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 Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 4/9/2026 are acknowledged. Claims 1, 21 and 27-28 are amended; claims 8-9 and 15-20 are canceled; no claims are withdrawn; claims 1-7, 10-14 and 21-28 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statement submitted on 12/4/2025 has been considered by the examiner. US Patents cite 1 and US Patent Application Publications cite 1 are lined through because they are already of record.
Claim Objections
Claims 21 and 24 are objected to because of the following informalities:
Claims should be complete sentences ending with periods. Claims 21 and 24 do not end with periods. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The rejection of claims 27-28 under 35 U.S.C. § 112(a), as set forth at pp. 3-4 of the previous Office Action, is withdrawn in view of the amendment of the claims.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.
Claims 1-7, 10-14 and 21-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the method wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening and wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap wherein the transfer device does not comprise an air needle, does not reasonably provide enablement for the method wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening and wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap wherein the transfer device comprises an air needle which extends further toward the cap of the separator tube than the PPP needle to enable the air needle to penetrate the cap before the PPP needle is able to penetrate the cap because the air needle would necessarily also interact with the separator tube in a manner that resists insertion of the end of the separator tube through the opening and interact with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the air needle and cap while still penetrating the cap.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
The claims are not overly broad (factor a). The nature of the invention is biotechnology, i.e., the physiological arts (factor b), which are known to be unpredictable (MPEP 2164.03; factor e); however, the skill of the ordinary artisan in such arts is generally high (usually Ph. D. level; factor d). There is no prior art (factor c) which discloses a transfer device which comprises two needles, one for passing external air into the separator tube (air needle) which is longer than the other needle (PPP needle) which is for passing the liquid content of the separator tube into the transfer syringe WHEREIN the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening and wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap. Hence, a person of ordinary skill in the art at the time of filing would have necessarily had to rely on the direction (factor f) and working examples (factor g) provided by the inventor to practice the invention without undue experimentation (factor h).
Applicant does not provide any direction and working examples of a transfer device which comprises two needles, one for passing external air into the separator tube (air needle) which is longer than the other needle (PPP needle) which is for passing the liquid content of the separator tube into the transfer syringe WHEREIN the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening and wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap. Thus, a person of ordinary skill in the art at the time of filing would have had to engage in undue experimentation (factor h) to practice the methods of claims 1-7, 10-14 and 21-28 with a transfer device which comprises two needles, one for passing external air into the separator tube (air needle) which is longer than the other needle (PPP needle) which is for passing the liquid content of the separator tube into the transfer syringe WHEREIN the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening and wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap, if they are enabled at all; therefore, claims 1-7, 10-14 and 21-28 are rejected under 35 U.S.C. 112(a) for not being enabled commensurate in scope with the claims.
Claims 1-7, 10-14 and 21-28 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 claims contain 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.
The limitations of claim 1 that “the recess is the sole component of the transfer device that is configured to limit access to the PPP needle, and no component of the transfer device is configured to cover the PPP needle; the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening, and does so as the PPP needle penetrates the cap; and the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap” constitute new matter because the limitations are not disclosed in the original disclosure.
MPEP 2173.05(i) is clear that negative limitations must have a basis in the original disclosure and that the mere absence of a positive recitation is not sufficient basis for an exclusionary limitation:
“Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). In describing alternative features, the applicant need not articulate advantages or disadvantages of each feature in order to later exclude the alternative features. See Inphi Corporation v. Netlist, Inc., 805 F.3d 1350, 1356-57, 116 USPQ2d 2006, 2010-11 (Fed. Cir. 2015). The mere absence of a positive recitation is not basis for an exclusion. However, a lack of literal basis in the specification for a negative limitation may not be sufficient to establish a prima facie case for lack of descriptive support. Ex parte Parks, 30 USPQ2d 1234, 1236 (Bd. Pat. App. & Inter. 1993). "Rather, as with positive limitations, the disclosure must only 'reasonably convey[] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.' ... While silence will not generally suffice to support a negative claim limitation, there may be circumstances in which it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure." Novartis Pharms. Corp. v. Accord Healthcare, Inc., 38 F.4th 1013, 2022 USPQ2d 569 (Fed. Cir. 2022) (quoting Ariad Pharm. Inc. v. Eli Lilly & Co., 589 F.3d 1336, 1351, 94 USPQ2d 1161, 1172). Any claim containing a negative limitation which does not have basis in the original disclosure should be rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. See MPEP § 2163 - § 2163.07(b) for a discussion of the written description requirement of 35 U.S.C. 112(a) and pre-AIA 35 U.S.C. 112, first paragraph”.
Claims 2-6, 8-12 and 23-31 depend from claim 1; hence, claims 1-6, 8-12 and 23-31 constitute new matter and are rejected under 35 U.S.C. 112(a) for failing to comply with the written description requirement.
Response to Arguments
Applicant's arguments filed 4/9/2026 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on pp. 11-26 regarding the rejections under 35 U.S.C. § 112(a) and 103 are moot as the rejections have been withdrawn. Regarding the claim amendments, Applicant alleges that “Support for these amendments may be found in at least FIGS. 2A and 2C-E of Applicant's originally filed drawings, and in at least paragraphs [0044]-[0049] and [0054]-[0060] of Applicant's originally filed specification. No new matter has been added” (p. 11).
This is incorrect. Neither FIGS. 2A and 2C-E nor [0044]-[0049] and [0054]-[0060] provide support for the limitations. To the contrary, Fig. 2E clearly shows that the air needle (1329) interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening, and does so as the air needle penetrates the cap; and interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the air needle and cap while still penetrating the cap; hence, the PPP needle is NOT the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening as the PPP needle penetrates the cap; and the PPP needle is NOT the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port with friction between the PPP needle and cap while still penetrating the cap.
Applicant’s allegation of support for the amended limitations is unpersuasive; hence, the claims are rejected for constituting new matter above.
Claim Rejections - 35 USC § 103
The rejection of claims 1-7, 10-14, 21-23 and 27-28 under 35 U.S.C. § 103(a) over Esteron et al., US 2023/0172989 (cite A, PTO-892, 2/14/2025; herein “Esteron”) in view of Hanna et al., US 2015/0174221 (cite B, PTO-892, 2/14/2025; herein “Hanna”), Mijers et al., US 2020/0146939 (cite A, PTO-892, 6/24/2025; herein “Mijers”) and Sealfon et al., US 2018/0116909 (cite B, PTO-892, 6/24/2025; herein “Sealfon”) as set forth at pp. 7-19 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-7, 10-14, 21-24 and 26-28 under 35 U.S.C. § 103(a) over Esteron in view of Hanna, Mijers, Sealfon and Mitchell, US 3300051 (cite C, PTO-892, 2/14/2025; herein “Mitchell”) as set forth at pp. 24-26 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-7, 9-14 and 21-28 under 35 U.S.C. § 103(a) over Esteron in view of Hanna, Mijers, Sealfon, Mitchell and Aljefri, US 2020/0305781 (cite D, PTO-892, 2/14/2025; herein “Aljefri”) as set forth at pp. 27-28 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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, 10-14 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron et al., US 2023/0172989 (cite A, PTO-892, 2/14/2025; herein “Esteron”) in view of Hanna et al., US 2015/0174221 (cite B, PTO-892, 2/14/2025; herein “Hanna”) and “Vacuette blood transfer device”, available since before 4/2/2017 (cite U, PTO-892, 2/21/2025; herein “Vacuette blood transfer device”).
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]) wherein the blood can be from a non-autologous donor [0050], 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), thus producing “platelet poor plasma”, i.e., PPP, 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) wherein the donor and patient are different individuals [0050]. Esteron teaches that the respiratory condition can entail lung damage [0013]. Esteron teaches that separating the plasma from other components of the whole blood comprises: depositing the whole blood into a separator tube, wherein the separator tube contains an amount of separator gel; and subjecting the separator tube to a centrifugal force for a predetermined period of time to cause a combination of the 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), the plasma composition removed from above the separator gel after centrifugation in Esteron constitutes PPP because the plasma composition is produced by the method set forth in the instant disclosure and claims.
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, wherein the red blood cells, white blood cells and platelets have been removed from the sample [0015], i.e., platelet poor 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 (MWCO) 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., PPP, comprising the α2M, from the separator tube to a centrifuge tube with an integral 500 kDa filter, i.e., an aggregator, and recovering the retentate, which comprises the α2M, after centrifugation, i.e. filtering the waste plasma from the PPP comprising transferring the PPP from the transfer syringe and into at least one aggregator, wherein each aggregator of the at least one aggregator comprises a filter; and subjecting the at least one aggregator 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 aggregator of the at least one aggregator to filter the waste plasma from the PPP to generate the aggregate within the at least one aggregator.
Hence, Esteron in view of Hanna make obvious the method of claim 1 except for the transfer device. 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 “Vacuette blood transfer device”.
A person of ordinary skill in the art at the time of filing would have found it obvious to use commercially available liquid transfer devices such as a Vacuette blood transfer device (see “Vacuette blood transfer device”, pp. 1-2) to transfer the plasma from the separator tube sealed with a penetrable cap into the transfer syringe because the Vacuette blood transfer device comprises a male Luer lock (syringe port of the transfer device; top of figure on p. 2) which mates to the female Luer lock connector of traditional syringes and engages blood tubes, e.g., a Vacutainer separator gel tube used as separator, via a shielded enclosure shaped to surround the blood tube comprising a hollow needle to enter the blood tube via the penetrable septum, (separator tube port of the transfer device; lower part of figure on p. 2), i.e., the transfer device comprises a recess configured to receive, through the opening, and surround one end of, the separator tube that is sealed with a cap formed from self-sealing material, wherein insertion of the end of the separator tube through the opening causes an interior of the separator tube to become coupled to the syringe port through the PPP needle as the PPP needle penetrates the cap, wherein the recess is the sole component of the transfer device that is configured to limit access to the PPP needle, and no component of the transfer device is configured to cover the PPP needle, wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening, and does so as the PPP needle penetrates the cap; and wherein the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method for treating a medical condition of a patient with at least alpha-2 macroglobulin (α2M) molecules in an allogeneic or xenogeneic manner made obvious by Esteron in view of Hanna and “Vacuette blood transfer device” comprising drawing whole blood from a donor; depositing the whole blood into at least one separator tube; within the at least one separator tube, separating PPP containing α2M molecules from other components of the whole blood, transferring the PPP to an aggregator; filtering waste plasma from the one or more portions of the PPP transferred into the transfer syringe to generate an aggregate of the α2M molecules; and administering at least some of the aggregate to the patient via injection or inhalation, wherein the donor and the patient are different individuals; wherein the transfer of the PPP from the separator tube comprising a separator gel, to the centrifuge tube with an integral 500 kDa filter, i.e., aggregator, comprises transferring one or more portions of the PPP from within the at least one separator tube and into at least one aggregator, wherein each aggregator of the at least one aggregator comprises a 500 kDa MWCO filter, and administering at least some of the α2M-enriched plasma, i.e., aggregate, to the patient via inhalation with a nebulizer, wherein transferring the one or more portions of the PPP 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 PPP, 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 PPP 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 recess that is defined by the second portion of the exterior of the transfer device, that is configured to surround the PPP needle and define an opening to limit access to the PPP needle without fully covering the PPP needle; the recess is configured to receive, through the opening, and surround one end of, the separator tube that is sealed with a cap formed from self-sealing material; insertion of the end of the separator tube through the opening causes an interior of the separator tube to become coupled to the syringe port through the PPP needle as the PPP needle penetrates the cap; the recess is the sole component of the transfer device that is configured to limit access to the PPP needle, and no component of the transfer device is configured to cover the PPP needle; the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists insertion of the end of the separator tube through the opening, and does so as the PPP needle penetrates the cap; and the PPP needle is the sole component of the transfer device that interacts with the separator tube in a manner that resists removal of the end of the separator tube from the separator tube port, and does so with friction between the PPP needle and cap while still penetrating the cap; and 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 PPP from the separator tube and into the transfer syringe through the PPP needle of the transfer device; and following transfer of the one or more portions of the PPP 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; therefore, claims 1-3, 6-7 and 12 are prima facie obvious.
Regarding claim 4, a person of ordinary skill in the art at the time of filing would have found it obvious that the method could be used for veterinary applications wherein the donor and patient are not the same species because Esteron teaches using blood from a donor or a non-autologous source [0050]; therefore, claim 4 is prima facie obvious.
Regarding claim 5, 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 from the donor comprises: using a whole blood syringe comprising a hollow needle to draw the whole blood from the donor; and partially pre-filling the whole blood syringe with an anticoagulant before using the whole blood syringe to draw the whole blood from the donor; 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, claim 5 is prima facie obvious.
Regarding claims 10-11, Hanna teaches that the α2M molecules can be further purified from the α2M enriched plasma, i.e., PPP, by transferring the plasma from the at least one separator tube and into an α2M reservoir; and using a peristaltic pump to circulate the plasma among the α2M reservoir, a cross-flow filter with a molecular weight cut off (MWCO) of 500 kDa and a waste bag to cause other components of the plasma to pass through the 500 kDa MWCO cross-flow filter and into the waste bag, while the α2M molecules remain within the α2M reservoir ([0018-22], [0153-158], [0164-166]).
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, “Vacuette blood transfer device” comprising transferring one or more portions of the plasma, i.e., PPP, containing α2M molecules in the method made obvious by Esteron in view of Hanna, “Vacuette blood transfer device” from within the separator tube and into an α2M reservoir; and using a peristaltic pump to circulate the plasma among the α2M reservoir, a 500 kDa MWCO cross-flow filter and a waste bag to cause other components of the plasma to pass through the 500 kDa MWCO cross-flow filter and into the waste bag, while the α2M molecules remain within the α2M reservoir because Hanna teaches further purifying the α2M molecules from the α2M enriched plasma by transferring the plasma into an α2M reservoir, using a peristaltic pump to circulate the plasma from the α2M reservoir through a 500 kDa MWCO cross-flow filter wherein other components of the plasma smaller than 500 kDa pass through the cross-flow filter and into the waste bag, while the α2M molecules remain within the α2M reservoir; therefore, claims 10-11 are prima facie obvious.
Esteron teaches storing the composition enriched for α2M molecules at -80 °C for repeating treatment [0063]; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the method made obvious by Esteron in view of Hanna and “Vacuette blood transfer device” to further comprise the step of storing the isolated α2M molecules in a freezing environment prior to administering the at least some of the isolated α2M molecules to the patient; therefore, claim 13 is prima facie obvious.
Regarding claim 14, the concentrated plasma retained in the aggregator would necessarily comprise serum albumin molecules and serotransferrin molecules along with the α2M molecules because the method made obvious by Esteron in view of Hanna, “Vacuette blood transfer device” meets the limitations set forth in the instant disclosure and claims, specifically, the cutoff of the filter is 500 kDa MWCO; hence, the aggregator with a 500 kDa filter would retain serum albumin molecules and serotransferrin molecules along with the α2M molecules; therefore, claim 14 is prima facie obvious.
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 PPP containing α2M molecules from other components of the whole blood; therefore, claim 21 is prima facie obvious.
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 aggregators, 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 Hanna, “Vacuette blood transfer device” wherein a kit is provided wherein the kit comprises: the at least one separator tube, a centrifuge, the transfer device, the transfer syringe, at least one aggregator and a nebulizer; therefore, claims 22-23 are prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1-7, 10-14, 21-23 and 27-28 under 35 U.S.C. §103, Applicant argues (pp. 15-25) that Mijers in view of Sealfon does not meet the limitations drawn to the transfer device. Neither Mijers nor Sealfon are relied on in the rejection set forth above; hence, the arguments are moot.
Claims 1-7, 10-14, 21-24 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron in view of Hanna, “Vacuette blood transfer device” and Mitchell, US 3300051 (cite C, PTO-892, 2/14/2025; herein “Mitchell”).
The discussion of Esteron, Hanna and “Vacuette blood transfer device” regarding claims 1-7, 10-14 and 21-23 set forth in the rejection above is incorporated herein.
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 and “Vacuette blood transfer device”, 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, e.g., platelet-rich plasma comprising the α2M, from the separator tube to a centrifuge tube with an integral 500 kDa filter, i.e., an aggregator, and recovering the retentate, which comprises the α2M, after centrifugation.
Neither Esteron nor Hanna teach that the aggregator 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 aggregator 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 aggregator 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 aggregator in the method made obvious by Esteron in view of “Vacuette blood transfer device” and Hanna to have a design comprising a pierceable, resealable cap so that the α2M-enriched PPP can be transferred from the separator tube to the aggregator with the transfer device made obvious by Esteron in view of Hanna and “Vacuette blood transfer device” and wherein the filter has a molecular weight cutoff of about 500 kDa as in the method made obvious by Esteron in view of Hanna and “Vacuette blood transfer device” wherein each aggregator of the at least one aggregator 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 PPP 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 aggregator for a second period of time during a second centrifuging stage to isolate the α2M molecules from other components of the plasma; therefore, claims 24 and 26 are prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. 103 over Esteron in view of Hanna, Mijers, Sealfon and Mitchell, Applicant argues that “Mitchell does not cure the aforedescribed deficiencies of the aforedescribed combination of Esteron, Hanna-221, Mijers and Sealfon...” (p. 25). The rejection set forth above does not rely on Mijers or Sealfon; hence, the argument is moot.
Claims 1-7, 9-14 and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron in view of Hanna, “Vacuette blood transfer device”, Mitchell and Aljefri, US 2020/0305781 (cite D, PTO-892, 2/14/2025; herein “Aljefri”).
The discussion of Esteron, Hanna, “Vacuette blood transfer device” and Mitchell regarding claims 1-7, 9-14, 21-24 and 26 set forth in the rejection above is incorporated herein.
The method made obvious by Esteron in view of Hanna, “Vacuette blood transfer device” and Mitchell comprises an aggregator with a septum cap; however, none of Esteron, Hanna, “Vacuette blood transfer device” or Mitchell disclose that the septum cap extends the first cylindrical wall of the first interior space of the aggregator. 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 aggregator 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, “Vacuette blood transfer device” 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 25 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, Hanna-221, Mijers, Sealfon and Mitchell...” (p. 25). The rejection set forth above does not rely on Mijers or Sealfon; hence, the argument is moot.
Claims 1-7, 10-14, 21-23 and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Esteron in view of Hanna, “Vacuette blood transfer device” and Sealfon et al., US 2018/0116909 (cite B, PTO-892, 6/24/2025; herein “Sealfon”).
The discussion of Esteron, Hanna and “Vacuette blood transfer device” regarding claims 1-7, 10-14 and 21-23 set forth in the rejection above is incorporated herein.
None of Esteron, Hanna or “Vacuette blood transfer device” teach that the separator tube port also comprises a hollow air needle that is separate and distinct from the PPP needle of the transfer device and from the transfer needle of the transfer syringe wherein the air needle extends further toward the cap of the separator tube than the PPP needle; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the transfer device to further comprise a hollow air needle that is separate and distinct from the PPP needle of the transfer device and from the transfer needle of the transfer syringe wherein the air needle extends further toward the cap of the separator tube than the PPP 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 for the transfer device to further 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 “Vacuette blood transfer device” in view of Sealfon because the transfer device made obvious by “Vacuette blood transfer device” in view of Sealfon 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.
Thus, the method made obvious by Esteron in view of Hanna and “Vacuette blood transfer device” would further comprise using the transfer device made obvious by “Vacuette blood transfer device” in view of Sealfon which is configured to receive and surround one end of the separator tube within the recess to cause an interior of the separator tube to become coupled to the syringe port through the PPP 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; and 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 PPP needle to enable the air needle to penetrate the cap before the PPP 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, operating the 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 PPP needle of the transfer device further comprises operating the plunger of the transfer syringe to draw a portion of the external air into the separator tube through the air needle of the transfer device; therefore, claims 27-28 are prima facie obvious.
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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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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