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 4/23/2026 are acknowledged. Claims 38, 40 and 58-59 are amended; claims 1-37, 44, 48 and 52-54 are canceled; no claims are withdrawn; claims 38-43, 45-47, 49-51 and 55-59 are pending and have been examined on the merits.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 Patent cite 1 and US Patent Application Publication cite 1 are lined through because they are already of record.
Claim Rejections - 35 USC § 112
The rejection of claims 58-59 under 35 U.S.C. § 112(a), as set forth at pp. 2-4 of the previous Office Action, is withdrawn in view of the amendment of the claims.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 38-43, 45-47, 49-51 and 55-59 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 38-43, 45-47, 49-51 and 55-59 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 38-43, 45-47, 49-51 and 55-59 are rejected under 35 U.S.C. 112(a) for not being enabled commensurate in scope with the claims.
Claims 38-43, 45-47, 49-51 and 55-59 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 38 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 39-43, 45-47, 49-51 and 55-59 depend from claim 38; hence, claims 38-43, 45-47, 49-51 and 55-59 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. 2C, 2D and 2G of Applicant's originally filed drawings, and in at least paragraphs [0031]-[0035] and [0042]-[0045] of Applicant's originally filed specification. No new matter has been added” (p. 11).
This is incorrect. Neither FIGS. 2C, 2D and 2G nor [0031]-[0035] and [0042]-[0045] provide support for the limitations. To the contrary, Fig. 2D clearly shows that the air needle (439) 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 38-40, 43, 45-47, 49-50 and 58-59 under 35 U.S.C. § 103(a) over Hanna et al., US 2015/0174221 (cite A, PTO-892, 4/30/2024; herein “Hanna”) in view of Mijers et al., US 2020/0146939 (cite A, attached PTO-892; herein “Mijers”), Sealfon et al., US 2018/0116909 (cite B, attached PTO-892; herein “Sealfon”) and Esteron et al., US 2023/0172989 (cite A, PTO-892, 9/27/2024; herein “Esteron”) as set forth at pp. 8-18 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 38-43, 45-47, 49-51 and 58-59 under 35 U.S.C. § 103(a) over Hanna in view of Mijers, Sealfon, Esteron and Hanna et al., US 20150079194 (cite C, PTO-892, 4/30/2024; herein “Hanna#2”) as set forth at pp. 20-21 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 38-43, 45-47, 49-51, 55 and 57-59 under 35 U.S.C. § 103(a) over Hanna in view of Mijers, Sealfon, Esteron, Hanna#2 and Mitchell, US 3300051 (cite D, PTO-892, 4/30/2024; herein “Mitchell”) as set forth at pp. 21-25 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 38-40, 43, 45-47 and 49-50 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna et al., US 2015/0174221 (cite A, PTO-892, 4/30/2024; herein “Hanna”) in view of “Vacuette blood transfer device”, available since before 4/2/2017 (cite U, PTO-892, 2/19/2025; herein “Vacuette blood transfer device”) and Esteron et al., US 2023/0172989 (cite A, PTO-892, 9/27/2024; herein “Esteron”).
Hanna teaches methods for isolating autologous alpha-2 macroglobulin (α2M) from whole blood from a subject and using the autologous α2M preparation for treating the subject’s synovial joints, spine, tendons or ligaments for the treatment of pain, degeneration or inflammation (Abst.; [0028], [0161], [0231]). Hanna teaches that the administration of the autologous α2M preparation can be by direct injection of the autologous α2M preparation into the subject’s spinal structures, facet joints or diarthrodial joints or by intramuscular injection ([0247], [0285], [0291], [0295]).
Hanna teaches that the α2M compositions can be prepared from mammalian samples, wherein the mammalian sample is from the human subject to be treated (Abst.; [0015]), i.e., autologous, wherein the mammalian sample can comprise plasma and can comprise platelets, wherein the red blood cells and white blood cells have been removed from the sample [0015], e.g., platelet-rich plasma (PRP). Hanna teaches that enriching the biological sample for α2M, wherein the biological sample comprises blood, can comprise centrifugation of the blood to remove red blood cells and white blood cells [0128]. Hanna teaches that red blood cells and white blood cells from the blood sample can be sedimented by centrifugation at ~ 1000 x g ([0147], [0161]) which would necessarily require depositing the blood sample into a centrifugation tube, i.e., a separator tube. Hanna teaches that the biological sample can be collected by a needle-syringe combo [0015].
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 Hanna comprising depositing whole blood into at least one separator tube; subjecting the at least one separator tube to a first centrifugal force in a first centrifuging stage for a first predetermined period of time to cause at least the first centrifugal force to separate plasma of the whole blood within the at least one separator tube from red blood cells and white blood cells of the whole blood within the at least one separator tube, wherein the plasma includes the α2M molecules; and injecting at least a portion of the α2M molecules into a musculoskeletal structure of a patient from which the whole blood was drawn.
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., platelet-rich 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.
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 Hanna further comprising transferring one or more 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 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, retrieving at least the portion of the α2M molecules from within the at least one isolator prior to injecting at least the portion of the α2M molecules into the musculoskeletal structure of the patient from which the whole blood was drawn.
Thus, Hanna teaches the method of claim 38 except that Hanna does not specifically teach the transfer device and transfer method set forth in claim 38. However, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of Hanna comprising the transfer device and transfer method set forth in claim 38 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 plasma needle as the plasma needle penetrates the cap, wherein the recess is the sole component of the transfer device that is configured to limit access to the plasma needle, and no component of the transfer device is configured to cover the plasma needle, wherein the plasma 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 plasma needle penetrates the cap; and wherein the plasma 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 plasma 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 made obvious by Hanna described above wherein the transfer of the plasma from the separator tube comprising a separator gel, to the isolator tube comprises transferring the plasma from the separator to the isolator with the transfer device made obvious by “Vacuette blood transfer device”; therefore, claims 38-39, 45 and 59 are prima facie obvious.
Esteron teaches methods for treating conditions or disorders 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 ([0013], [0071-72]; p. 6, claim 11). 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 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).
Esteron teaches that the separator tube can comprise a glass tube [0051], i.e., transparent, wherein the tube is an elongate tube that defines an opening at one end that is sealed with a cap (Fig. 4) wherein the cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn (Fig. 4; [0052]); 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 Hanna in view of Esteron 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; the cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; and depositing the whole blood into at least one separator tube comprises: inserting the hollow needle of the syringe through the cap of each separator tube of the at least one separator tube; and providing at least a portion of the whole blood into each separator tube of the at least one separator tube through the hollow needle; therefore, claims 40, 43 and 58 are prima facie obvious.
Centrifuge tubes should clearly be centrifuged in the appropriately sized holder or rotor; 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 Hanna in view of Esteron wherein subjecting the at least one separator tube to the first centrifugal force in the first centrifuging stage comprises placing the at least one separator tube within a first holder of a centrifuge, and operating the centrifuge to exert the first centrifugal force on the at least one separator tube; and subjecting the at least one isolator to the second centrifugal force in the second centrifuging stage comprises placing the at least one isolator within a second holder of the centrifuge, and operating the centrifuge to exert the second centrifugal force on the at least one isolator; wherein: the first holder comprises either a first removable holder configured to be inserted into a bucket of the centrifuge, or a first exchangeable rotor of the centrifuge; and the second holder comprises either a second removable holder configured to be inserted into a bucket of the centrifuge, or a second exchangeable rotor of the centrifuge; therefore, claims 46-47 are prima facie obvious. NOTE: the claims do not recite that the first holder cannot be identical to the second holder nor that the first rotor cannot be identical to the second rotor.
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 Hanna wherein: the at least one separator tube, the centrifuge, the transfer syringe and the at least one isolator, together, form a kit for isolating the α2M molecules from the whole blood; and multiple versions of the kit are defined by at least one of a quantity of separator tubes included in the at least one separator tube and a quantity of isolators included in the at least one isolator, wherein the multiple versions of the kit include a kit comprising 4, 8 or 16 separator tubes; therefore, claims 49-50 are prima facie obvious.
Response to Arguments
Regarding the rejection of claims 38-40, 43, 45-47, 49-50 and 58 under 35 U.S.C. §103 over Hanna in view of Mijers, Sealfon and Esteron, Applicant argues (pp. 15-24) 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 38-43, 45-47 and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of “Vacuette blood transfer device”, Esteron and Hanna et al., US 20150079194 (cite C, PTO-892, 4/30/2024; herein “Hanna#2”).
The discussion of Hanna, “Vacuette blood transfer device” and Esteron regarding claims 38-40, 43 and 45-47 and 49-50 set forth in the rejection above is incorporated herein.
Hanna teaches that the autologous blood composition enriched for α2M can comprise the anticoagulant acid-citrate-dextrose (ACD-A) ([0015], [0121], [0350]), but Hanna and Esteron do not specifically teach that the whole blood is withdrawn from the subject with a syringe partially filled with an ACD-A anticoagulant solution; however, a person of ordinary skill in the art at the time of filing would have found it obvious to do so in view of Hanna#2.
Hanna#2 also teaches methods of producing therapeutic autologous α2M compositions for administration to a subject (Abst.). Hanna#2 teaches embodiments wherein syringes are pre-loaded with a volume of sterile ACD-A anticoagulant, whole blood is drawn from the patient into the syringe containing the anticoagulant and the blood with anticoagulant is transferred to a centrifuge tube to produce plasma from the patient’s blood [0457-463]. 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 Hanna in view of Esteron comprising: using the syringe to draw the whole blood from the patient; and partially pre-filling the syringe with an anticoagulant before using the syringe to draw the whole blood from the patient wherein the anticoagulant comprises a citrate dextrose solution (ACD-A); therefore, claims 41-42 are prima facie obvious.
Regarding claim 51, Hanna#2 teaches balancing the centrifuge with another tube with 47.7 ml of water to counterbalance the separator tube with 45 ml of whole blood with ACD-A because the specific density of blood is ~1.06 [0463]; 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 Hanna in view of Esteron wherein the kit further includes a dummy isolator of a shape and size similar to the at least one separator tube to provide a counterbalance to the weight of a single separator tube of the at least one separator tube after the single separator tube is filled with plasma to enable balancing of the centrifuge; therefore, claim 51 is prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. 103 over Hanna-221 in view of Mijers, Sealfon, Esteron and Hanna-194 (US 2015/0079194), Applicant argues that “Hanna-194 does not cure the aforedescribed deficiencies of the aforedescribed combination of Hanna-221, Mijers, Sealfon and Esteron...” (p. 25). The rejection set forth above does not rely on Mijers or Sealfon; hence, the argument is moot.
Claims 38-43, 45-47, 49-51, 55 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of “Vacuette blood transfer device”, Esteron, Hanna#2 and Mitchell, US 3300051 (cite D, PTO-892, 4/30/2024; herein “Mitchell”).
The discussion of Hanna, “Vacuette blood transfer device”, Esteron and Hanna#2 regarding claims 38-43, 45-47 and 49-51 set forth in the rejection above is incorporated herein.
As set forth above, the method made obvious by Hanna comprises transferring one or more 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 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, retrieving at least the portion of the α2M molecules as the retentate from within the at least one isolator prior to injecting at least the portion of the α2M molecules into the musculoskeletal structure of the patient from which the whole blood was drawn; and comprises transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; and using the transfer syringe to deposit the one or more portions of the plasma into the at least one isolator; and the method made obvious by Hanna in view of Esteron makes obvious using septum caps on tubes wherein at least a portion of the septum cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn, but the disclosures of Hanna, Esteron and Hanna#2 do not specifically disclose an isolator tube that is a form that comprises 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 septum 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 where the second cylindrical wall narrows to form a conically-shaped end portion, 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. 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 a form 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 septum 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 where the second cylindrical wall narrows to form a conically-shaped end portion, 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 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 where the second cylindrical wall narrows to form a conically-shaped end portion, 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).
Hence, it would be obvious for the isolator centrifuge filter tube in the method made obvious by Hanna in view of Esteron and Hanna#2 to comprise a pierceable, resealable cap as taught by Esteron so that the plasma can be transferred from the separator tube to the isolator tube with the transfer syringe of the method made obvious by Hanna in view of Esteron and wherein the filter has a molecular weight cutoff of about 500 kDa as in the method made obvious by Hanna in view of Esteron wherein each isolator of the at least one isolator comprises 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 septum 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 where the second cylindrical wall narrows to form a conically-shaped end portion, 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; at least a portion of the septum cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn; transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator comprises: using a transfer syringe to withdraw the one or more portions of the plasma from within the at least one separator tube; inserting a needle of the transfer syringe through the septum cap of each isolator of the at least one isolator; and injecting the one or more portions of the plasma into the first interior space from within the transfer syringe; and isolating the α2M molecules from other components of the plasma within the at least one isolator comprises isolating the α2M molecules from other components within the first interior space of each isolator of the at least one isolator from the other components of the plasma within the second interior space of each isolator of the at least one isolator wherein the filter of each isolator of the at least one isolator has a molecular weight cut off ranging from 100 kDa to 500 kDa, because using a septum cap on the isolator tubes wherein at least a portion of the septum cap is formed from a flexible material that allows a hollow needle of a syringe to penetrate therethrough while sealing around the hollow needle, and that re-seals after the hollow needle is withdrawn would allow the isolator tube to be used in the method made obvious by Hanna in view of Esteron; therefore, claims 55 and 57 are prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. 103 over Hanna-221 in view of Mijers, Sealfon, Esteron, Hanna-194 and Mitchell, Applicant argues that “Mitchell does not cure the aforedescribed deficiencies of the aforedescribed combination of Hanna-221, Mijers, Sealfon, Esteron and Hanna-194...” (p. 25). The rejection set forth above does not rely on Mijers or Sealfon; hence, the argument is moot.
Claims 38-43, 45-47, 49-51 and 55-57 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of “Vacuette blood transfer device”, Esteron, Hanna#2, Mitchell and Aljefri, US 20200305781 (cite E, PTO-892, 4/30/2024; herein “Aljefri”).
The discussion of Hanna, “Vacuette blood transfer device”, Esteron, Hanna#2 and Mitchell regarding claims 38-43, 45-47, 49-51, 55 and 57 set forth in the rejection above is incorporated herein.
The method made obvious by Hanna in view of Esteron, Hanna#2 and Mitchell comprises an isolator tube with a septum cap; however, none of Hanna, Esteron, Hanna#2 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 Hanna in view of Esteron, Hanna#2, 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 56 is prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. 103 over Hanna-221 in view of Mijers, Sealfon, Esteron, Hanna-194, Mitchell and Aljefri (US 2020/0305781), Applicant argues that “Aljefri does not cure the aforedescribed deficiencies of the aforedescribed combination of Hanna-221, Mijers, Sealfon, Esteron, Hanna-194 and Mitchell...” (pp. 25-26). The rejection set forth above does not rely on Mijers or Sealfon; hence, the argument is moot.
Claims 38-40, 43, 45-47, 49-50 and 58-59 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of “Vacuette blood transfer device”, Esteron 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 1-6, 8-12 and 23-25 set forth in the rejection above is incorporated herein.
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); however, 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 plasma 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 plasma 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 plasma 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 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 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 for each separator tube of the at least one separator tube to comprise a vacuum separator tube that is pre-provided with a vacuum therein when in an unused condition and 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, i.e., at least partial equalization of air pressure between the separator tube and the external air, to facilitate transfer of the plasma and reduce foaming of the liquid.
Thus, the method made obvious by Hanna in view of “Vacuette blood transfer device” and Esteron 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 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; 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 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 at least partial 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 plasma 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 58-59 are prima facie obvious.
Double Patenting
The provisional rejection of claims 39-41, 46, 49, 51 and 55-59 on the ground of nonstatutory double patenting over claims 1-5, 23-24 and 26-30 of copending Application No. 18/909731 (herein “’731”) in view of Hanna, as set forth at pp. 27-29 of the previous Office Action, is withdrawn in view of the approval of the terminal disclaimer over ‘731.
The provisional rejection of claims 38-41, 49 and 55-58 on the ground of nonstatutory double patenting over claims 1-2, 5-6, 21-22 and 24-26 of copending Application No. 18/909762 (herein “’762”), as set forth at p. 30 of the previous Office Action, is withdrawn in view of the approval of the terminal disclaimer over ‘762.
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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