DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/21/2025 has been entered.
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 9/17/2025 are acknowledged. Claims 38 and 58 are amended; claims 1-37, 44, 48 and 52-54 are canceled; no claims are withdrawn; claim 59 is new; claims 38-43, 45-47, 49-51 and 55-59 are pending and have been examined on the merits.
Claim Rejections - 35 USC § 112
The rejection of claims 38-43, 45-47, 49-51 and 55-57 under 35 U.S.C. § 112(a), as set forth at pp. 4-7 of the previous Office Action is withdrawn in view of the amendment of the claims.
The rejection of claim 58 under 35 U.S.C. § 112(b), as set forth at p. 11 of the previous Office Action is withdrawn in view of the amendment of the claim.
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 58-59 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 claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 59 constitutes new matter because the original disclosure does not disclose that the transferring the one or more portions of the plasma comprises: “as the separator tube is coupled to the separator tube port, the air needle extends further toward a cap of the separator tube than the plasma needle to enable the air needle to penetrate the cap before the plasma needle is able to penetrate the cap to enable the interior of the separator tube to become coupled to the external air before becoming coupled to the syringe port, thereby enabling an equalization of air pressure within the interior of the separator tube with air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port”; hence, claim 59 constitutes new matter and is rejected under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter.
Additionally, claim 58 recites “the equalization of the air pressure within the interior of the separator tube with the air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port comprises a removal of the vacuum prior to the interior of the separator tube becoming coupled to the syringe port” which is not disclosed in the original disclosure and constitutes new matter. Hence, claim 58 is separately rejected under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter.
Response to Arguments
Applicant's arguments filed 11/21/2025 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on p. 15 regarding the rejection under 35 U.S.C. § 112(b) is moot as the rejection has been withdrawn.
Regarding the rejection under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter, Applicant alleges (Remarks received 11/21/2025, pp. 12-15) that the portions of claims 58-59 identified as new matter above are not new matter. Applicant argues that drawings can provide written description; however, none of the instant drawings provide written description for the method steps identified as new matter above. As discussed in the previous Office action and documented below, the original specification discloses the simultaneous equalization of pressures between the separator tube, transfer syringe and external air (see below) NOT an equalization of pressure between the separator tube and the external air followed by an equalization with the transfer syringe; hence, the new matter rejection is maintained with regard to claims 58-59.
[0032] of the original specification discloses “As is about to be described, each of the different types of transfer device 400a and 400b is configured to configured to enable external air 990 surrounding the transfer device 400a or 400b to be drawn in through the air filter 450 at the filtered air port 490 and conveyed to a separator tube 300a or 300b coupled to the separator tube port 430 as part enabling plasma 113 to be transferred from the separator tube 300a or 300b to the transfer syringe 600 coupled to the syringe port 460” (emphasis added); thus, external air is equilibrated with the interior of the separator tube when the tube is coupled to the separator tube port, not before.
[0034] of the original specification discloses “FIG. 2D depicts aspects of the manner in which the dual-flow device 400a enables a simultaneous transfer of filtered air 994 into a separator container 300a or 300b, and of plasma 113 out of the separator container 300a or 300b as part of transferring plasma 994 to the transfer syringe 600. As depicted, the separator tube port 430 may incorporate both an air needle 439 and a plasma needle 431 that are each positioned to penetrate through the cap 310 of a separator tube 300a or 300b to enable the flow through each of gases and/or liquids into and/or out of such a separator tube 300a or 300b.” (emphasis added); thus, the transfer of external air into the separator tube and withdrawal of plasma from the separator tube is simultaneous, NOT that the air goes in before the plasma is withdrawn.
[0035] of the original specification discloses “As depicted, with a separator tube 300a or 300b coupled to the separator tube port 430 such that the needles 431 and 439 penetrate the cap 310 thereof, and with the end connector 610 of the transfer syringe 600 coupled to the syringe port 460, there may be an initial equalization of pressures thereamong. More specifically, and especially where a vacuum separator tube 300b coupled to the separator tube port 430, external air 990 may be drawn into the dual-flow device 400a through the filtered air port 490, and conveyed into a separator tube 300a or 300b at the separator tube port 430 via the air needle 439. Pulling the plunger 660 of the transfer syringe 600 away from the end connector 610 thereof may then draw plasma 994 from within the separator tube 300a or 300b, and into the transfer syringe 660, via the plasma needle 431 and the end connector 610. In tum, more filtered air 994 may be drawn into the separator tube 300a or 300b to replace the plasma 994 that is so drawn out” (emphasis added); thus, equalization of pressures happens when both needles are penetrating the separator tube NOT equalized before the separator tube is coupled to the separator tube port as stated in amended claim 38 - “as the separator tube is coupled to the separator tube port, the air needle extends further toward a cap of the separator tube than the plasma needle to enable the air needle to penetrate the cap before the plasma needle is able to penetrate the cap to enable the interior of the separator tube to become coupled to the external air before becoming coupled to the syringe port, thereby enabling an equalization of air pressure within the interior of the separator tube with air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port”.
Additionally, [0072] of the original specification recites “Transferring the one or more portions of the plasma from within the at least one separator tube and into the at least one isolator may further include: coupling the transfer syringe to a syringe port of a transfer device; coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port of the transfer device, wherein the separator tube port comprises at least one hollow needle configured to simultaneously couple the separator tube port to the syringe port and to a filtered air port of the transfer device; 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 plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through an air filter at the filtered air port and into the separator tube through the transfer device.” (emphasis added); thus, the transfer of external air into the separator tube and withdrawal of plasma from the separator tube is simultaneous, NOT that the air goes in before the plasma is withdrawn.
Additionally, [0080] of the original specification recites “The kit may further include a transfer device, wherein: the transfer device may include a syringe port, a filtered air port comprising an air filter, and a separator tube port that comprises at least one hollow needle to configured to simultaneously couple the separator tube port to the syringe port and to the filtered air port; and while each separator tube of the at least one separator tube is coupled to the separator tube port, a plunger of the transfer syringe may be able to be operated to withdraw at least a portion of the plasma from the separator tube and into the transfer syringe through the transfer device, and to simultaneously cause air to be drawn through the air filter at the filtered air port and into the separator tube through the transfer device.” (emphasis added); thus, the transfer of external air into the separator tube and withdrawal of plasma from the separator tube is simultaneous, NOT that the air goes in before the plasma is withdrawn.
Hence, claims 58-59 clearly constitute new matter which must be removed from the claims to overcome this rejection.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 38-40, 43, 45-47, 49-50 and 58-59 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 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”).
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 1 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 the disclosures of Mijers and Sealfon.
Mijers teaches a fluid transfer device comprising a syringe port (6) which couples to a transfer syringe, i.e., a syringe port configured to be coupled to an end connector of the transfer syringe with a transfer needle of the transfer syringe disconnected from the end connector of the transfer syringe; a needle for withdrawing the fluid through the transfer device and into the syringe (8), i.e., a separator tube port of the transfer device, wherein the separator tube port comprises a hollow plasma needle that is separate and distinct from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to the syringe port of the transfer device; a venting needle connected to the outside air (9), i.e., the separator tube port comprises a hollow air needle that is separate and distinct from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to external air surrounding the transfer device; and a housing with a housing insert or inset, i.e., the separator tube port comprises a recess that is defined by the transfer device, that is configured to surround the plasma needle and the air needle to limit access to the plasma needle and the air needle, and that 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 (Abst.; Figs. 1-6; [0045-52]).
Mijers does not teach that the air needle is longer than the plasma needle; however, a person of ordinary skill in the art at the time of filing would have found it obvious in view of the disclosure of Sealfon.
Sealfon teaches transfer devices comprising 2 needles, one needle (104) connected to a syringe port (110) for withdrawing solution and a longer needle (102) connected to the external air (114), the arrangement of which Sealfon teaches is helpful for reducing foaming (Abst.; Fig. 1A). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to modify Mijers transfer device to comprise an air needle which is longer than the plasma needle to assist in reducing foaming.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to transfer the plasma from the separator to the isolator with the transfer device made obvious by Mijers in view of Sealfon because the transfer device made obvious by Mijers in view of Sealfon would provide protection from needle sticks, allow the release of pressure or vacuum from the interior of the separator tube to facilitate transfer of the plasma and reduce foaming of the liquid.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Hanna described above wherein the transfer of the plasma from the separator tube comprising a separator gel, to the isolator tube 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 wherein transferring the one or more portions of the plasma comprises: coupling the transfer syringe to a syringe port disposed on a first portion of an exterior of a transfer device to enable the transfer syringe and the transfer device to be used cooperatively to perform the transfer of the one or more portions of the plasma, wherein the syringe port is configured to be coupled to an end connector of the transfer syringe while a transfer needle of the transfer syringe is disconnected from the end connector of the transfer syringe; with the end connector of the transfer syringe remaining coupled to the syringe port of the transfer device, coupling each separator tube of the at least one separator tube, one at a time, to a separator tube port disposed on a second portion of the exterior of the transfer device, wherein: the separator tube port comprises a hollow plasma needle that is separate and distinct from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to the syringe port of the transfer device; the separator tube port comprises a hollow air needle that is separate and distinct from the plasma needle of the transfer device and from the transfer needle of the transfer syringe, and is configured to couple the separator tube port to external air surrounding the exterior of the transfer device; the separator tube port comprises a recess that is defined by the second portion of the exterior of the transfer device, that is configured to surround the hollow plasma needle and the air needle to limit access to the hollow plasma needle and the air needle, and that 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 hollow plasma needle, and to become coupled to the external air through the air needle, as the separator tube is inserted into the separator tube port; and as the separator tube is coupled to the separator tube port, the air needle extends further toward a cap of the separator tube than the plasma needle to enable the air needle to penetrate the cap before the plasma needle is able to penetrate the cap to enable the interior of the separator tube to become coupled to the external air before becoming coupled to the syringe port, thereby enabling an equalization of air pressure within the interior of the separator tube with air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port; while each separator tube of the at least one separator tube is coupled to the separator tube port, operating a plunger of the transfer syringe to withdraw at least one portion of the one or more portions of the plasma from the separator tube and into the transfer syringe through the plasma needle of the transfer device, and to draw a portion of the external air into the separator tube through the air needle of the transfer device; and following transfer of the one or more portions of the plasma from each separator tube of the at least one separator tube, disconnecting the end connector of the transfer syringe from the syringe port of the transfer device, connecting the transfer needle of the transfer syringe to the end connector of the transfer syringe, and using the transfer syringe to inject the one or more portions of the plasma into at least one isolator; subjecting the at least one isolator to a second centrifugal force in a second centrifuging stage for a second predetermined period of time to cause a combination of the second centrifugal force and the filter within each isolator of the at least one isolator to isolate the α2M molecules from other components of the plasma within the at least one isolator; retrieving at least the portion of the α2M molecules from within the at least one isolator, then injecting at least a portion of the α2M molecules into a musculoskeletal structure of a patient from which the whole blood was drawn; wherein the equalization of the air pressure within the interior of the separator tube with the air pressure of the external air prior to the interior of the separator tube becoming coupled to the syringe port comprises the removal of the vacuum prior to the interior of the separator tube becoming coupled to the syringe port; 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. 16-23) that the combination of references does not teach the transfer apparatus used in the claimed method. Applicant alleges that the transfer device made obvious by Mijers in view of Sealfon is not 1) separate and distinct from any component of a syringe; 2) is configured to couple multiple separator tubes (one at a time) to a single transfer syringe; 3) provides a syringe port to enable coupling to an end connector of the transfer syringe while the transfer needle of the transfer syringe is not coupled to that end connector; 4) provides a separator tube port within a recess that defines an opening to receive an end of each separator tube of the one or more separator tubes that is sealed with a cap; and 5) provides the separator tube port with a plasma needle positioned within the recess so as to be accessible only through the opening to prevent needle sticks therewith without needing to be fully covered, and to enable the coupling of each separator tube inserted into the separator tube port to the syringe port. Additionally, Applicant argues that the transfer device made obvious by Mijers in view of Sealfon is more complex than the instant transfer device.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant’s arguments are unpersuasive that the transfer device made obvious by Mijers in view of Sealfon does not meet each and every structural limitation in the claims; hence, the rejection is maintained.
Claims 38-43, 45-47, 49-51 and 58-59 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of Mijers, Sealfon, Esteron and Hanna et al., US 20150079194 (cite C, PTO-892, 4/30/2024; herein “Hanna#2”).
The discussion of Hanna, Mijers, Sealfon and Esteron regarding claims 38-40, 43, 45-47, 49-50 and 58-59 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 in view of Mijers, Sealfon, Esteron and Hanna#2, Applicant argues (p. 24) that Hanna#2 does not cure the deficiencies of Hanna, Mijers, Sealfon and Esteron. The alleged deficiencies of Hanna, Mijers, Sealfon and Esteron are discussed on pp. 18-19 above. Applicant is unpersuasive and the rejection is maintained.
Claims 38-43, 45-47, 49-51, 55 and 57-59 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of Mijers, Sealfon, Esteron, Hanna#2 and Mitchell, US 3300051 (cite D, PTO-892, 4/30/2024; herein “Mitchell”).
The discussion of Hanna, Mijers, Sealfon, Esteron and Hanna#2 regarding claims 38-43, 45-47, 49-51 and 58-59 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/PRP 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 a2M molecules from other components of the plasma within the at least one isolator comprises isolating the a2M 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 in view of Mijers, Sealfon, Esteron, Hanna#2 and Mitchell, Applicant argues (p. 24) that Mitchell does not cure the deficiencies of Hanna, Mijers, Sealfon, Esteron and Hanna#2. The alleged deficiencies of Hanna, Mijers, Sealfon and Esteron are discussed on pp. 18-19 above. Applicant is unpersuasive and the rejection is maintained.
Claims 38-43, 45-47, 49-51 and 55-58 are rejected under 35 U.S.C. 103 as being unpatentable over Hanna in view of Mijers, Sealfon, Esteron, Hanna#2, Mitchell and Aljefri, US 20200305781 (cite E, PTO-892, 4/30/2024; herein “Aljefri”).
The discussion of Hanna, Mijers, Sealfon, Esteron, Hanna#2 and Mitchell regarding claims 38-43, 45-47, 49-51, 55 and 57-58 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 in view of Mijers, Sealfon, Esteron, Hanna#2, Mitchell and Aljefri, Applicant argues (pp. 24-25) that Aljefri does not cure the deficiencies of Hanna, Mijers, Sealfon, Esteron, Hanna#2 and Mitchell. The alleged deficiencies of Hanna, Mijers, Sealfon and Esteron are discussed on pp. 18-19 above. Applicant is unpersuasive and the rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 39-41, 46, 49, 51 and 55-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 23-24 and 26-30 of copending Application No. 18/909731 (herein “’731”) in view of Hanna.
The method of claim 2 is essentially the same as instant claim 38 but for the a2M composition being administered by inhalation to treat a respiratory condition in ‘731 but injected into a musculoskeletal structure in the instan