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 .
Election/Restrictions
Applicant’s election of Group I and Species A, corresponding to claims 1-5 and 7-22, in the reply filed on 07/06/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 6 and 23-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/06/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/07/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1-2, 16, and 19 are objected to because of the following informalities:
In claim 1, it is believed that a comma should be added after “neutrophils” in line 2.
In claim 1, it is believed line 17 should read “the second container containing” or similar.
In claim 2, it is believed the last line should read “the second container” rather than “such second container”.
In claim 16, change “the separation medium” to “the density separation medium” for consistency with the prior claims.
In claim 19 it is believed “pH” should read “the pH”.
In claim 19, it is believed “the concentration of sodium citrate to 0.1M” should read “the concentration of sodium citrate is 0.1M”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5 and 7-22 are 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 recites a composition that is “substantially free of neutrophils”. The term “substantially” is an approximation and the use of this term renders the claim indefinite because the specification does not contain any guideline that would apprise the skilled artisan of the metes and bounds of the claim (MPEP 2173.05). The specification appears to merely restate the claim language and does not provide any guideline as to which compositions would and would not be considered “substantially free of neutrophils”.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitation of a specific gravity between 1.065 to about 1.085 g/cm3, and the claim also recites “preferably a specific gravity of about 1.070 to about 1.080 g/cm3, and an optimal specific gravity of 1.077 g/cm3” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 17 recites the broad recitation of a pH is from about 6.5 to about 7.5, and the claim also recites “preferably 6.85 to about 7.15, and an optimal pH of 7.0” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 18 recites the broad recitation of wherein the concentration of sodium citrate anticoagulant is from about 0.05M to about 0.20M, and the claim also recites “with a preferred concentration of sodium citrate from about 0.08M to about 0.13M, with an optimal sodium citrate concentration range from about 0.09M to about 0.11M” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 18 recites the limitation "the concentration of sodium citrate anticoagulant" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 19 recites the limitation "the concentration of sodium citrate " in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the broad recitation of clot activation solution at a concentration of between 0.05M to 0.3M, and the claim also recites “clot activation solution at a concentration of between 0.05M to 0.3M, preferably between 0.1M to approximately 0.25M, with an optimal concentration of 0.2M” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In claim 22, it is unclear if the CaCl2∙2H2O limitation is required as it is in parentheses.
Dependent claims are rejected for the same reason(s) as the base claim(s) upon which they depend.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-5, 7-9, and 13-21 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al. (US Patent 5,667,963) in view of Turzi et al. (US Patent Application Publication 2018/0110917) (already of record).
Regarding claim 1, Smith et al. discloses a system for preparing a purified non-naturally occurring composition comprising monocytes and lymphocytes, and substantially free of neutrophils (the composition is free of granulocytes as they “are pelleted toward the bottom of the tube while the lymphocytes and monocytes form a highly purified mononuclear cell layer immediately above the thixotropic gel layer”; neutrophils are a granulocyte) (Abstract, col. 9 line 28-col. 10 line 30), the system comprising:
a first container (container or tube 12 in Figure; called separation tube in the Example) (col. 8 lines 24-28, col. 10 lines 39-55) having a sealable open end for receipt of a blood sample (col. 9 lines 38-46), and a closed end opposite the open end (col. 8 lines 17-28) (Figure);
the first container containing a density separation medium (16) disposed at a first position proximate the closed end (col. 8 lines 53-65) (Figure), and a thixotropic gel (14) having a density of about 1.055 to about 1.080 or about 1.075 to about 1.085 g/cm3 (falls within the claim range) disposed at a second position between the open end and the first position (col. 8 lines 17-65) (Figure), and an anticoagulant solution (18) having a pH of 7.0 (falls within the claim range) at a third position between the open end and the second position (col. 8 line 66-col. 9 line 15) (Figure),
wherein the first container is useable to produce an extractable suspension of separated monocytes and lymphocytes, and plasma, from the blood sample when centrifuged (col. 9 line 28-col. 11 line 14); and
a second container (called polystyrene round-bottom tube) having a sealable open end for receipt of an extracted suspension of separated monocytes, lymphocytes, and plasma produced in the first container (col. 10 line 38-col. 11 line 14).
As to the limitations regarding platelets, although Smith et al. does not explicitly disclose wherein the first container is useable to produce an extractable suspension of separated platelets along with the disclosed monocytes, lymphocytes and plasma, this limitation is necessarily present in the invention disclosed by Smith et al. as will be explained below.
Firstly, Smith et al. explicitly discloses that the first container is useable for “separating lymphocytes and monocytes from heavier phases of a sample of whole blood” (col. 10 lines 5-8); in use the lymphocytes, monocytes, and plasma rise above the gel which serves as a barrier while granulocytes are pelleted toward the bottom of the tube (col. 9 line 28-col. 11 line 14). Platelets are much smaller than other blood cells, such as lymphocytes and monocytes, and remain at the top of the container, within the plasma, during centrifugation, as is well known in the field of blood cell separation (see pp. 58-59 and 69-70 of “Cell Separation” which is cited herein as an evidentiary reference). Therefore, the first container disclosed by Smith et al. necessarily functions to produce an extractable suspension of separated platelets, monocytes, lymphocytes, and plasma from the blood sample when centrifuged, even if Smith et al. may not explicitly disclose the presence of the platelets.
Secondly, it is well established that when the structure recited in the reference is substantially identical to that of the claims, claimed properties of functions are presumed to be inherent (MPEP 2112.01). In this case, the prior art structure is identical to that of the claims, as discussed above (additionally, compare col. 9 lines 3-65 of the reference to para. 88-91 of the specification as-filed of the instant application; the reagents appear to be identical). Therefore, the claimed function of useable to produce an extractable suspension of separated platelets, monocytes, lymphocytes, and plasma from the blood sample when centrifuged is presumed to be inherent, and the burden shifts to the applicant to show otherwise.
As to the limitations regarding the wound-healing composition, this limitation does not introduce a patentable distinction over the prior art as it is directed to an intended use of a product the system is intended to produce, and does not impose a further structural limitation on the system. In any case, the system disclosed by Smith et al. is useable to produce a composition comprising monocytes and lymphocytes, as discussed above, and these cells have inherent wound-healing capabilities, consistent with Applicant’s specification (see para. 9 of the specification as-filed). Smith et al. further discloses wherein this composition is transferred into the second container which is a tube capable of being centrifuged (col. 10 lines 39-66). Therefore, Smith et al. fulfills the limitation of wherein the second container is useable to produce the wound-healing composition when centrifuged.
Smith et al. is silent as to wherein the second container contains a coagulation-activator.
Turzi et al. discloses a system for preparing a composition derived from a blood sample (para. 17-18) comprising a first container useable to produce a suspension of separated platelets, monocytes, lymphocytes, and plasma from the blood sample when centrifuged (para. 17-18, 355-358) and a second container for receipt of the suspension from the first container (para. 17-19, 70-74) (Fig. 3, sheet 2 of 12). Activating coagulation of the suspension results in a composition that is ready to be applied to a human for wound healing purposes (para. 236); thus, the system can be used to promote the healing of wounds to decrease infection risks, improve a patient’s recovery and comfort, and reduce medical care costs (para. 434).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the second container disclosed by Smith et al. to contain a coagulation-activator, as Turzi et al. discloses that it was known in the art to provide such a second container for the purpose of rendering a suspension of separated platelets, monocytes, lymphocytes, and plasma from a blood sample into a composition ready for application to a human, e.g. to use the composition for wound healing to obtain the numerous benefits thereof, and the skilled artisan would have been motivated to enhance the clinical utility of the system by enabling it to produce a composition ready for use with a human subject.
Regarding claim 3, Smith et al. discloses wherein the density separation medium comprises Ficoll-Paque (col. 8 lines 53-65), which is a Newtonian liquid (see col. 6 lines 8-19 of US Patent 4,957,638, which is cited herein as an evidentiary reference).
Regarding claim 4, Smith et al. discloses wherein the density separation medium comprises sodium diatrizoate (the density separation medium comprises Ficoll-Paque, see col. 8 lines 53-65, and Ficoll-Paque is composed of sodium diatrizoate, see p. 71 of “Cell Separation” which is cited herein as an evidentiary reference), which is an ionic substance having a molecular weight of less than about 1500, consistent with Applicant’s specification (see para. 71 of the specification as-filed).
Regarding claim 5, Smith et al. discloses wherein the density separation medium is sodium diatrizoate, as set forth above.
Regarding claim 7, Smith et al. discloses a first closure device for sealing the open end of the first container (col. 9 lines 38-46).
Regarding claim 8, Smith et al. discloses wherein the first closure device is adapted for vacuum sealing the open end of the first container (col. 9 lines 38-46).
Regarding claim 9, Smith et al. discloses wherein the first closure device is piercable by a cannula for supplying the blood sample to the first container by pressure differential (col. 9 lines 38-46).
Regarding claim 13, Smith et al. discloses wherein the purified wound-healing composition comprising platelets, monocytes, and lymphocytes is a mononuclear-platelet rich composition (the composition comprises monocytes and lymphocytes, which are mononuclear cells, separated from a blood sample, as discussed above, and therefore the composition necessarily comprises these components in a higher concentration than is found in baseline blood and reads on being “rich” in these components). As to the limitation of the composition being a fibrin matrix, this limitation does not introduce a patentable distinction over the prior art as it is directed to an intended product the system is intended to produce, and does not impose a further structural limitation on the system. In any case, Smith et al. in view of Turzi et al. discloses wherein the second container comprises a coagulation-activator, as set forth above, and Turzi et al. further discloses wherein the coagulation-activator activates the generation of fibrin (para. 33-34), and therefore, the second container taught by the prior art would be fully capable of being used to produce a fibrin matrix composition.
Regarding claim 14, Smith et al. discloses a centrifuge adapted to receive the first container (col. 10 lines 39-52).
Regarding claim 15, Smith et al. discloses wherein the thixotropic gel has a specific gravity of between 1.060 to about 1.065 g/cm3 (col. 8 lines 29-52).
Regarding claim 16, Smith et al. discloses the density separation medium, as set forth above.
Smith et al. is silent as to a specific gravity value of the density separation medium.
However, Smith et al. discloses general conditions for the specific gravity of mediums used for density separation of blood components (col. 8 lines 29-52) and further discloses that the density separation medium should have a specific gravity higher than that of the mononuclear cells but less than that of the other blood components (col. 1 lines 31-43).
It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions for the specific gravity of the density separation medium and one of ordinary skill in the art would recognize the parameter as a result-effective variable. Therefore, it would have been obvious to discover an optimum or workable range for the specific gravity of the separation medium by routine experimentation.
Regarding claim 17, Smith et al. discloses wherein the pH is 7.0, as set forth above.
Regarding claim 18, Smith et al. discloses wherein a concentration of sodium citrate anticoagulant is 0.1M (falls within the claim range) (col. 9 lines 16-22).
Regarding claim 19, Smith et al. discloses wherein the pH is 7.0, as set forth above, and further discloses wherein a concentration of sodium citrate is 0.1M (col. 9 lines 16-22).
Regarding claim 20, Smith et al. discloses wherein the anticoagulant comprises per liter 0.10 Molar 294 gm Sodium Citrate∙2H20, 0.27 gm Citric Acid-H20; and pH 7.0 (see LEUCOPREP citrate, col. 4).
Regarding claim 21, Smith et al. discloses wherein the anticoagulant comprises sodium citrate (col. 9 lines 7-22) rather than at least one of ethylenelendiaminetetraacetic acid disodium salt, ethylenelendiaminetetraacetic acid dipotassium salt or tripotassium salt as claimed.
However, Smith et al. discloses that it was known in the art to use either K3EDTA (ethylenediaminetetraacetic acid tripotassium salt) or sodium citrate as an anticoagulant (col. 3 lines 33-39).
It would have been obvious to one of ordinary skill in the art to substitute ethylenediaminetetraacetic acid tripotassium salt for sodium citrate as a matter of simple substitution of one known element for another to obtain predictable results (MPEP § 2143), in this case, substitution of one anticoagulant for another in order to obtain the predictable result of coagulating blood.
Claims 2, 10-12, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al. (US Patent 5,667,963) in view of Turzi et al. (US Patent Application Publication 2018/0110917) (already of record), as applied to claim 1, above, and in further view of Beretta et al. (US Patent Application Publication 2009/0258056) (already of record).
Regarding claim 2, Smith et al. discloses transferring the suspension of separated platelets, monocytes, lymphocytes, and plasma from the first container into the second container (col. 10 line 38-col. 11 line 14).
Smith et al. is silent as to the system comprising a transfer device adapted for coupling with the first container open end, and the second container open end, wherein the transfer device when coupled to the first container open end creates a sterile seal for receipt of the suspension of separated platelets, monocytes, lymphocytes, and plasma from the first container, and when coupled to the second container open end creates a sterile environment for transfer of the suspension of separated platelets, monocytes, lymphocytes, and plasma to such second container.
Beretta et al. discloses a system for preparing a composition derived from a blood sample (para. 20) comprising a first container (10) useable to produce a suspension of separated platelets and plasma from the blood sample (para. 129-130), a second container (14) useable to receive the suspension (para. 134), and a transfer device (18) useable to transfer the suspension from the first container to the second container (para. 134, 136). Specifically, the transfer device is adapted for coupling with an open end of the first container such that when coupled the transfer device creates a sterile seal for receipt of the system, and adapted for coupling with an open end of the second container such that when coupled the transfer device creates a sterile environment for transfer of the suspension to the second container (para. 127, 134-140).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the system disclosed by Smith et al. to comprise a transfer device as claimed, as Beretta et al. discloses that it was known in the art to use such a transfer device to transfer a separated fraction of a blood sample from one container to another in a sterile manner, and the skilled artisan would have been motivated to use a transfer mechanism recognized in the art to be suitable for transferring blood components without contamination.
Regarding claim 10, Smith et al. discloses transferring the suspension from the first container into the second container comprising an open end (col. 10 line 38-col. 11 line 14).
Smith et al. is silent as to a second closure device for sealing the open end of the second container.
Beretta et al. discloses a system for preparing a composition derived from a blood sample (para. 20) comprising a first container (10) useable to produce a suspension of separated platelets and plasma from the blood sample (para. 129-130), a second container (14) useable to receive the suspension (para. 134), and a transfer device (18) useable to transfer the suspension from the first container to the second container (para. 134, 136). Specifically, the second container comprises a closure device for vacuum sealing an open end thereof (para. 134), wherein the closure device is pierceable by a cannula of the transfer device such that the suspension can be transferred from the first container into the second container via the transfer device using a pressure differential, thereby allowing transfer in a sterile manner (para. 134-140).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the second container disclosed by Smith et al. to comprise a second closure device adapted for vacuum sealing the open end of the second container, wherein the second closure device is pierceable by a cannula for supplying the suspension by pressure differential, as Beretta et al. discloses that it was known in the art to use such a closure to transfer a separated fraction of a blood sample from one container to another in a sterile manner, and the skilled artisan would have been motivated to use a closure device recognized in the art to be suitable for transferring blood components without contamination.
Regarding claim 11, Smith et al. as modified by Beretta et al. teaches wherein the second closure device is adapted for vacuum sealing the open end of the container, as set forth above.
Regarding claim 12, Smith et al. as modified by Beretta et al. teaches wherein the second closure device is pierceable by a cannula for supplying the suspension of separated platelets, monocytes, lymphocytes, and plasma to the second container by pressure differential, as set forth above.
Regarding claim 22, Smith et al. in view of Turzi et al. teaches the coagulation-activator, as set forth above. Specifically, Turzi et al. discloses wherein the coagulation-activator is a calcium chloride clot activation solution (para. 34, 372) and wherein the calcium content should be about 0.463 mmol per 2 mL (para. 372), which is equivalent to about 0.2M. Therefore, the prior art combination arrives at wherein the coagulation-activator is a calcium chloride clot activation solution at a concentration of 0.2M.
The prior art combination is silent as to wherein the coagulation-activator is a calcium chloride (CaC12∙2H2O) clot activation solution.
Beretta et al. discloses a system for preparing a composition derived from a blood sample (para. 20) comprising a first container (10) useable to produce a suspension of separated platelets and plasma from the blood sample (para. 129-130) and a second container (14) useable to receive the suspension (para. 134), the second container comprising a coagulation activator for coagulating the suspension upon receipt in the second container (para. 134). Specifically, Beretta et al. discloses wherein the coagulation activator is a calcium chloride clot activation solution, prepared from CaC12∙2H2O, wherein receiving the suspension into a second container comprising such a coagulation activator allows the suspension to be coagulating such that it is “ready to be immediately used” (para. 239-241).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the coagulation-activator taught by Smith et al. in view of Turzi et al. to be prepared from CaC12∙2H2O, based on the teachings of Beretta et al., as the skilled artisan would have been motivated to use a coagulation-activator recognized in the art to be useful for preparing a composition immediately ready for use.
.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Wang (US Patent Application Publication 2019/0366328) is directed to a container comprising a density gradient medium disposed at a lower closed end, a gel barrier above the density gradient medium, and an anticoagulant coating disposed on an inner wall of the container above the gel barrier.
Conclusion
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799
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