 mmHg or less and where 2,3-DPG levels that are higher after storage.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,147,876 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 11,147,876 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for administration to a trauma patient wherein the blood is oxygen-reduced, at levels of less than 30%.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,911,471 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 11,911,471 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for treating trauma patients wherein the blood is oxygen-reduced, at levels of less than 30% and carbon dioxide reduces at a level of 60 mmHg or less and where 2,3-DPG levels that are higher after storage.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,364,760 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 12,364,760 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for treating trauma patients wherein the blood is oxygen-reduced, at levels of less than 30% and carbon dioxide reduces at a level of 60 mmHg or less and where 2,3-DPG levels that are higher after storage.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,013,771 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 11,013,771 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for administration to a trauma patient wherein the blood is oxygen-reduced, at levels of less than 30%.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,339,025 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 9,339,025 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for administration to a trauma patient wherein the blood is oxygen-reduced, at levels of less than 30% (as evidenced by Severinghaus, 10 mmHg O2 is an oxygen saturation of 9.58%) and wherein carbon dioxide is reduced to less than 60 mm Hg.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Claims 35-46, 48-53, 89-91, and 93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,251,387 B2 in view of Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) and Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously
Although the conflicting claims of copending U.S. Patent No. 10,251,387 are not identical to the currently prosecuted claims, they are not patently distinct from each other because said claims of both inventions are drawn to stored oxygen-reduced blood that can be whole blood (which comprises platelets), for administration to a trauma patient wherein the blood is oxygen-reduced, at levels of less than 30% (as evidenced by Severinghaus, 10 mmHg O2 is an oxygen saturation of 9.58%) and wherein carbon dioxide is reduced to less than 60 mm Hg.
In regards to the process steps and their effects on the stored blood, these were all known in the art before the effective filing date.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide results in higher 2,3-DPG following three weeks of storage compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to the embodiments of claims 36-46, 48-53, 89-91, and 93, these embodiments were all known in the art or are properties of stored, as taught by Yoshida 2012 as discussed in depth above (see discussion under 35 USC 103). A person of ordinary skill in the art would have been motivated to include these because, as above, Yoshida 2012 teaches that the stored blood can be used for transfusion patients. Furthermore, because they are known embodiments for stored blood and because Yoshida 2012 is the same inventor, it could have been done with predictable results and a reasonable expectation of success.
Response to Arguments
Applicant argues that the claims as amended overcome the rejections under 35 USC 102 (Remarks, p9-15).
Applicant’s arguments filed 05/08/2026 have been fully considered and are persuasive. Therefore, the rejections under 35 USC 102 have been withdrawn. However, the claims as amended are still prima facie obvious over Yoshida et al. (US20120225416A1, on IDS 04/27/2021, hereafter “Yoshida 2012”, previously cited) in view of Masse (Transfus Clin Biol, 2001, previously cited) as evidenced by Severinghaus (Journal of Applied Physiology, 46(3): 599-602, 1979, previously cited), Sharma et al. (Asian J Tranf Sci, 2010, previously cited), and Duhn et al. (Pflügers Archiv, 1971).
Applicant argues that when read as a whole, Yoshida 2012 supports maintenance of 2,3-DPG levels in O2 and CO2-depleted RBCs only (Remarks, p11-12). Applicant also argues that Yoshida 2012’s experimental data refers to RBCs alone (Remarks, p12). Relatedly, Applicant argus that Example 2 of Yoshida 2012 details packed RBCs (Remarks, p12-13). Continuing, Applicant argues that claim 35 requires that 2,3-DPG levels that are greater in OCR-LRWB+PLT blood not RBCs in acidified additive solution (Remarks, p12). Applicant argues that it has not been established that the claimed elements are inherently established (Remarks, p14-15).
Applicant’s arguments filed 05/08/2026 have been fully considered but are not found persuasive.
As discussed above, Yoshida 2012 teaches a stored “red blood cell sample” (paragraph [0005]; claims 1 and 14). Yoshida 2012 teaches that this sample can be whole blood specifically (paragraph [0006]; claim 14). Furthermore, because Yoshida 2012 teaches that the blood is whole blood, and does not indicate that platelets were removed, a person of ordinary skill in the art would have recognized that the whole blood of Yoshida 2012 contains platelets.
Yoshida 2012 teaches that the blood is suitable for transfusion to patients over multiple weeks (paragraph [0022]), and is therefore, at least capable of performing the intended use of the stored blood composition for therapy of a trauma patient in need of multiple transfusions (see MPEP 2111.02 for the effect of the preamble and intended uses).
Continuing, Yoshida 2012 teaches that the sample can be treated to remove leukocytes (paragraph [0011]).
While Yoshida 2012 is silent as to the level of leukoreduction, a person of ordinary skill in the art would have been motivated to reduce white blood cells by at least 5 logs in order to reduce the chances of triggering an immune response in transfusion recipients. For example, as taught by Masse, 5 log depletion of leukocytes results in elimination of 99.90% of leukocytes and provides better blood transfusion safety (Summary, p297; Leukocyte technology, p298). Furthermore, because Masse teaches that, methods for reducing leukocytes by 5 logs is known in the art (Leukocyte technology, p298), it could have been done with predictable results and a reasonable expectation of success.
Continuing, in addition to leukoreduction, Yoshida 2012 teaches that blood samples can be depleted of both oxygen and carbon dioxide and stored in an oxygen and carbon dioxide impermeable environment for at least three weeks, which overlaps with the claimed storage range (claim 1; paragraph [0006]).
In regards to the levels of the oxygen and carbon dioxide reduced conditions, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
Additionally, Yoshida 2012 teaches that blood samples are depleted of oxygen and carbon dioxide, transferred to an oxygen and carbon dioxide impermeable environment for storage (paragraph [0006]), and that it is required that CO2 is removed from anaerobic (thus, oxygen-depleted conditions) before and during storage of RBCs (paragraph [0010]). Thus, a person of ordinary skill in the art would have recognized that the oxygen and carbon dioxide depleted conditions are continuous (and are also the pre-storage levels as in claims 89-90).
In regards to the oxygen and carbon dioxide depletion levels, Yoshida teaches that the partial pressure of O2 and CO2 can be reduced to about 10 mmHg and 5 mmHg, respectively (paragraph [0015]).
A partial pressure of 5 mmHg CO2 overlaps with the range of less than 60 mmHg as in claim 1 (or between 1 and 60 mmHg as in claim 39; or between 1 and 20 mmHg as in claim 90).
In regards to the oxygen levels, as evidenced by Severinghaus, oxygen at a partial pressure of 10 mmHg (mmHg = 1 Torr) is percent saturation of about 9.58%, which is less than 30% as in claim 1 (or 20% as in claim 38; or 10% as in claim 90).
In regards to the greater 2,3-DPG levels over 15 days, this is a natural effect of storing the whole blood under the oxygen and carbon dioxide reduced conditions for 15 days. In the instant case, because Yoshida 2012 teaches the same conditions over the same amount of time, the stored composition of Yoshida 2012 would have the same property of greater 2,3-DPG levels over 15 days, absent evidence to the contrary. Indeed, Yoshida 2012 teaches that oxygen and carbon dioxide depletion maintains 2,3-DPG levels higher for three weeks compared to samples in which either oxygen nor carbon dioxide were depleted (paragraphs [0021, 0033]; claim 18). Specifically, Yoshida 2012 teaches that “Oxygen depletion has a positive impact on ATP levels in red blood cell samples and carbon dioxide depletion has a positive impact on 2.3-DGP levels. Optimal results are achieved when both oxygen and carbon dioxide are depleted” (paragraph [0033]).
Moreover, as above, as taught by Yoshida 2012, 2,3-DAG is glycolic intermediate produced in the cytosol of RBCs themselves (see paragraph [0008]; Scheme 1).
This is confirmed by Duhm, who evidences that deoxygenation results in upregulation of the synthesis of 2,3-DPG in mammalian (at least human and rat) RBCs both in vitro and in vivo (Summary, p254; Fig. 8, p264; Fig. 9, p266; Discussion, p264). Thus, it is long known that increased 2,3-DPG levels are a natural phenomenon of exposing RBCs to hypoxic conditions (see specifically, Fig. 8, p254 of Duhm).
Thus, increases in 2,3-DPG levels in oxygen and carbon dioxide depleted conditions are the result of production by RBCs per se, and a whole blood sample – which would include RBCs – would have this same effect.
Therefore, the stored composition of Yoshida 2012 in fact has the same effect.
In regards to Applicant’s arguments that Yoshida 2012 as a whole refers to RBCs alone, as discussed in the Response to Arguments on 11/10/2025 (see pages 30-31),
In regards to red blood cells, the stored blood composition of Yoshida 2012 is specifically a “red blood cell sample” (paragraph [0005]; claim 1), which can explicitly be whole blood specifically (paragraph [0006]; claim 14). Indeed, Yoshida 2012 explicitly states “the red blood cell sample is . . . whole blood” (claim 14). See also paragraph [0011], “For the purposes of this invention, a red blood cell sample refers to whole blood.”
Thus, not only can the red blood sample explicitly be whole blood, but therefore, also, the effects depleting oxygen and carbon dioxide which “maintains 2,3-DPG levels higher for three weeks than 2,3-DPG levels in a red blood cell sample in which neither oxygen nor carbon dioxide are depleted” (as in claim 18) is a property of stored whole blood as taught by Yoshida 2012.
In regards to the double-patenting rejections, Applicant argues that none of the cited co-pending applications or patents recite the claimed features (Remarks, p16-37).
Applicant’s arguments filed 05/08/2026 have been fully considered but are not found persuasive.
It would have been prima facie obvious to modify the compositions of the co-pending applications or patents to arrive at the instantly claimed invention as discussed in depth above.
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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