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 claims
Claims 1, 2, 4, 7, 9-12, 14-17, 19-21, 23 and 25-28 as amended on 7/14/2025 are pending.
Claims 9-12, 14-17, 19-21, 23 and 25-28 were withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 1, 2, 4, and 7 as amended on 7/14/20205 are under examination in the instant office action.
Claim Rejections - 35 USC § 112
Indefinite
Claims 1, 2, 4, and 7 as amended rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 as amended is rendered indefinite by the phrase “at concentrations less than 12%” because it is unclear whether this phrase refers to total amount or to amount of each or to amount of HES.
New matter
Claims 1, 2, 4, and 7 as amended are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Insertion of the limitation that is a phrase “at concentrations less than 12%” has no support in the as-filed specification. The insertion of this limitation is a new concept because it neither has literal support in the as-filed specification by way of generic disclosure, nor are there specific examples of the newly inserted limitation that would show possession of the concept of the use of the claim-recited amount.
First, there no generic disclosure about concentrations such as “less than 12%”.
The exemplified disclosure (par. 0038 of published application US 2022/0378840) describes the use of 2-3% concentrates of each of three cryoprotectants (carnitine, HES and albumin) in a bag with a “specified” volume of RBS, wherein the “specified” volume of RBS is not specified.
This is not a sufficient support for the newly inserted phrase. This is a matter of written description, not a question of what one of skill in the art would or would not have known. The material within the four corners of the as-filed specification must lead to the generic concept. If it does not, the material is new matter. Declarations and new references cannot demonstrate the possession of a concept after the fact. Thus, the insertion of the phrase “at concentrations less than 12%” is considered to be the insertion of new matter for the above reasons.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4 and 7 as amended are/remain rejected under 35 U.S.C. 103 as being unpatentable over Greenwood et al (“Hydroxyethyl Starch as a Cryoprotective Agent for Human Red Blood Cells”. Die Starke, 1977. No. 10, pages 343-347), Sputtek et al (IDS reference; Transfusion Medicine and Hemotherapy, 2007, 34, 262-263) and Arduini et al (IDS reference; Transfusion 1977, Vol. 37, pages 166-174).
The cited reference by Greenwood teaches cryopreservation of red blood cells (RBCs) with a cryoprotective agent HES in the presence of plasma proteins or albumin (entire document including page 343, col. 2).
Thus, the cited reference discloses a kit or a system for low temperature storage of packed RBCs comprising: i) a freeze-resistant container or a can comprising HES, plasma proteins (albumin) and packed RBCs; ii) generic packaging or holder for cans; and iii) generic description of procedure protocol or instructions.
The cited reference by Greenwood clearly recognizes HES as an effective cryoprotectant (abstract). The cited reference by Greenwood clearly recognizes that plasma proteins provide for stabilization of red cell membrane (page 346, col. 2, line 14), thereby, for edema reduction. The cited reference by Greenwood clearly recognizes albumin as an essential or main protein of plasma proteins (page 346, col.2, par. 1). Although Greenwood is silent about MW of HES, the prior art, for example: Sputtek, teaches the optimal characteristics for HES as intended for cryopreservation of erythrocytes or RBC are MW about 200 kDa and DS (degree of hydroxyethylation of starch) about 0.5 or 50% (see page 264, col. 2, line 12 from the bottom) which fall within the claim-recited ranges. Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to select HES with optimal characteristics as taught as by Sputtek for the use in in the low temperature RBC storage system of Greenwood.
In particular and with regard to the HES amounts, the reference by Greenwood discloses the use of HES concentration at about 10% (page 344, col. 2, line 17). The reference by Greenwood also teaches that recovery of red blood cells after freezing is about the same at as low as 8% HES and at as high as 16% HES (page 345, col.1, lines 10-11). The cited reference also teaches that HES might be retained in the body after infusion of product with red blood cells (page 345, col.1, it. 3.2), thereby, suggests decreasing amount of HES. The cited reference by Greenwood also recognizes that the use of cryoprotectant agent must involve compromises between theoretically most advantageous choices and those which are practically expedient (page 346, last par.)
As a whole, the cited reference by Greenwood is silent about incorporation of carnitine.
However, the prior art teaches that addition of L-carnitine to RBCs stored at low temperature reduce hemolysis and improves viability of RBCs. For example: see Arduini entire document including abstract. In particular, Arduini discloses the use of carnitine in amount 5mM (see page 167, col. 2, par. 2) or 0.083% .
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to add L-carnitine to the low temperature storage system of Greenwood with a reasonable expectation of success in preserving RBCs because prior art teaches and suggests that addition of L-carnitine to RBCs stored at low temperature reduce hemolysis and improves viability of RBCs. It would be obvious for one skills the art to optimize concentrations of cryoprotectants depending on practical uses as recognized by Greenwood and to decrease amount cryoprotectants to avoid prolong retention of cryoprotectants after infusion of red blood cells that were priorly cryopreserved as suggested by Greenwood.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary. The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references.
Therefore, the claims 1 and 4 are properly rejected under 35 USC § 103.
With respect to claim 7 it is noted that both cited references teach preservation of RBC that are free from plasma white cells. The cited refences clearly teach preservation of red cell from blood, and, thus, the teaching about red cell preservation is reasonably expected to be suitable for red cell originating from umbilical cord blood.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary. The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references.
Therefore, the claims are properly rejected under 35 USC § 103.
Claims 1, 2, 4 and 7 as amended are/remain rejected under 35 U.S.C. 103 as being unpatentable over Greenwood et al (“Hydroxyethyl Starch as a Cryoprotective Agent for Human Red Blood Cells”. Die Starke, 1977. No. 10, pages 343-347), Sputtek et al (IDS reference; Transfusion Medicine and Hemotherapy, 2007, 34, 262-263) and Arduini et al (IDS reference; Transfusion 1977, Vol. 37, pages 166-174) as applied to claims 1, 4 and 7 above, and further in view of Baar (IDS reference; Transfusion 1973, Vol. 13, No. 2, pages 73-83).
The cited Greenwood, Sputtek and Arduini as above.
The cited reference by Greenwood teaches the use of plasma proteins in the composiotns for preservation for RBS and it clearly recognizes albumin as an essential or main protein of plasma proteins (page 346, col. 2, par. 1) suitable for preservation and stabilization of RBCs.
Further, as applied to claim 2, the cited reference by Baar explicitly teaches the use of albumin (or human serum albumin) in a combination with HES (entire document including title) for preservation and stabilization of blood cell samples (page 74, col. 2, lines 1-3) including RBCs. The reference by Baar discloses the use of albumin in amount 7% (page 75, col.1, lines 13-14). The refence by Baar also recognizes that reagents for preservation are commonly provided in freeze-dried forms (see section “materials and methods”).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to use albumin as a main plasma protein in the low temperature storage system of Greenwood with a reasonable expectation of success in preserving RBCs because prior art teaches and suggests that albumin provides preservation of red blood cells and stabilization of cellular membrane and shape, thereby, reducing RBC edema. One of skill in the art would clearly and obviously recognize that all reagents for preservation are commonly provided in freeze-dried forms.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed 7/14/2025 have been fully considered but they are not persuasive.
With regard to claim rejection under 35 USC § 103 Applicants main arguments are based on new limitation draw to ingredient concentrations less than 12%.
First, this argument is not found particularly persuasive because it is not clear whether the claim-recited phrase “less than 12%” refers to total amounts or amount of each or amount of HES.
The argument is not considered persuasive because the prior art, in particular the cited reference by Greenwood, teaches that cryoprotectants or HES might be retained in the body after infusion of product with red blood cells (page 345, col.1, it. 3.2), thereby, suggests decreasing amount of cryoprotectants including HES. The cited reference by Greenwood also recognizes that the use of cryoprotectant agent must involve compromises between theoretically most advantageous choices and those which are practically expedient (page 346, last par.). Thus, it would be obvious for one skills the art to optimize concentrations of cryoprotectants depending on practical uses of the final product and to decrease amount cryoprotectants to avoid prolong retention of cryoprotectants after infusion of red blood cells that were priorly cryopreserved as suggested by Greenwood.
No claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Vera Afremova
October 1, 2025
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653