Notice of Pre-AIA or AIA Status
The present application, filed on or after 22-May-2023, claims priority benefit under 35 U.S.C §119 of U.S. Provisional Application 63/344,258 filed on 20-May-2022 is being examined under the first inventor to file provisions of the AIA . The present application is related to Continuation-in-Part Application 18/517,066 filed on 22-November-2023.
Restriction Election
The response to the Restriction Requirement dated 21-July-2025 was received on 21-October-2025. Applicant elected without traverse, Group I, claims 1-15 and 25 drawn to a method of making a soluble Lox-1.
Claims 1, 2, 5, 6, 8, 9,and 10-25 were amended, Claim 3 was cancelled without prejudice or disclaimer, Claim 26 was added, and Claims 16-24 were amended to depend on method claims by the Applicant.
Claim Status
Claims 1-2 and 4-26 are pending and under examination. Claim 3 is canceled.
Drawings
The drawings filled on 17-August -2023 and 22-May-2023 are acknowledged and considered.
Information Disclosure Statement
An information disclosure statement has not been filed.
Claim Interpretation
I. Claims 1-2, 4-26, are directed to a method of making or producing autologous sLOX-1 (soluble LOX-1).
For the purposes of this examination, the term “configured to” in the claims is interpreted as reciting intended use/ result only, or functional capability; not a structural or process limitation and/or supported by structural/process features in the specification. Any claims reciting “configured to are interpreted as statements of intended function, unless followed by operative method steps enabling that function.
Claim Rejections - 35 USC§ 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.-The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2 and 4-26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding Claim 1, recites a method adding a coagulation enhancing material to a blood sample ex vivo, incubating the cultured blood clot, and comparing a concentration of sLOX-1 (soluble LOX-1) in a cultured clot serum to a concentration of sLOX-1 in fresh blood plasma or fresh blood serum to produce autologous sLOX-1. However, the claim fails to clearly set forth how the recited steps cooperate to achieve the outcome of producing autologous sLOX-1. Claim 1 lacks an introductory clause or preamble identifying the claimed subject matter; which makes the claim unclear as to the intended product being made or produced by the claimed method. Claim 1 recites “comparing a concertation” (e.g., comparing a concentration of sLox-1 (soluble Lox-1) in a cultured clot serum to a concentration of sLox-1 in: fresh blood plasma; or fresh blood serum of LOX-1 to a concentration of sLOX-1 in fresh blood plasma or serum); which does not specify how the comparison contributes to, or defines the production of autologous sLOX-1.
Claim 1 also recites “configured to produce autologous sLOX-1”, but fails to identify what structure or which active method steps achieve such configuration and does not specify how the configuration contributes to, or defines the production of autologous sLOX-1. Claim 1 is indefinite because one of ordinary skill in the art would be unable to determine, with reasonable certainty, how the claimed method steps perform together to produce the claimed outcome (e.g., production of autologous sLOX-1) in order to make and use the claimed invention. One of ordinary skill in the art would be unable to determine, with reasonable certainty, how the claimed method steps perform together to produce the claimed outcome (e.g., autologous sLOX-1), or what constitutes infringement.
Regarding Claims 2 and 4-26 are dependent claims (dependent on Claim 1) and do not add any additional clarification as to how the recited methods are configured to achieve the outcome of producing autologous sLOX-1. The claims do not introduce limitations that would provide reasonable certainty as to how the claim method contributes to, or defines the production of autologous sLOX-1 in order for someone of ordinary skill in the art to make and use the claimed invention. The dependent claims recite additional materials, concentration ranges, biological observations, comparisons. or intended screening outcomes; without adding method steps or clarifying how the claimed method is configured to produce autologous sLOX-1 (see Claim Interpretation).
Claim 23 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 23, which is dependent on Claim 1, recites the limitation “the device is used to screen for personalized responses to blood coagulation, inflammation-enhancing agents, drugs, proposed chemical treatments, or products derived from natural sources”; without a prior recitation of a “device” in the independent Claim 1. The device of Claim 23 is not included in, nor does it form part of the method defined in Claim 1. There is insufficient antecedent basis for this limitation in the instant Claim 23.
To overcome this rejection, the Applicant may amend the claims to provide antecedent basis for the recited material (device) to be consistent with the scope of the dependent claims from which Claim 23 depends.
Double Patenting (Obviousness Type)
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 Langi, 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/applyingonline/
eterminal-disclaimer.
Claims 1-2, 4-7, 9, 11-26 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 14, 16, 18-20 of copending U.S. Application No.18/517,066. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over US Application No.18/517,066. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US 18/517,066 teaches, a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25°C and less than 45°C for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedded in the device, wherein the method is configured to shed sLox-1 more than fresh blood (Claim 1); wherein an additional enhancing material comprising a lipopolysaccharide (LPS) or phorbol myristate acetate and configured to modulate sLox-1 is added to the cultured blood clot (Claim 2); wherein the cultured blood clot is configured to produce one or more interleukins and/or cytokines (Claim 3); wherein addition of the coagulation enhancing material in the device spikes shedding of sLox-1 into the device by about 20% to 60% more compared to a cultured blood clot free of the coagulation enhancing material (Claim 4); wherein the method is configured to shed 0.2 ng to 50ng of the sLox-1 per ml of the blood sample (Claim 5); wherein the method is configured to produce an autologous sLox-1(Claim 6); the device is incubated for a time-period ranging from at least 2 hours to 18 hours (Claim 7); wherein the device comprises a thrombus device (Claim 8); wherein the method is configured to detect a drug response in whole blood (Claim 14); wherein one or more interleukins and/or cytokines comprise IL-8, IL- 6, TNF or a combination thereof (Claim 16); wherein the cultured blood clot comprises about 1.5 to 5 times more Lox-1+/CD15+ containing neutrophils than the fresh blood clot (Claim 18); wherein the method is configured to estimate an amount of active alpha- 1 antitrypsin in a sample to detect a disease in a subject (Claim 19); wherein the temperature is in a range of about 30°C to about 42°C (Claim 20);
Regarding Claim 1, US 18/517,066 recites a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedding in the device, wherein the method is configured to shed sLox-1 more than fresh blood (Claim 1). US 18/517,066 recites wherein the method is configured to produce an autologous sLox-1(Claim 6), and further recites wherein the cultured blood clot comprises about 1.5 to 5 times more Lox-1+/CD15+ containing neutrophils than the fresh blood clot (Claim 18).
Although US 18/517,066 does not explicitly teach comparing the concentration of sLox-1 in a cultured clot serum to a concentration of sLox-1 in fresh blood plasma or fresh blood serum; US 18/517,066 teaches “the method is configured to shed sLox-1 more than fresh blood; and the “cultured blood clot comprises about 1.5 to 5 times more Lox-1+/CD15+ containing neutrophils than the fresh blood clot. A person of ordinary skill in the art would have been motivated to include a comparison step to verify and quantify the stated increase of more sLox-1 in the cultured blood clot of US 18/517,066 with a reasonable expectation of success because adding the comparison step would have verified the method of US 18/517,066 producing more sLox-1 than the fresh blood clot. Therefore, it would have been obvious to include comparing sLox-1 concentrations between the cultured clot serum and fresh blood, with a reasonable expectation of success in obtaining measurable differences with the motivation to optimize the method of US 18/517,066 to verify more sLox-1 production in the cultured blood clot.
Regarding Claim 2, US 18/517,066 recites a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; whereas an additional enhancing material comprising a lipopolysaccharide (LPS) or phorbol myristate acetate and configured to modulate sLox-1 is added to the cultured blood clot. (Claim 2).
Regarding Claim 4, US 18/517,066 recites a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; wherein addition of the coagulation enhancing material in the device spikes shedding of sLox-1 into the device by about 20% to 60% more compared to a cultured blood clot free of the coagulation enhancing material (Claim 3).
Regarding Claim 5, 12, and 14-15, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; wherein one or more interleukins and/or cytokines comprise IL-8, IL-6, TNF or a combination thereof (Claim 16).
Regarding Claim 6, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; wherein addition of the coagulation enhancing material in the device spikes shedding of sLox-1 into the device by about 20% to 60% more compared to a cultured blood clot free of the coagulation enhancing material (Claim 4).
Regarding Claim 7 and 13, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; wherein the method is configured to shed 0.2 ng to 50 ng of the sLox-1 per ml of the blood sample (Claim 5).
Regarding Claim 9, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; the device is incubated for a time-period ranging from at least 2 hours to 18 hours (Claim 7).
Regarding Claim 11, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shredded in the device, wherein the method is configured to shed sLox-1 more than fresh blood; wherein the device comprises a thrombus device (Claim 8).
Regarding Claim 16, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedding in the device, wherein the method is configured to shed sLox-1 more than fresh blood (Claim 1); wherein the device comprises a thrombus device (Claim 8); wherein the method is configured to detect a drug response in whole blood (Claim 14); wherein the method is configured to estimate an amount of active alpha- 1 antitrypsin in a sample to detect a disease in a subject (Claim 19); wherein the temperature is in a range of about 30°C to about 42°C (Claim 20);
Although US 18/517,066 does not explicitly teach the device called a “vacutainer tube and a heater”; and configuring the device to screen agents that promote or inhibit one or more cell biologically processes (e.g., cell apoptosis, scramblase activity, ADAM17 activity, ADAM10 activity, alpha secretase activity, sLox-1 sheddase activity, and tumor necrosis factor activation); US 18/517,066 does teach a thrombus device comprising incubation at 25° C. and less than 45° C. A person of ordinary skill in the art would have known that thrombus device with incubation functions in blood collection and experimentation, as a vacutainer and a heater. The device of US 18/517,066 is used to incubate blood samples and measure resulting biomarker production (e.g., sLox-1).
Although US 18/517,066 does not explicitly teach the device configured to screen agents; the device of US 18/517,066 is configured to detect a drug response, and configured to detect a disease. Therefore the device of US 18/517,066 is reasonably capable of performing the claimed screening functions of maintaining temperature and configured to screen agents. =
It would have been obvious to a person of ordinary skill in the art to utilize the device and method of US 18/517,066 with the motivation to maintain an incubation temperature of incubation at 25° C. and less than 45° C, and configured to screen agents detected in the culture blood clot (e.g., cell apoptosis, scramblase activity, ADAM17 activity, ADAM10 activity, alpha secretase activity, sLox-1 sheddase activity, and tumor necrosis factor activation) with a reasonable expectation of success.
Regarding Claim 17, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedding in the device, wherein the method is configured to shed sLox-1 more than fresh blood (Claim 1); wherein the device comprises a thrombus device (Claim 8); wherein the method is configured to detect a drug response in whole blood (Claim 14); wherein the method is configured to estimate an amount of active alpha- 1 antitrypsin in a sample to detect a disease in a subject (Claim 19); wherein the temperature is in a range of about 30°C to about 42°C (Claim 20).
Although US 18/517,066 does not explicitly teach configuring the device to screen a drug, antibody, nanoparticle, nucleic acid, RNA-based nanoparticle, metal, vitamin, biomaterial, or nutraceutical/dietary supplement causing an increase or decrease in cultured clot serum sLox-1 relative to untreated cultured clot serum sLox-1, without inducing cell necrosis; the device of US 18/517,066 is configured to detect a drug response, and configured to detect a disease. The device configuration is interpreted as functional language describing the intended use or intended capability of the device, and not a structural limitation (see Claim Interpretation above). Therefore the device of US 18/517,066 is reasonably capable of performing the claimed screening functions.
It would have been obvious to a person of ordinary skill in the art to utilize the device and method of US 18/517,066, wherein the device is configured to detect a drug response, and configured to detect a disease; to also be configured to screen a drug, antibody, nanoparticle, nucleic acid, RNA-based nanoparticle, metal, vitamin, biomaterial, or nutraceutical/dietary supplement causing an increase or decrease in cultured clot serum sLox-1 relative to untreated cultured clot serum sLox-1, without inducing cell necrosis; with a reasonable expectation of success of screening for agents because the device and method of US 18/517,066 is configured (e.g., intended use/ result only, or functional capability) to detect agents (identifying agents), hence one of ordinary skill in the art would be motivated to use the device configured to screen agents.
Regarding Claim 18, the instant Claim 18 further recites, “the drug is a chemotherapeutic agent intended to induce apoptosis”, which merely states the name of the drug configured by the device of Claim 17, and does not require use of the drug in the method step. Therefore, dependent Claim 18 is rejected with the claim in which it depends, Claim 17.
Regarding Claims 19-22 and 24, Configuration is interpreted as functional language describing the intended use or intended capability of the device, and not a structural limitation (see Claim Interpretation above). Instant Claim 19 recites,” the drug is configured to decrease ADAM17 activity and TNF activation”; instant Claim 20 recites, “the drug is configured to suppress TNF expression or activity”; instant Claim 21 recites, “the drug comprises a serine- threonine phosphatase inhibitor”; instant Claim 22 recites, “the drug comprises beta glycerol phosphate”; and instant Claim 24 recites, “the drug is configured to alter polymorphonuclear myeloid derived suppressor cell activity or viability. Claims 19-22 and 24 merely states the drug configuration functions, and the instant claims do not require use of the drug in the method step. Therefore, the instant Claims are rejected with the claim in which they depend, Claim 17.
Regarding Claim 23, instant Claim 23 further recites, “the device is used to screen for personalized responses to blood coagulation, inflammation-enhancing agents, drugs, proposed chemical treatments, or products derived from natural sources”, which merely states how to use the device or states how the device is used, and does not require use of the device in the method step. Therefore, dependent Claim 23 is rejected with the claim in which it depends, Claim 1.
Regarding Claim 25, US 18/517,066 teaches a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedding in the device, wherein the method is configured to shed sLox-1 more than fresh blood (Claim 1).
Although US 18/517,066 does not explicitly teach the blood sample is free of an anticoagulant factor, the method of US 18/517,066 requires formation of a blood clot to produce and shed sLox-1. The presence of anticoagulants would inhibit or prevent clot formation. A person of ordinary skill in the art would have understood that the presence of anticoagulants inhibits or prevents clot formation, and in order for clot-formation to occur, the blood sample must be free of anticoagulant factors; or not contain anticoagulants in an amount sufficient to prevent coagulation. Accordingly, the absence of anticoagulants represents an inherent and necessary condition of the method of US 18/517,066, and would have been obvious to a person of ordinary skill in the art with a reasonable expectation of success producing sLox-1 from a blood sample.
Regarding Claim 26, US 18/517,066 recites a method of generating, ex vivo production of soluble Lox-1 (sLox-1), comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedding in the device, wherein the method is configured to shed sLox-1 more than fresh blood (Claim 1).
Although US 18/517,066 does not explicitly teach fresh blood plasma is anticoagulated plasma, a person of ordinary skill in the art would have understood that blood plasma is obtained in the absence of coagulation. Thus, a person of ordinary skill in the art would have found it obvious to use fresh blood plasma (i.e., anticoagulated plasma) as the comparison sample for biomarker analysis. Accordingly, it would have been obvious to a person ordinary skill in the art to use the comparison sample (i.e., fresh blood plasma that is anticoagulated plasma) of the method of US 18/517,066 to compare amounts of sLox-1 produced from a cultured blood clot would have been obvious to a person of ordinary skill in the art with a reasonable expectation of success to be motivated to use fresh blood plasma as an optimal comparison sample to verify the production of sLox-1 during experimentation.
Claim(s) 8 and 10 are provisionally rejected on the grounds of nonstatutory double patenting over US18/517,066 as applied above to Claims 1-2, 4-7, 9, 11-15, and 25-26, in further view of Wang et.al., 2009 (hereafter, “Wang”, see form 892).
US 18/517,066 recites a method of generating, ex vivo production of sLox-1, comprising: introducing a sample containing blood into a device; adding a coagulation enhancing material in the sample to form a cultured blood clot; incubating the cultured blood clot in the device at a temperature greater than 25° C. and less than 45° C. for at least 2 hours to allow production of Lox-1 from neutrophils of blood and to shed the sLox-1 outside the cultured blood clot; and collecting sLox-1 shedding in the device, wherein the method is configured to shed sLox-1 more than fresh blood; wherein addition of the coagulation enhancing material in the device spikes shedding of sLox-1 into the device by about 20% to 60% more compared to a cultured blood clot free of the coagulation enhancing material; and wherein the method is configured to shed sLox-1 more than fresh blood; wherein one or more interleukins and/or cytokines comprise IL-8, IL-6, TNF or a combination thereof (previously discussed above).
US18/517,066 does not teach RNA sequencing of a cultured blood clot.
Wang teaches RNA sequencing (RNA-seq) as a technique for analyzing gene expression in biological samples, including cells and tissue. Wang recites the use of RNA sequencing as a quantitative method to determine RNA expression levels more accurately, and to determine the absolute quantity of every molecule in a cell population; and directly compare results between experiments (Pg. 63, Col. 1, Para. 1).
A person of ordinary skill in the art would have been motivated to apply RNA sequencing to the cultured blood clot of US18/517,066 in order to determine the molecular and cellular composition of the cultured blood clot and to determine the quantity of biomarker production of sLox-1 in the cultured blood clot. Applying a known gene expression analysis technique to a known biological system represents routine experimentation. Therefore, it would have been obvious to modify the method of US18/517,066 to include RNA sequencing, with a reasonable expectation of success of quantifying the number of sLox-1 biomarkers and other molecules in the cultured clot.
It would have been obvious to one of ordinary skill in the art at the time of the invention to reasonably combine the methods of US 18/517,066 with the teachings of Wang with a reasonable expectation of success because combined, the teachings create optimized methods for the intended purpose of producing sLox-1, including RNA sequencing of the cultured blood clot.
Additionally, the scope of the claims of US 18/517,066 significantly overlap with the instant claims, combined with the teachings of Wang. Thus, one of ordinary skill in the art would have been motivated to combine the method teachings of US 18/517,066 with Wang because all elements of the teachings were known in the art as standard experimentation methods that can be used to the production of sLox-1; therefore, combining them would have yielded predictable results combining known elements performing functions that are obvious over 18/517,066, in further view of Wang.
Regarding Claim 8, US 18/517,066 recites a method of generating ex vivo production of soluble Lox-1 (previously discussed); and Wang teaches RNA sequencing (RNA-seq) as a technique for analyzing gene expression in biological samples, including cells and tissue.
Regarding Claim 10, US 18/517,066 recites a method of generating SLOX-1 (previously discussed); and Wang teaches RNA sequencing (RNA-seq) as a technique for analyzing gene expression in biological samples, including cells and tissue (previously discussed). The instant Claim 8 recites, wherein the sLox-1 produced from the cultured clot serum is a personalized anti-coagulant agent. The recitation that the sLox-1 is a personalized anti-coagulant agent constitutes as intended use or functional description of the product produced by the methods and is not a structural or method step limitation. Claim 10 is rejected along with the claim in which it depends (i.e., Claim 8) because instant Claim 10 does not further limit the scope the claim from which it depends.
Claim Rejections - 35 USC§ 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 non-obviousness.
Claim(s) 1, 4-7, 9, 12-15, 23, and 25-26 are rejected under 35 U.S.C 103 as being unpatentable over US 2023/0280359 A1 (2022; hereafter “Patzke”, see Form 892), in further view of Murase et al., 2000 (hereafter, “Murase”, see Form 892).
Patzke teaches test methods for establishing an individual’s blood coagulation system status and providing information of the functionality of the blood coagulation cascade (Abstract; Paragraph [0009]). Patzke teaches a test method wherein a whole blood sample is introduced to a coagulation activator into the sample such that a cultured blood clot is formed, the cultured blood clot is allowed to incubate at 37°C, and then the amount of a secreted protein is quantifiably measured and compared to a reference value of a blood sample that does not comprise an added coagulation activator (Paragraphs [0007], [0010]-[0017], [0021], [0030], [0035]-[0036], [0053]-[0056], [0083], [0102], [0164],[0166]). Patzke further discloses that the coagulation activator may be a substance that activates leukocytes, for example proinflammatory cytokines (TNF-α, IL-8), which induce cell death in neutrophils (“NETosis”) and lead to the formation of neutrophil extracellular traps, which have a strongly prothrombotic effect (Paragraph [0027]).
Patzke does not teach incubating the cultured blood clot at least 2 hours to 18 hours. Patzke teaches quantifiably measuring and comparing the amount of secreted proteins from the blood clot and the blood free of the coagulation activator; however Patzke does not specifically teach the secreted proteins as sLox-1 (i.e., a type II membrane protein [Murase, Abstract]). Therefore, Patzke does not specifically teach comparing a concentration of sLox-1 in cultured clot serum to a concentration of sLox-1 in fresh blood plasma or fresh blood serum; and the method configured to produce autologous sLox-1.
Murase teaches methods of extracting soluble LOX-1 (i.e., lectin-like oxidized LDL receptor-1, a type II membrane protein) from cultured cells, “soluble forms of LOX-1 are present in conditioned media of cultured bovine aortic endothelial cells [BAECs] and CHO-K1 cells [Abstract]). Soluble receptors (e.g., sLox-1) are present in circulating blood of humans, and plasma concentrations of soluble receptors are correlated with the levels of receptor expression on the cell surface; and measuring plasma levels of soluble LOX-1 might reflect disease status (pg. 719, col. 2, para.4). Murase teaches “elevated levels of soluble forms of membrane proteins in circulating blood in humans may reflect increased expression of membrane proteins and disease activities, and “Lox-1 may release soluble forms” (Pg. 715, Col 2, Para. 2-3). Murase teaches “both expression of membrane-anchored LOX-1 and production of soluble LOX-1 induced by TNF- α” (pg. 716, col. 2, Results, para.1). Murase teaches, recognition of LOX-1 cleavage sites by the putative converting enzyme may depend on the protein conformation; conformation- or position-dependent recognition of membrane proteins by proteases has been implicated in the shedding of IL-6 receptor and L-selectin; and 2 different proteases may specifically shed LOX-1 at 2 different sites, both of which are sensitive to PMSF (pg. 719, col. 2, para. 2). Murase teaches, elevated levels of soluble forms of membrane proteins in circulating blood in humans may reflect increased expression of membrane proteins and disease activities (pg.715, col. 2, para. 1). Murase teaches “soluble LOX-1 detectable as early as 8 hours after the treatment in increased for 24 hours” (pg. 716, col. 2, Results, para.1). Murase teaches the incubation (temperature control) of cultured cells (“incubated at room temperature for 15 to 30 minutes; incubated at 37°C for 24 hours [pg. 716, col. 1, Cell-Surface Biotinylation and Immunoprecipitation, para.1]). With regard to the regulation of expression, LOX-1 can be upregulated by inflammatory stimuli, such as tumor necrosis factor (TNF)-a and phorbol ester, 6 and by a mechanical stimulus, fluid shear stress,7 in cultured bovine aortic endothelial cells (BAECs)” [pg. 715, col.1, Introduction, para.1].
It would have been obvious to one of ordinary skill in the art at the time of the invention to reasonably combine the methods of Patzke, with the teachings of Murase because Patzke provides a structured system for handling, culturing, analyzing, and quantifying whole blood samples to form cultured blood clots, and secreting proteins found in blood; and Murase teaches sLox-1 is released into circulating blood and that sLox-1 levels correlate with membrane LOX-1 expression and disease activity, wherein identifying sLox-1 as a clinically relevant type II membrane protein of interest for disease detection. Murase further teaches sLox-1 levels and expression and can be detected following incubation of stimulated cells (e.g., 37°C for 24 hours ).
A person of ordinary skill in the art would have been motivated to combine the teachings of Patzke and Murase with a reasonable expectation of success because Patzke teaches collecting and maintaining whole blood to form a cultured blood clot; wherein providing a suitable system for evaluating blood-derived factors; wherein Murase teaches conditions for extracting sLox-1 for detecting disease activity. It would have been obvious to apply Murase's known conditions for extracting sLox-1 to Patzke’s methods for handling, culturing, analyzing, and quantifying whole blood and producing cultured blood clots for secreting proteins and other biomarkers; which a reasonable expectation of success because combined yield an obvious method of collecting and maintaining whole blood to form a cultured blood clot; wherein extracting/ secreting types of proteins in soluble form (e.g., sLox-1) as biomarkers for detecting disease activity. Therefore, Patzke’s methods for secreting proteins from a cultured blood clot provides a suitable environment for producing Murase’s detectable sLox-1. The combination uses established techniques for blood handling and incubating blood samples to obtain the predictable result of producing and measuring protein biomarkers, such as sLox-1 from a cultured blood samples.
Regarding Claim 1: Although Murase and Patzke does not explicitly teach comparing concentrations of sLox-1, Patzke does teach comparing the amount of secreted proteins and quantifiably measuring and comparing to a referenced value of a blood sample that does not comprise any added activators (i.e., uncultured whole blood). A person of ordinary skill in the art would have been motivated to include a comparison step of comparing the amount of sLox-1, along with comparing other proteins to verify and quantify the stated increase of more sLox-1 in the cultured blood clot of Murase. Therefore, it would have been obvious to include comparison step of Patzke to include the comparison of sLox-1 concentrations between the cultured clot serum and fresh blood, with a reasonable expectation of success in obtaining measurable differences in order to optimize the method of Murase.
Regarding Claims 6-7, and 13: Additionally, the amount of sLox-1 shed from the cultured blood clot is interpreted as an intended result. It would have been obvious to a person of ordinary skill in the art to adjust stimulation conditions, including configuring or adjusting the coagulation enhancing material of Patzke and Murase in order to increase the release of sLox-1 from the cultured blood clot. Optimization of such conditions to increase sLox-1 shedding by amounts (i.e., 20% to 60%) represents routine optimization for improving the detectable release of the sLox-1. An optimum or workable range of a result-effective variable through routine experimentation is considered obvious (see In re Aller, 22 F.2d 454;MPEP 2144.05). Murase teaches producing detectable levels of sLox-1 following incubation and stimulation of the cultured cells. The specific quantitative concentration of sLox-1 produced in the sample would depend on routine experimental variables (i.e., incubation time, cell activation time, and clot-forming parameters). Selecting a detectable concentration range (i.e., 0.5ng to 50ng) would represent routine optimization of known experimental conditions in order to obtain measurable levels of sLox-1. Accordingly, the recited percentages of shedding amounts and concentration ranges represent optimization of result-effective variables associated with sLox-1 production and detection; which would have been obvious to a person of ordinary skill in the art.
Regarding Claims 4-5, 12, and 14-15: Patzke and Murase teach one or more interleukins, disclosing IL-6 and IL-8. Patzke teaches the coagulation activator may be a substance that activates leukocytes, for example proinflammatory cytokines (TNF-α, IL-8). Murase teaches the recognition of LOX-1 cleavage by proteases has been implicated in the shedding of IL-6 receptors. A person of ordinary skill in the art would have understood that exposure of blood-derived cells to coagulation activators results in activation of immune pathways and the production of inflammatory signaling molecules. Accordingly, when the cultured blood clot of Patzke is stimulated by coagulation activators, the cultured blood cells within the clot would predictably produce cytokines, including one or more interleukins (i.e., IL-6, IL-8, IL-12, IL-36, IL-1A, IL-1B, and/or IL-18). Therefore, the limitation that the cultured blood clot is configured to produce one or more interleukins does not further limit the claim because interleukin production is an inherent and predictable biological response of activated blood-derived immune cells within the cultured blood clot. Additionally, one of ordinary skill in the art would have been motivated to apply the structured system for quantifying secreted proteins to the produced interleukins with in order to quantify the concentration of interleukins with a reasonably expectation of success determining of concentrations of interleukins; including IL-6 and Il-8. Thus, it would have been obvious to a person of ordinary skill in the art to stimulate the cultured cells of Patzke and Murase using the coagulation activators of Patzke, with a reasonable expectation of success resulting in the production of one or more interleukins and quantifying the concentrations of the interleukins.
Regarding Claim 9, Patzke and Murase teach a method of handling, culturing, and quantifying cultured cells; including culturing whole blood to form a cultured blood clot and producing/shedding/secreting proteins from the sample (e.g., sLox-1); producing sLox-1 under standard clot-forming conditions (i.e., detecting sLox-1 as early as 8 hours after the treatment in increased for 24 hours, incubation [temperature control] of blood cells to form cultured blood cells, and incubation of cultured blood cells at room temperature for 15 to 30 minutes, and incubated at 37°C for 24 hours.
Regarding Claim 23, instant Claim 23 further recites, “the device is used to screen for personalized responses to blood coagulation, inflammation-enhancing agents, drugs, proposed chemical treatments, or products derived from natural sources”, which merely states how to use the device or states how the device is used, and does not require use of the device in the method step. Therefore, dependent Claim 23 is rejected with the claim in which it depends, Claim 1.
Regarding Claim 25: Patzke teaches forming and culturing a blood clot; wherein the blood sample used must be free of anticoagulant factors; as the presence of anticoagulant agents would prevent clot formation. Therefore, the limitation that the blood sample is free of an anti-coagulant factor is inherently satisfied by the clot-forming conditions taught by Patzke. A person of ordinary skill in the art would have known that the limitation (i.e., the blood sample being free from anticoagulant factors) is necessarily inherent in order for the blood sample to clot and form a cultured blood clot or cultured blood serum (see MPEP 2112; In re Best, 562 F.2d 1252 (CCPA 1977)).
Regarding Claim 26: Although Murase and Patzke do not explicitly teach fresh blood plasma is anticoagulated plasma, a person of ordinary skill in the art would have understood that blood plasma is obtained in the absence of coagulation. Thus, a person of ordinary skill in the art would have found it obvious to use the fresh whole blood of Patzke (i.e., anticoagulated plasma) as the comparison sample for biomarker analysis. Accordingly, it would have been obvious to a person ordinary skill in the art to use the comparison sample (i.e., fresh whole blood plasma that is anticoagulated plasma) of Patzke to compare amounts of sLox-1 produced from a cultured blood clot using the combined methods of Patzke and Murase for producing sLox-1, with a reasonable expectation of success for comparing amounts of sLox-1 from fresh blood plasma or serum.
Claim(s) 2 is rejected under 35 U.S.C 103 as being unpatentable over Patzke and Murase as applied to Claims 1, 4-7, 9, 12-15, 23, and 25-26 above, in further view of Lehrer et.al., 2021 (hereafter “Lehrer”; see Form 892).
Patzke and Murase render obvious a method of handling, culturing, and quantifying cultured cells; including culturing whole blood to form a cultured blood clot and producing/shedding/secreting protein biomarkers from a sample (e.g., sLox-1); producing sLox-1 under standard clot-forming conditions (i.e., detecting sLox-1 as early as 8 hours after the treatment in increased for 24 hours, incubation [temperature control] of blood cells to form cultured blood cells, and incubation of cultured blood cells at room temperature for 15 to 30 minutes, and incubated at 37°C for 24 hours [previously discussed]).
Murase and Patzke do not specifically teach adding an additional enhancing material comprising a lipopolysaccharide (LPS) or phorbol myristate acetate.
Lehrer teaches “Lipopolysaccharides or LPS are normally present in the blood at very low levels. In certain infections, LPS levels increase substantially, causing sepsis. LPS can also enter the blood during leaky gut or with certain types of fat (Paragraph 1 under ”What are LPS?” and subtitle: “Definition”).
Thus, Lehrer teaches that LPS is a naturally occurring inflammatory stimulus present in the blood and known to increase during inflammatory conditions.
A person with ordinary skill in the art would have understood that LPS functions as an inflammatory activator capable of stimulating cellular responses in blood-derived cells. Similarly, Murase teaches stimulating cultured blood cells using phorbol esters to induce cellular activation and promote production of sLox-1. Therefore, it would have been obvious to a person of ordinary skill in the art to add LPS to the cultured blood clot of Patzke as an alternative inflammatory stimulus in order to stimulate cellular activation and promote the production of sLox-1. Substituting one known cellular activation agent for another known inflammatory stimulus represents the use of a known technique to stimulate a biological response in cultured blood cells and would have a reasonable expectation of success in the activation of blood cells and production of sLox-1 as the result. Such substitution of one known activator for another known activator constitutes the predictable use of prior art elements according to their established functions.
Claim(s) 8 and 10 are rejected under 35 U.S.C 103 as being unpatentable over Patzke and Murase as applied to Claims 1, 4-7, 9, 12-15, 2, and 25-26 above, in further view of Wang et.al., 2009 (hereafter, “Wang”, see form 892).
Patzke and Murase render obvious a method of handling, culturing, and quantifying cultured cells; including culturing whole blood to form a cultured blood clot and producing/shedding/secreting protein biomarkers from a sample (e.g., sLox-1) sLox-1; producing sLox-1 under standard clot-forming conditions (i.e., detecting sLox-1 as early as 8 hours after the treatment in increased for 24 hours, incubation [temperature control] of blood cells to form cultured blood cells, and incubation of cultured blood cells at room temperature for 15 to 30 minutes, and incubated at 37°C for 24 hours [previously discussed]).
Patzke and Murase do not specifically teach RNA sequencing and sLox-1 as personalized anti-coagulant agent.
Wang teaches RNA sequencing (RNA-seq) as a technique for analyzing gene expression in biological samples, including cells and tissue. Wang recites the use of RNA sequencing as a quantitative method to determine RNA expression levels more accurately, and to determine the absolute quantity of every molecule in a cell population; and directly compare results between experiments (Pg. 63, Col. 1, Para. 1).
A person of ordinary skill in the art would have been motivated to apply RNA sequencing of Wang to the cultured blood clot of Patzke using the combined methods of Patzke and Murase, producing sLox-1 in order to determine the molecular and cellular composition of the cultured blood clot; and to determine the quantity of biomarker production of sLox-1 in the cultured blood clot. Applying a known gene expression analysis technique to a known biological system represents routine experimentation. Therefore, it would have been obvious to modify the method of Patzke and Murase to include RNA sequencing, with a reasonable expectation of success of quantifying the number of sLox-1 biomarkers and other molecules in the cultured clot.
It would have been obvious to one of ordinary skill in the art at the time of the invention to be motivated to combine the methods Patzke and Murase with the teachings of Wang with a reasonable expectation of success because combined, the teachings create optimized methods for the intended purpose of producing sLox-1, including RNA sequencing of the cultured blood clot.
Thus, one of ordinary skill in the art would have been motivated to combine the method teachings of Patzke and Murase, with Wang because all elements of the teachings were known in the art as standard experimentation methods that can be used for the production of sLox-1 and combining all elements would yield optimized standard experimentation methods for the production of sLox-1; therefore, combining them would have yielded predictable results combining known elements performing functions that are obvious over Patzke and Murase, in further view of Wang.
Regarding Claims 8 and 10, Patzke and Murase teach a method of generating SLOX-1 (previously discussed); and Wang teaches RNA sequencing (RNA-seq) as a technique for analyzing gene expression in biological samples, including cells and tissue (previously discussed). The instant Claim 8 recites, wherein the sLox-1 produced from the cultured clot serum is a personalized anti-coagulant agent. The recitation that the sLox-1 is a personalized anti-coagulant agent constitutes as intended use or functional description of the product produced by the methods and is not a structural or method step limitation. Claim 10 is rejected along with the claim in which it depends (i.e., Claim 8) because instant Claim 10 does not further limit the scope the claim from which it depends.
Claim(s) 11, 16-22, and 24 are rejected under 35 U.S.C 103 as being unpatentable over Patzke and Murase as applied to Claims 1, 4-7, 9, 12-15, 23, and 25-26 above, in further view of Pennings et al., 2014; and hereafter “Pennings” (see Form 892).
Patzke and Murase render obvious a method of handling, culturing, and quantifying cultured cells; including culturing whole blood to form a cultured blood clot and producing/shedding/secreting protein biomarkers from a sample (e.g., sLox-1) sLox-1; producing sLox-1 under standard clot-forming conditions (i.e., detecting sLox-1 as early as 8 hours after the treatment in increased for 24 hours, incubation [temperature control] of blood cells to form cultured blood cells, and incubation of cultured blood cells at room temperature for 15 to 30 minutes, and incubated at 37°C for 24 hours [previously discussed]).
Murase and Patzke do not specifically teach adding the blood sample into a device comprising a thrombus device; wherein the device comprises a vacutainer tube and a heater; and the device is configured to screen agents.
Pennings teaches using a device; a “novel thrombus aspiration catheter, the Thrombuster II” introduced into clinical practice, “capable of local blood collection” within the coronary tree (pg. 326, col. 1, Abstract). Pennings teachings “aliquot of sampled blood transferred into CTAD blood collection tubes (pg. 327, col. 1, Methods, para. 2).
It would have been obvious to one of ordinary skill in the art at the time of the invention to be motivated to combine the methods of Patzke and Murase with the teachings of Pennings because Murase teaches that sLox-1 is released into circulating blood and its levels correlate with membrane LOX-1 expression and disease activity; wherein identifying sLox-1 as an important membrane protein of interest for disease detection. Also, Murase teaches extracting sLox-1 via standard incubation. Additionally, Patzke provides a system for collecting and maintaining whole blood to form a cultured blood clot, and Pennings teaches using a device (i.e. a thrombus device; a vacutainer tube), which can be configured (i.e., an intended function, see above claim interpretation section) to screen agents and biomarkers (e.g., plasma sensitive to a target drug; or an agent selected from one or more of the following: cell apoptosis, scramblase activity, flippase activity, ADAM17 activity, ADAM10 activity, alpha secretase activity, sLox-1 sheddase activity and tumor necrosis factor activation). Hence, Patzke requires collection and handling of whole blood in a device, while Murase teaches that sLox-1 is produced and released under controlled incubation conditions; wherein the blood collection device (e.g., a vacutainer or thrombus device) of Pennings is a predictable and suitable element for extracting measurable sLox-1 and other biomarkers in a controlled environment.
It would have been obvious to apply Murase’s conditions for extracting sLox-1 within Patzke’s method of collecting and maintaining whole blood to form a cultured blood clot; wherein extracting/ secreting types of protein biomarkers in soluble form (e.g., sLox-1) for detecting disease activity, using the suitable device of Pennings (a vacutainer or thrombus device capable of detecting biomarkers and other agents.
Regarding Claims 11 and 16, although Pennings does not explicitly teach the device called a “vacutainer tube and a heater”; and configuring the device to screen agents that promote or inhibit one or more cell biologically processes (e.g., cell apoptosis, scramblase activity, ADAM17 activity, ADAM10 activity, alpha secretase activity, sLox-1 sheddase activity, and tumor necrosis factor activation), Pennings does teach a thrombus device comprising incubation at 25° C. and less than 45° C. A person of ordinary skill in the art would have known that thrombus device with incubation functions in blood collection and experimentation, as a vacutainer and a heater. The device of Pennings is used to incubate blood samples and measure resulting biomarker production (e.g., sLox-1).
Although Pennings does not explicitly teach the device configured to screen agents; device configuration is interpreted as functional language describing the intended use or intended capability of the device, and not a structural limitation. Therefore the device of Pennings is reasonably capable of performing the claimed screening functions of maintaining temperature and configured to screen agents.
It would have been obvious to a person of ordinary skill in the art to utilize the device of Pennings; combined with the methods of Patzke and Murase to maintain an incubation temperature of incubation at 25° C. and less than 45° C, and configured to screen agents detected in the culture blood clot (e.g., cell apoptosis, scramblase activity, ADAM17 activity, ADAM10 activity, alpha secretase activity, sLox-1 sheddase activity, and tumor necrosis factor activation) with a reasonable expectation of success.
It would have been prima facie obvious to have modified the teachings of Patzke and Murase to include the teachings of Pennings to produce autologous sLox-1 using optimized method steps (e.g., optimized blood collection device). The instant claims are directed to a combination of known elements performing established functions that are obvious over Patzke and Murase, in view of Pennings (As described MPEP 2143, Section A. Combining Prior Art Elements According to Known Methods To Yield Predictable Results).
Regarding Claim 17, although Pennings does not explicitly teach configuring the device to screen a drug (i.e., chemotherapeutic agent), antibody, nanoparticle, nucleic acid, RNA-based nanoparticle, metal, vitamin, biomaterial, or nutraceutical/dietary supplement causing an increase or decrease in cultured clot serum sLox-1 relative to untreated cultured clot serum sLox-1, without inducing cell necrosis; the device configuration is interpreted as functional language describing the intended use or intended capability of the device, and not a structural limitation (see Claim Interpretation above). Therefore the device of Pennings is reasonably capable of performing the configuration to screen agents.
It would have been obvious to a person of ordinary skill in the art to be motivated to utilize the device and method of Pennings, wherein the device is configured to also be configured to screen a drug, antibody, nanoparticle, nucleic acid, RNA-based nanoparticle, metal, vitamin, biomaterial, or nutraceutical/dietary supplement causing an increase or decrease in cultured clot serum sLox-1 relative to untreated cultured clot serum sLox-1, without inducing cell necrosis; with a reasonable expectation of success of screening for agents.
Regarding Claim 18, the instant Claim 18 further recites, “the drug is a chemotherapeutic agent intended to induce apoptosis”, which merely states the name of the drug configured by the device of Claim 17, and does not require use of the drug in the method step. Therefore, dependent Claim 18 is rejected with the claim in which it depends, Claim 17.
Regarding Claims 19-22 and 24, Configuration is interpreted as functional language describing the intended use or intended capability of the device, and not a structural limitation (see Claim Interpretation above). Instant Claim 19 recites,” the drug is configured to decrease ADAM17 activity and TNF activation”; instant Claim 20 recites, “the drug is configured to suppress TNF expression or activity”; instant Claim 21 recites, “the drug comprises a serine- threonine phosphatase inhibitor”; instant Claim 22 recites, “the drug comprises beta glycerol phosphate”; and instant Claim 24 recites, “the drug is configured to alter polymorphonuclear myeloid derived suppressor cell activity or viability. Claims 19-22 and 24 merely state the drug configuration functions, and the instant claims do not require use of the drug in the method step. Therefore, the instant Claims are rejected with the claim in which they depend, Claim 17.
Conclusion
No claims are allowed.
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/ENOSAKHARE ERHUNMWUNSEE/Examiner, Art Unit
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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