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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/21/2025 has been entered.
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 11/21/2025 are acknowledged. Claim 1 is amended; claims 8-9, 11, 14-24 and 27 are canceled; no claims are withdrawn; claim 35 is new; claims 1-7, 10, 12-13, 25-26 and 28-35 are pending and have been examined on the merits.
Claim Rejections - 35 USC § 112
The rejection of claims 1-7, 10, 12-13 and 25-34 under 35 U.S.C. § 112(a), as set forth at pp. 4-7 of the previous Office Action is moot regarding claim 27 due to cancelation of the claim and is withdrawn regarding the remaining claims in view of the amendment of the claims.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 35 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim 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.
New claim 35 constitutes new matter because the original disclosure does not disclose that the transferring one or more portions of the plasma comprises: “as the separator tube is coupled to the separator tube port, the air needle extends further toward a cap of the separator tube than the plasma needle to enable the air needle to penetrate the cap before the plasma needle is able to penetrate the cap to enable the interior of the separator tube to become coupled to the external air before becoming coupled to the syringe port, thereby enabling an equalization of air pressure within the interior of the separator tube with air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port”; hence, claim 35 constitutes new matter and is rejected under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter.
Response to Arguments
Applicant's arguments filed 11/21/2025 have been fully considered but they are not persuasive.
Regarding the rejection under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter, Applicant alleges (Remarks received 11/21/2025, pp. 12-15) that the portion of claim 35 identified as new matter above is not new matter. Applicant argues that drawings can provide written description; however, none of the instant drawings provide written description for the method steps identified as new matter above. As discussed in the previous Office action and documented below, the original specification discloses the simultaneous equalization of pressures between the separator tube, transfer syringe and external air (see below) NOT a method step comprising inserting only the longer air needle into the interior of the separation tube, letting the pressure between the separator tube and the external air equilibrate followed by a pressure equalization with the transfer syringe when the shorter plasma needle is inserted; hence, claim 35 is rejected for constituting matter above.
Practitioner’s arguments on pp. 15-17 attempting to support this 3-step method from the original disclosure is completely unpersuasive. The original disclosure, relevant portions quoted below, speaks for itself and clearly does not support this 3-step method.
The original disclosure discloses that the pressure between the separator tube interior, the external air and the transfer syringe is equalized simultaneously, rather than the 3-step procedure of claim 35:
[0049] of the original specification discloses “As is about to be described, each of the different types of transfer device 1300a, 1300b and 1300c is configured to enable plasma 13 to be transferred from a separator tube 1200a or 1200b coupled to the separator tube port 1320, and to a transfer syringe 1400 coupled to the syringe port 1340. Additionally, and as is also about to be described, each of the different types of transfer device 1300b and 1300c is additionally configured to also enable external air surrounding the transfer device 1300b or 1300c to be drawn in through an air filter 1350 at the filtered air port 1330, and conveyed to the separator tube 1200a or 1200b that coupled to the separator tube port 1320” (emphasis added); thus, external air is equilibrated with the interior of the separator tube when the tube is coupled to the separator tube port, not before.
[0053] of the original specification discloses “FIG. 2E depicts aspects of the manner in which the dual-flow device 1300b enables a simultaneous transfer of filtered air 93 into a separator container 1200a or 1200b, and of plasma 13 out of the separator container 1200a or 1200b as part of transferring plasma 13 to the transfer syringe 1400. As depicted, the separator tube port 1320 may incorporate both an air needle 1329 and a plasma needle 1321 that are each positioned to penetrate through the cap 1210 of a separator tube 1200a or 1200b to enable the flow through each of gases and/or liquids into and/or out of such a separator tube 1200a or 1200b. Again, the syringe port 1340 may be configured to form a connection with an end connector 1410 carried at one end of the transfer syringe 1400.” (emphasis added); thus, the transfer of external air into the separator tube and withdrawal of plasma from the separator tube is simultaneous, NOT that the air goes in before the plasma is withdrawn.
[0054] of the original specification discloses “As depicted, with a separator tube 1200a or 1200b coupled to the separator tube port 1320 such that the needles 1321 and 1329 penetrate the cap 1210 thereof, and with the end connector 1410 of the transfer syringe 1400 coupled to the syringe port 1340, there may be an initial equalization of pressures thereamong. More specifically, and especially where a vacuum separator tube 1200b is coupled to the separator tube port 1320, external air 99 may be drawn into the dual-flow device 1300a through the air filter 1350 of the filtered air port 1330, and then the resulting filtered air 93 may be conveyed into a separator tube 1200a or 1200b at the separator tube port 1320 via the air needle 1329. Pulling the plunger 1440 of the transfer syringe 1400 in a direction away from the end connector 1410 thereof may then draw plasma 13 from within the separator tube 1200a or 1200b, and into the transfer syringe 1440, via the plasma needle 1321 and the end connector 1410. In turn, more filtered air 93 may be drawn into the separator tube 1200a or 1200b to replace the plasma 13 that is so drawn out.” (emphasis added); thus, equalization of pressures happens when both needles are penetrating the separator tube NOT equalized before the separator tube is coupled to the separator tube port as stated in claim 35 - “as the separator tube is coupled to the separator tube port, the air needle extends further toward a cap of the separator tube than the plasma needle to enable the air needle to penetrate the cap before the plasma needle is able to penetrate the cap to enable the interior of the separator tube to become coupled to the external air before becoming coupled to the syringe port, thereby enabling an equalization of air pressure within the interior of the separator tube with air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port”.
Hence, claim 35 clearly constitutes new matter which must be removed from the claim to overcome this rejection.
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 1-7, 10, 12-13 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron, US 2023/0172989 (cite A, PTO-892, 6/13/2024; herein “Esteron”) in view of Hanna et al., US 2015/0174221 (cite B, PTO-892, 6/13/2024; herein “Hanna”), Mijers et al., US2020/0146939 (cite A, PTO-892, 4/15/2025; herein “Mijers”) and Sealfon et al., US 2018/0116909 (cite A, PTO-892, 8/8/2025; herein “Sealfon”).
Esteron teaches methods for treating a respiratory condition or disorder of a subject ([0071-72]; [0073]; p. 6, claim 11) with a composition enriched in alpha-2-macroglobulin (α2M herein; [0009], [0041], [0043], [0073]) wherein the method comprises drawing whole blood ([0050], [0052-54]), separating plasma containing α2M molecules from other components of the whole blood with a separator tube comprising a separator gel ([0007-10], [0031], [0033], [0035-38], [0073]; p. 6, claim 1), isolating the α2M molecules from other components of the plasma which can be with a filter ([0012], [0046-49], [0073]; pp. 6-7, claims 8 and 28), and administering the composition enriched in α2M molecules to the patient via inhalation with a nebulizer ([0013], [0071-72]; p. 6, claim 11).
Esteron teaches that the blood can be autologous to the patient [0055], i.e., wherein the whole blood is drawn from the patient in support of treating the patient with the α2M molecules in an autologous manner.
Esteron teaches that separating the plasma from other components of the whole blood comprises: depositing the whole blood into a separator tube which contains an amount of separator gel; and subjecting the separator tube to a centrifugal force for a first predetermined period of time to cause a combination of the first centrifugal force and the separator gel within the separator tube to separate the plasma of the whole blood within the separator tube from red blood cells and white blood cells of the whole blood within the separator tube ([0007-10], [0031-33], [0035-38], [0073], [0074]; p. 6, claim 1).
Esteron teaches removing the α2M-enriched plasma (26 in Fig. 4) from above the separator gel (24 in Fig. 4) with a syringe attached to a transfer device comprising a hollow needle by piercing the septum of the separator tube and withdrawing the plasma (denoted by the arrow in Fig. 4; [0033], [0052]). The plasma can then be inserted into the next tube in the process by pressing on the plunger of the syringe and expelling the plasma (e.g., as in Fig. 5). Esteron teaches that the α2M-enriched plasma (third cellular fraction in Esteron) can be further concentrated by centrifugation [0033] or filtration with a hemoconcentrator comprising a 15 kDa filter which removes water and low molecular weight components and specifically recites that this enriches the composition for α2M [0073], but Esteron does not specifically teach isolating the α2M molecules from other components of the plasma by centrifuging the plasma containing the α2M molecules in a tube comprising a filter with a molecular weight cut off ranging from 100 kDa to 500 kDa; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice said method of further isolating the α2M molecules in view of the disclosure of Hanna.
Hanna teaches methods for isolating alpha-2 macroglobulin (α2M) from whole blood (Abst.; [0161]). Hanna teaches that the α2M compositions can be prepared from mammalian samples comprising plasma and can comprise platelets, wherein the red blood cells and white blood cells have been removed from the sample [0015], e.g., plasma. Hanna teaches that the α2M composition can be further enriched for α2M by filtration of the sample with a filter with a molecular weight cutoff of ~500 kDa wherein the α2M composition is retained by the filter, i.e., the α2M is in the retentate, and undesirable proteins less than 500 kDa have been reduced (from the retentate) [0015]. Hanna teaches that the filtration can be performed by centrifugation [0015], which would necessarily entail transferring the plasma, e.g., plasma comprising the α2M, from the separator tube to a centrifuge tube with an integral 500 kDa filter, i.e., an isolator tube, and recovering the retentate, which comprises the α2M, after centrifugation.
Neither Esteron nor Hanna specifically teaches the transfer device and transfer method set forth in claim 1. However, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Esteron in view of Hanna comprising the transfer device and transfer method set forth in claim 1 in view of the disclosures of Mijers and Sealfon.
Mijers teaches a fluid transfer device comprising a syringe port (6) which couples to a transfer syringe, i.e., a syringe port disposed on a first portion of an exterior of a transfer device to enable the transfer syringe and the transfer device to be used cooperatively to perform the transfer of the one or more portions of the plasma, wherein the syringe port (disposed on a first portion of an exterior of the transfer device) is configured to be coupled to an end connector of the transfer syringe while a transfer needle of the transfer syringe is disconnected from the end connector of the transfer syringe; a needle for withdrawing the fluid through the transfer device and into the syringe (8), i.e., a separator tube port disposed on a second portion of the exterior of the transfer device, wherein: the separator tube port comprises a hollow plasma needle that is separate and distinct from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to the syringe port of the transfer device; a venting needle connected to the outside air (9), i.e., the separator tube port comprises a hollow air needle that is separate and distinct from the plasma needle of the transfer device and from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to external air surrounding the exterior of the transfer device; and a housing with a housing insert or inset which does not completely cover the needles ([0015-16] discloses that the needle protector may comprise a centrical surface which may be adapted to be punctured by the needles; hence, it is prima facie obvious for the needle protector to not comprise a centrical surface covering the needles because it is prima facie obvious to not have an optional feature), i.e., the separator tube port comprises a recess that is defined by the second portion of the exterior of the transfer device, that is configured to surround the plasma needle and the air needle and define an opening to limit access to the plasma needle and the air needle without fully covering the plasma needle, and that is configured to receive and surround one end of the separator tube through the opening to cause an interior of the separator tube to become coupled to the syringe port through the plasma needle, and to become coupled to the external air through the air needle, as the separator tube is inserted into the separator tube port through the opening (Abst.; Figs. 1-6; [0045-52]).
Mijers does not teach that the air needle is longer than the plasma needle; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the air needle to be longer than the plasma needle in view of the disclosure of Sealfon.
Sealfon teaches transfer devices comprising 2 needles, one needle (104) connected to a syringe port (110) for withdrawing solution and a longer needle (102) connected to the external air (114), the arrangement of which Sealfon teaches is helpful for reducing foaming (Abst.; Fig. 1A). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to modify Mijers transfer device to comprise an air needle which is longer than the plasma needle to assist in reducing foaming.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to transfer the plasma from the separator to the isolator with the transfer device made obvious by Mijers in view of Sealfon because the transfer device made obvious by Mijers in view of Sealfon would provide protection from needle sticks and would allow the release of pressure or vacuum from the interior of the separator tube to facilitate transfer of the plasma and reduce foaming of the liquid.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Esteron in view of Hanna, Mijers and Sealfon described above wherein transferring one or more portions of the plasma from within the at least one separator tube and into a transfer syringe, wherein transferring the one or more portions of the plasma comprises coupling the transfer syringe to a syringe port disposed on a first portion of an exterior of a transfer device to enable the transfer syringe and the transfer device to be used cooperatively to perform the transfer of the one or more portions of the plasma, wherein the syringe port is configured to be coupled to an end connector of the transfer syringe while a transfer needle of the transfer syringe is disconnected from the end connector of the transfer syringe; with the end connector of the transfer syringe remaining coupled to the syringe port of the transfer device, coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port disposed on a second portion of the exterior of the transfer device, wherein: the separator tube port comprises a hollow plasma needle that is separate and distinct from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to the syringe port of the transfer device; the separator tube port comprises a hollow air needle that is separate and distinct from the plasma needle of the transfer device and from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to external air surrounding the exterior of the transfer device; the separator tube port comprises a recess that is defined by the second portion of the exterior of the transfer device, that is configured to surround the plasma needle and the air needle and define an opening to limit access to the plasma needle and the air needle without fully covering the plasma needle, and that is configured to receive and surround one end of the separator tube through the opening to cause an interior of the separator tube to become coupled to the syringe port through the plasma needle, and to become coupled to the external air through the air needle, as the separator tube is inserted into the separator tube port; and as the separator tube is coupled to the separator tube port through the opening, the air needle extends further toward a cap of the separator tube than the plasma needle to enable the air needle to penetrate the cap before the plasma needle is able to penetrate the cap to enable the interior of the separator tube to become coupled to the external air before becoming coupled to the syringe port, thereby enabling an equalization of air pressure within the interior of the separator tube with air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port; while each separator tube of the at least one separator tube is coupled to the separator tube port, operating a plunger of the transfer syringe to withdraw at least one portion of the one or more portions of the plasma from the separator tube and into the transfer syringe through the plasma needle of the transfer device, and to draw a portion of the external air into the separator tube through the air needle of the transfer device; and following transfer of the one or more portions of the plasma from each separator tube of the at least one separator tube, disconnecting the end connector of the transfer syringe from the syringe port of the transfer device to enable the transfer needle of the transfer syringe to be connected to the end connector of the transfer syringe, and using the transfer syringe, with the transfer needle coupled to the end connector, to inject the one or more portions of the plasma into the at least one isolator; subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator; and administering at least some of the isolated α2M molecules to the patient via inhalation with a nebulizer; therefore, claims 1, 5, 10, 12 and 35 are prima facie obvious.
Esteron teaches that the blood can be autologous to the patient [0055], i.e., wherein the whole blood is drawn from the patient in support of treating the patient with the α2M molecules in an autologous manner; therefore, claim 2 is prima facie obvious.
Esteron teaches that the separator tube can be a vacuum tube, i.e., which is pre-provided with a vacuum therein when in an unused condition, ([0032]; p. 7, claim 33); therefore, claim 6 is prima facie obvious.
Regarding claims 3-4, Esteron teaches drawing the blood into collection tubes wherein the collection tubes can comprise ACD-A [0050-54], but does not specifically state that drawing the whole blood comprises: using a whole blood syringe comprising a hollow needle to draw the whole blood; and partially pre-filling the whole blood syringe with an anticoagulant before using the whole blood syringe to draw the whole blood wherein the anticoagulant comprises a citrate dextrose solution (ACD-A); however, a person of ordinary skill in the art at the time of filing would have found it obvious to draw the blood with a syringe comprising a hollow needle comprising ACD-A because it is an obvious variant using conventional phlebotomy equipment to Esteron’s teaching of drawing the blood into collection tubes comprising ACD-A; therefore, claims 3-4 are prima facie obvious.
Regarding claim 7, Esteron teaches subjecting the separator tube to the centrifugal force comprises placing the separator tube within a holder of a centrifuge (Fig. 2, item 18; [0017]), but Esteron is silent on whether the holder for the separator tubes is a removable holder or a removeable rotor. A person of ordinary skill in the art at the time of filing would have found it obvious for the holder for the separator tubes to be a removable holder configured to be inserted into a bucket of the centrifuge, or an exchangeable rotor of the centrifuge because that would allow the centrifuge to be used for different applications in addition to centrifuging the separator tubes; therefore, claim 7 is prima facie obvious.
Regarding claim 13, Esteron teaches storing the composition enriched for α2M molecules at -80 °C for repeating treatment [0063], but does not specifically state that the composition enriched for α2M molecules stored at -80 °C is in a vial; however, a person of ordinary skill in the art at the time of filing would have found it obvious to place the composition enriched for α2M molecules in a vial (e.g., a cryovial) before storage at -80 °C because compositions are conventionally put into a container such as a vial before being stored at -80 °C; therefore, claim 13 is prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1-7, 10 and 12-13 under 35 U.S.C. 103 over Esteron in view of Mijers, Sealfon and Hanna, Applicant alleges that “there is no possible combination of Esteron, Mijers, Sealfon and Hanna-221 that teaches a transfer device that: 1) is separate and distinct from any component of a syringe; 2) is configured to couple multiple separator tubes (one at a time) to a single transfer syringe; 3) provides a syringe port to enable coupling to an end connector of the transfer syringe while the transfer needle of the transfer syringe is not coupled to that end connector; 4) provides a separator tube port within a recess that defines an opening to receive an end of each separator tube of the one or more separator tubes that is sealed with a cap; and 5) provides the separator tube port with a plasma needle positioned within the recess so as to be accessible only through the opening to prevent needle sticks therewith without needing to be fully covered, and to enable the coupling of each separator tube inserted into the separator tube port to the syringe port.”
Applicant does not present any coherent line of reasoning demonstrating that the transfer device made obvious by Mijers in view of Sealfon is inseparable from any component of a syringe and Mijers discloses a transfer device which connects to the transfer syringe through a typical Luer-Lock end connector (4 in Figs. 2-8; [0046-57]); hence, Applicant’s allegation that the transfer device made obvious by Mijers in view of Sealfon is inseparable from any component of a syringe is completely unpersuasive and in contradiction to what the prior art discloses.
Applicant does not present any coherent line of reasoning demonstrating that the transfer device made obvious by Mijers in view of Sealfon is NOT configured to couple multiple separator tubes (one at a time) to a single transfer syringe. Serially removing the plasma from multiple separator tubes simply involves repeating the process disclosed in Mijers for removing solution from a single tube which a person of ordinary skill in the art at the time of filing would have found it obvious; hence, Applicant’s allegation that the transfer device made obvious by Mijers in view of Sealfon is NOT configured to couple multiple separator tubes (one at a time) to a single transfer syringe is completely unpersuasive and in contradiction to what the prior art discloses.
Applicant does not present any coherent line of reasoning demonstrating that the transfer device made obvious by Mijers in view of Sealfon DOES NOT provide a syringe port to enable coupling to an end connector of the transfer syringe while the transfer needle of the transfer syringe is not coupled to that end connector. Mijers discloses a transfer device which connects to the transfer syringe through a typical Luer-Lock end connector (4 in Figs. 2-8; [0046-57]); hence, Applicant’s allegation that the transfer device made obvious by Mijers in view of Sealfon DOES NOT provide a syringe port to enable coupling to an end connector of the transfer syringe while the transfer needle of the transfer syringe is not coupled to that end connector is completely unpersuasive and in contradiction to what the prior art discloses.
Applicant does not present any coherent line of reasoning demonstrating that the transfer device made obvious by Mijers in view of Sealfon DOES NOT provide a separator tube port within a recess that defines an opening to receive an end of each separator tube of the one or more separator tubes that is sealed with a cap. Mijers discloses a transfer device which comprises a cylindrical housing (25) which is a recess or opening which receives the end of each tube (Figs. 4,6; [0050], [0052]); hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the transfer device made obvious by Mijers in view of Sealfon provides a separator tube port within a recess that defines an opening to receive an end of each separator tube of the one or more separator tubes that is sealed with a cap; thus, Applicant’s allegation that the transfer device made obvious by Mijers in view of Sealfon DOES NOT provide a separator tube port within a recess that defines an opening to receive an end of each separator tube of the one or more separator tubes that is sealed with a cap is completely unpersuasive and in contradiction to what the prior art discloses.
Regarding Applicant’s allegation that the transfer device made obvious by Mijers in view of Sealfon DOES NOT provide a separator tube port with a plasma needle positioned within the recess so as to be accessible only through the opening to prevent needle sticks therewith without needing to be fully covered, and to enable the coupling of each separator tube inserted into the separator tube port to the syringe port, Applicant alleges (pp. 20-22) that Mijers requires that the needles be fully surrounded by a needle protector; however, Mijers teaches [0015-16] that the needle protector may comprise a centrical surface which may be adapted to be punctured by the needles; hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the transfer device can comprise a needle protector which does not comprise a centrical surface covering the needles because it is prima facie obvious to not have an optional feature. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the transfer device made obvious by Mijers in view of Sealfon to provide a separator tube port with a plasma needle positioned within the recess so as to be accessible only through the opening to prevent needle sticks therewith without needing to be fully covered, and to enable the coupling of each separator tube inserted into the separator tube port to the syringe port.
Applicant alleges that the transfer device of Mijers is “such a complex mechanism” as compared to the instant transfer device (pp. 22-24). In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., it’s complexity) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Thus, Applicant’s allegations that the transfer device used in the claimed methods is not obvious over the teachings of Esteron, Mijers, Sealfon and Hanna is unpersuasive.
Applicant alleges (pp. 24-26), without any reasoning or explanation, that “there is no possible combination of Esteron, Mijers, Sealfon and Hanna-221 that teaches a method including all of: 1) subjecting at least one separator tube to a first centrifuging stage to separate plasma from red blood cells and white blood cells of whole blood; 2) transferring portions of the plasma from within the at least one separator tube and into at least one isolator, wherein each isolator of the at least one isolator comprises a filter; and 3) subjecting the at least one isolator to a second centrifuging stage to cause a combination of the filter and centrifugal force to isolate α2M molecules from other components of the plasma.” This is completely unpersuasive as Esteron clearly teaches subjecting at least one separator tube to a first centrifuging stage to separate plasma from red blood cells and white blood cells of whole blood and transferring portions of the plasma from within the at least one separator tube and into at least one isolator and Hanna teaches that the isolator can comprise a filter and subjecting the at least one isolator to a second centrifuging stage to cause a combination of the filter and centrifugal force to isolate α2M molecules from other components of the plasma as set forth in the rejection above. Hence, Applicant’s allegations are undeveloped and thoroughly unpersuasive.
Applicant argues (pp. 24-26) that the plasma cannot be concentrated by centrifugation of a hemoconcentrator. The rejection set forth above does not rely on concentrating plasma by centrifugation of a hemoconcentrator; hence, the allegation is moot.
Hence, the rejection over Esteron in view of Hanna, Mijers and Sealfon is maintained with modification to address claim amendments and for clarity.
Claims 1-7, 10, 12-13, 25-31 and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron in view of Mijers, Sealfon, Hanna and Mitchell, US 3300051 (cite C, PTO-892, 6/13/2024; herein “Mitchell”).
The discussion of Esteron, Mijers, Sealfon and Hanna regarding claims 1-7, 10, 12-13 and 35 set forth in the rejection above is incorporated herein.
Esteron teaches producing α2M-enriched plasma by centrifuging whole blood in a separator tube comprising separator gel ([0007-10], [0031], [0033], [0035-38], [0073]; p. 6, claim 1) wherein the tube can be glass [0051], i.e., transparent, is elongate and is sealed with a penetrable cap ([0052], Fig. 4), i.e., at least one separator tube, wherein each separator tube of the at least one separator tube comprises: an elongate transparent tube that defines an opening at one end that is sealed with a cap that is penetrable to receive whole blood; and an amount of separator gel disposed within the separator tube to cooperate with a first centrifugal force exerted on the separator tube for a first period of time during a first centrifuging stage to separate plasma containing a2M molecules from other components of the whole blood.
Hanna teaches that the α2M-enriched plasma composition, produced by centrifuging whole blood in a separator tube with a separator gel in the method made obvious by Esteron in view of Hanna, can be further enriched for α2M by filtration of the sample with a filter with a molecular weight cutoff of ~500 kDa wherein the α2M composition is retained by the filter, i.e., the α2M is in the retentate, and undesirable proteins less than 500 kDa have been reduced (from the retentate), wherein the filtration can be performed by centrifugation, which would necessarily entail transferring the plasma comprising the α2M from the separator tube to a centrifuge tube with an integral 500 kDa filter, i.e., an isolator tube, and recovering the retentate, which comprises the α2M, after centrifugation.
Neither Esteron, Mijers, Sealfon nor Hanna teach that the isolator tube comprises a first cylinder defined by a first cylindrical wall having a first end that is configured to be closable with a septum cap that is penetrable to receive the plasma containing the α2M molecules following the first centrifuging stage, and having a second end that is closed with the filter; and a second cylinder defined by a second cylindrical wall having a first end that is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and having a second end that defines an opening that is configured to be coupled to the filter in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter, wherein: the filter is configured to cooperate with a second centrifugal force exerted on the isolator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the isolator tube to have such design specifications in view of the disclosure of Mitchell.
Mitchell teaches a centrifuge filter tube comprising a first cylinder defined by a first cylindrical wall and a second cylinder defined by a second cylindrical wall; a first end of the first cylindrical wall of the first cylinder defines an opening that is configured to be closable with a cap, and a second end of the first cylindrical wall is closed with the filter; a first end of the second cylindrical wall of the second cylinder is closed, and the second end of the second cylindrical wall of the second cylinder defines an opening that is configured to be coupled to the second end of the first cylinder in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter (col. 1, ll. 66 – col. 2, ll. 62; Fig. 1). The closed end of the second cylindrical wall appears hemispherical in Fig. 1; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the design of the closed end of the second cylindrical wall to narrow to form a conically-shaped end portion to match complementarily-shaped centrifuge tube rotors or holders.
Hence, it would be obvious for the isolator centrifuge filter tube in the method made obvious by Esteron in view of Mijers, Sealfon and Hanna to have a design comprising a pierceable, resealable cap so that the plasma/PRP can be transferred from the separator tube to the isolator tube with the transfer apparatus made obvious by Mijers in view of Sealfon and wherein the filter has a molecular weight cutoff of about 500 kDa as in the method made obvious by Esteron in view of Mijers, Sealfon and Hanna wherein each isolator of the at least one isolator comprises a first cylinder defined by a first cylindrical wall having a first end that is configured to be closable with a septum cap that is penetrable to receive the plasma containing the α2M molecules following the first centrifuging stage, and having a second end that is closed with the filter; and a second cylinder defined by a second cylindrical wall having a first end that is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and having a second end that defines an opening that is configured to be coupled to the filter in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter, wherein: the filter is configured to cooperate with a second centrifugal force exerted on the isolator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma.
It is prima facie obvious to collect the reagents and equipment of a method into a kit because it would improve the convenience and marketability of the method and it would be obvious to have any number of disposables, such as separator tubes and isolator tubes, because it would allow practicing the method with a number of samples; hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Esteron in view of Mijers, Sealfon, Hanna and Mitchell wherein a kit is provided wherein the kit comprises: a syringe for drawing whole blood, i.e., a whole blood syringe; the at least one separator tube, wherein each separator tube of the at least one separator tube comprises: an elongate transparent tube that defines an opening at one end that is sealed with a cap that is penetrable to receive whole blood; and an amount of separator gel disposed within the separator tube to cooperate with a first centrifugal force exerted on the separator tube for a first period of time during a first centrifuging stage to separate plasma containing α2M molecules from other components of the whole blood; at least one isolator, wherein each isolator of the at least one isolator comprises: a filter; a first cylinder defined by a first cylindrical wall having a first end that is configured to be closable with a septum cap that is penetrable to receive the plasma containing the α2M molecules following the first centrifuging stage, and having a second end that is closed with the filter; and a second cylinder defined by a second cylindrical wall having a first end that is closed where the second cylindrical wall narrows to form a conically-shaped end portion, and having a second end that defines an opening that is configured to be coupled to the filter in a manner that causes a first interior space of the first cylinder and a second interior space of the second cylinder to be separated by the filter, wherein: the filter is configured to cooperate with a second centrifugal force exerted on the isolator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma; the transfer device; and a nebulizer configured to be provided with the a2M molecules isolated during the second centrifuging stage, and to administer the a2M molecules to the patient via inhalation; employing the whole blood syringe to perform the step of drawing the whole blood; employing the at least one separator tube to perform the step of separating plasma containing α2M molecules from the other components of the whole blood; employing the at least one isolator to perform the step of isolating the α2M molecules from the other components of the plasma; and employing the nebulizer to perform the step of administering at least some of the isolated α2M molecules to the patient via inhalation; therefore, claims 25, 31 and 33 are prima facie obvious.
As set forth in a rejection above, a whole blood syringe comprising an amount of an anticoagulant carried within the whole blood syringe to prevent the whole blood from coagulating therein wherein the anticoagulant comprises a citrate dextrose solution (ACD-A) is obvious over the disclosure of Esteron; therefore, claims 26-27 are prima facie obvious.
As set forth in a rejection above, a separator tube which comprises a vacuum separator tube that, when in an unused condition, is pre-provided with a vacuum therein that the seal provided by the cap is used to maintain is obvious over the disclosure of Esteron; therefore, claim 28 is prima facie obvious.
Regarding claims 29-30, the method made obvious by Esteron in view of Mijers, Sealfon, Hanna and Mitchell comprises multiple centrifugation steps with different tubes, separator tubes and isolator tubes; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the kit to comprise a centrifuge that comprises at least one exchangeable rotor to enable the centrifuge to be used in the first centrifuging stage and the second centrifuging stage by exchanging the at least one exchangeable rotor or a centrifuge that comprises: a rotor that defines multiple buckets; and a first set of exchangeable holders and a second set of exchangeable holders, wherein the multiple buckets enable the centrifuge to be used in the first centrifuging stage with the first set of exchangeable holders installed within the multiple buckets, and enable the centrifuge to be used in the second centrifuging stage with the second set of exchangeable holders installed within the multiple buckets; therefore, claims 29-30 are prima facie obvious.
Regarding claim 34, a person of ordinary skill in the art at the time of filing would have found it obvious for the kit to have a dummy isolator so that the centrifuge can be balanced when only one sample in one isolator needs to be processed; therefore, claim 34 is prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. 103 over Esteron in view of Mijers, Sealfon, Hanna and Mitchell, Applicant argues that “Mitchell does not cure the aforedescribed deficiencies of the aforedescribed combination of Esteron, Mijers, Sealfon and Hanna-221...” (p. 26). The alleged deficiencies of Esteron, Mijers, Sealfon and Hanna are addressed on pp. 16-21 above. The rejection is maintained with modification to address claim amendments.
Claims 1-7, 10, 12-13 and 25-35 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron in view of Mijers, Sealfon, Hanna, Mitchell and Aljefri, US 2020/0305781 (cite D, PTO-892, 6/13/2024; herein “Aljefri”).
The discussion of Esteron, Mijers, Sealfon, Hanna and Mitchell regarding claims 1-7, 10, 12-13, 25-31 and 33-34 set forth in the rejection above is incorporated herein.
The method made obvious by Esteron in view of Mijers, Sealfon, Hanna and Mitchell comprises an isolator tube with a septum cap; however, none of Esteron, Mijers, Sealfon, Hanna or Mitchell disclose that the septum cap extends the first cylindrical wall of the first interior space of the isolator. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the septum cap to extend the first cylindrical wall of the first interior space of the isolator in view of the disclosure of Aljefri.
Aljefri teaches a blood collection tube (title, Figs.) including a septum cap (e.g., Fig. 1C #20; par. [0081-0082]) capable of serving as an extension to a cylindrical wall to increase a volume (see Fig. 1C; see also e.g., Figs. 9A-10B and par. [0088] for cases having higher volumes). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Esteron in view of Hanna and Mitchell wherein the septum cap further comprises a third cylindrical wall configured to serve as an extension to the first cylindrical wall to increase a volume of the first interior space when the first end of the first cylindrical wall is closed with the septum cap, in order to accommodate different volume samples as desired; therefore, claim 32 is prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. 103 over Esteron in view of Mijers, Sealfon, Hanna, Mitchell and Aljefri, Applicant argues that “...Aljefri does not cure the aforedescribed deficiencies of the aforedescribed combination of Esteron, Mijers and Hanna-221...” (pp. 26-27). The alleged deficiencies of Esteron, Mijers, Sealfon and Hanna are addressed on pp. 16-21 above. The rejection is maintained with modification to address claim amendments.
Conclusion
No claims are allowed.
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