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 .
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.
Claim Objections
Claims 18 and 33 are objected to because of the following informalities:
It appears the limitation of claim 18, “and once intracellular phosporylated protein” should recite “and one intracellular phosphorylated protein”; and
Claim 33 is directed toward a kit, however, the second line recites “the method comprising”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 10-24 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.
The term “significantly above” in claim 10 is a relative term which renders the claim indefinite. The term “significantly above” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The disclosure of the invention fails to define what would be considered “significantly above negative control values”. It is twice the value? Three times? Therefore, the threshold for treating the subject is unclear.
Claims 11-24 are rejected for being dependent on independent claim 10.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-24 and 39-55 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to judicial exceptions without significantly more.
Claims 1-9 and 55:
Step 1: Claims 1-9 and 55 are directed toward a process and thus fall within one of the four statutory categories of invention (see MPEP 2106.03 I. The Four Categories).
Step 2A Prong 1: Independent, instant claim 1 recites the limitation “determining the rate of change between the first and second time periods” which under its broadest reasonable can be performed in the mind, falling under the mental processes grouping of abstract ideas, and thus the claims recites a judicial exception (see MPEP 2106.04(a) III. Mental Processes).
Step 2A Prong 2: The judicial exception of claim 1 is not integrated into a practical application because after the determining step, nothing else is done. Furthermore, the additional steps of stimulating basophil cells in vitro and subjected a first and second blood sample to analysis amounts to mere data gathering which is an insignificant extra-solution activity (see MPEP 2106.05(g) Insignificant Extra-Solution Activity) and the courts have held that adding an insignificant extra-solution activity to the judicial exception fails to integrate said judicial exception into a practical application (see MPEP 2106.04(d) Integration of a Judicial Exception Into A Practical Application). Dependent claims 2-9 and 55 merely further limit the insignificant extra-solution activity of data gathering.
Step 2B: While the exact method steps of claim 1 appear to be well-understood routine or conventional (WURC) in the art, the steps of obtaining blood samples, subjecting those samples to a process for basophil stimulation in vitro for a period of time and analyzing the basophil cell activation is WURC as evidenced by primary reference United States Patent Application Publication US 2023/0349890 to Behrends et al. The difference between the instant application and Behrends is stimulating a first blood sample for a period of time and stimulating a second blood sample for a second period of time from the same subject to determine the rate of change of basophil activation between the first and second samples. However, as mentioned above in regards to Step 2A, the stimulating steps are mere data gathering and per MPEP 2106.05 Eligibility Step 2B: Whether a Claim Amounts to Significantly More, an insignificant extra-solution activity cannot qualify as significantly more. Furthermore, the judicial exception itself (i.e., the determining step) cannot be the reason for patentability (see MPEP 2106.04 Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception). Dependent claims 2-9 and 55 fail to provide additional steps/structure that would amount to significantly more than the judicial exception.
Therefore, claims 1-9 and 55 are not patent eligible.
Claims 10-24:
Step 1: Claims 10-24 are directed toward a process and thus fall within one of the four statutory categories of invention (see MPEP 2106.03 I. The Four Categories).
Step 2A Prong 1: Independent, instant claim 10 recites the limitation “determining a rate of basophil activation by determining a change in amount of one or more markers” which under its broadest reasonable can be performed in the mind, falling under the mental processes grouping of abstract ideas, and thus the claims recites a judicial exception (see MPEP 2106.04(a) III. Mental Processes).
Step 2A Prong 2: The judicial exception of claim 10 is not integrated into a practical application because while there is a treating step following the determination step, the treatment is not sufficiently particular see MPEP 2106.04(d)(2) Particular Treatment and Prophylaxis in Step 2A Prong Two). The treatment of “desensitizing immunotherapy toward the allergen” is extremely generalized and not particular to the rate of basophil activation. Furthermore, the “significantly above negative control values” is unclear what threshold is being used to direct treatment. The additional steps of stimulating basophil cells in vitro and measuring one or more biomarkers of basophil activation amounts to mere data gathering which is an insignificant extra-solution activity (see MPEP 2106.05(g) Insignificant Extra-Solution Activity) and the courts have held that adding an insignificant extra-solution activity to the judicial exception fails to integrate said judicial exception into a practical application (see MPEP 2106.04(d) Integration of a Judicial Exception Into A Practical Application). Dependent claims 11-24 merely further limit the insignificant extra-solution activity of data gathering.
Step 2B: While the exact method steps of claim 10 appear to be well-understood routine or conventional (WURC) in the art, the steps of obtaining blood samples, subjecting those samples to a process for basophil stimulation in vitro for a period of time, analyzing the basophil cell activation, and treating with desensitizing immunotherapy to an allergen is WURC as evidenced by primary reference United States Patent Application Publication US 2023/0349890 to Behrends et al. The difference between the instant application and Behrends is stimulating a first blood sample for a period of time and stimulating a second blood sample for a second period of time from the same subject to determine the rate of change of basophil activation between the first and second samples. However, as mentioned above in regards to Step 2A, the stimulating steps are mere data gathering and, per MPEP 2106.05 Eligibility Step 2B: Whether a Claim Amounts to Significantly More, an insignificant extra-solution activity cannot qualify as significantly more. Furthermore, the judicial exception itself (i.e., the determining step) cannot be the reason for patentability (2106.04 Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception). Dependent claims 11-24 fail to provide additional steps/structure that would amount to significantly more than the judicial exception.
Therefore, claims 10-24 are not patent eligible.
Claims 39-54:
Step 1: Claims 39-54 are directed toward a process and thus fall within one of the four statutory categories of invention (see MPEP 2106.03 I. The Four Categories).
Step 2A Prong 1: Independent, instant claim 39 recites the limitation “determining a rate of basophil activation by determining a change in amount of one or more markers” which under its broadest reasonable can be performed in the mind, falling under the mental processes grouping of abstract ideas, and thus the claims recites a judicial exception (see MPEP 2106.04(a) III. Mental Processes).
Step 2A Prong 2: The judicial exception of claim 39 is not integrated into a practical application because after the determining step, nothing else is done. The additional steps of stimulating basophil cells in vitro and measuring one or more biomarkers of basophil activation amounts to mere data gathering which is an insignificant extra-solution activity (see MPEP 2106.05(g) Insignificant Extra-Solution Activity) and the courts have held that adding an insignificant extra-solution activity to the judicial exception fails to integrate said judicial exception into a practical application (see MPEP 2106.04(d) Integration of a Judicial Exception Into A Practical Application). Dependent claims 40-53 merely further limit the insignificant extra-solution activity of data gathering. Dependent claim 54 recites a treating step, however, the treatment is not sufficiently particular (see MPEP 2106.04(d)(2) Particular Treatment and Prophylaxis in Step 2A Prong Two). The treatment of “the subject is recommended for desensitization immunization therapy” is extremely generalized and not particular to the rate of basophil activation.
Step 2B: While the exact method steps of claim 39 appear to be well-understood routine or conventional (WURC) in the art, the steps of obtaining blood samples, subjecting those samples to a process for basophil stimulation in vitro for a period of time, and analyzing the basophil cell activation is WURC as evidenced by primary reference United States Patent Application Publication US 2023/0349890 to Behrends et al. The difference between the instant application and Behrends is stimulating a first blood sample for a period of time and stimulating a second blood sample for a second period of time from the same subject to determine the rate of change of basophil activation between the first and second samples. However, as mentioned above in regards to Step 2A, the stimulating steps are mere data gathering and, per MPEP 2106.05 Eligibility Step 2B: Whether a Claim Amounts to Significantly More, an insignificant extra-solution activity cannot qualify as significantly more. Furthermore, the judicial exception itself (i.e., the determining step) cannot be the reason for patentability (2106.04 Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception). Dependent claims 40-54 fail to provide additional steps/structure that would amount to significantly more than the judicial exception.
Therefore, claims 39-54 are not patent eligible.
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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-13, 15-16, 19-42, 44-45, and 48-54 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2023/0349890 to Behrends et al. (herein Behrends) with a PCT filing date of 19 August 2021 in view of United States Patent Application Publication US 2005/0003461 to Buehring.
Regarding claims 1 and 3-5, Behrends discloses a method for the determination of basophil activation in a sample, induced in vitro, wherein the sample is obtained from a subject who has a known response to an allergen, comprising:
Providing a sample of said subject, wherein the sample is a blood sample;
Treating/stimulating the sample with a test substance for a standard period of time, wherein the test substance is an allergen;
Adding a mixture of antibodies each labeled with a different fluorochrome, said mixture containing the labeled antibodies anti-CD63, anti-CD203c and anti-FcεRIα, and incubating said mixture with said sample;
Measuring the labelled sample by flow cytometry; and
Determining basophil activation based on the analysis of the measured samples and obtained data by flow cytometry-based measurement (see [0012-0017], [0034], [0062], [0073], [0126]).
Behrends discloses the test substance is added in suitable amounts to the sample, wherein suitable amounts are well known to those skilled in the art (see [0068]) (i.e., a selected concentration of the allergen of interest).
However, Behrends fails to disclose “stimulating basophils in vitro in a second blood sample of the subject by contacting the basophil cells with the selected concentration of the allergen of interest for a second period of time” or “determining the rate of change between the first and second time periods” as recited in the instant claim.
Buehring discloses stimulating blood samples from allergic patients with IL-3 for different periods of time (at least four); incubating with an allergen; incubating with an antibody; and measuring and comparing the rate of change of E-NPP3 determined by fluorescent intensity, which is directly linked to basophil activation, between samples stimulated for different periods of time with IL-3 (see [0052-0057]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Behrends to include a second, third, and/or fourth stimulation step, wherein the in vitro basophil cells of a second, third, and or fourth sample are stimulated with the allergen of interest for a second, third, and/or fourth period of time and determining the rate of change between the first, second, third, and/or fourth samples at the different periods of time for the benefit of optimizing stimulating time (see [0059-0061] of Buehring). While in Buehring, IL-3 was used for stimulating at least a first and second sample for at least a first and second period of time, prior to adding the allergen itself, there is a direct correlation to IL-3 in the body and the body’s immune response and IL-3 is a key cytokine in basophil activation, therefore adjusting the allergen stimulating step by stimulating a first sample and a second sample for a first and second period of time would be obvious from using IL-3.
Regarding claim 2, the combination of references above render obvious the invention of claim 1, however Behrends fails to disclose “wherein the first and second blood samples are formed by withdrawal and quenching of two aliquots from a common stimulation reaction” as recited in the instant claim.
Behrends discloses subjecting at least two samples from a common stimulation reaction to a quenching step (see [0054-0055]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the first and second samples to be formed by withdrawal and quenching of two aliquots from a common stimulation reaction for the benefit controlling reaction time (see [0054-0055] of Buehring).
Regarding claim 6, the combination of references above render obvious the invention of claim 1, and Behrends discloses wherein the allergen is a food allergen (see [0067]).
Regarding claim 7, the combination of references above render obvious the invention of claim 1, and Behrends discloses wherein the allergen is an environmental allergen (see [0067]).
Regarding claim 8, the combination of references above render obvious the invention of claim 1, and Behrends discloses wherein the allergen is peanut protein (see [0101-0102]).
Regarding claim 9, the combination of references above render obvious the invention of claim 1, and Behrends discloses wherein the subject has previously been subjected to desensitization immunization therapy with an allergen (see [0107]-0109]).
Regarding claims 10, 12-13 and 19-20, Behrends discloses a method for the determination of basophil activation in a sample, induced in vitro, wherein the sample is obtained from a subject who has a known response to an allergen, comprising:
Providing a sample of said subject, wherein the sample is a blood sample;
Treating/stimulating the sample with a test substance for a standard period of time, wherein the test substance is an allergen;
Adding a mixture of antibodies each labeled with a different fluorochrome, said mixture containing the labeled antibodies anti-CD63, anti-CD203c and anti-FcεRIα, and incubating said mixture with said sample;
Measuring one or more markers of basophil activation bound to the labeled antibodies by flow cytometry;
Determining basophil activation based on the analysis of the measured samples and obtained data by flow cytometry-based measurement (see [0012-0022], [0034], [0062], [0073], [0126]);
comparing results to a negative control value of minimum activation (see [0032]) and
treating with desensitizing immunotherapy toward an allergen accordingly (see [0107]-0109]).
Behrends discloses the test substance is added in suitable amounts to the sample, wherein suitable amounts are well known to those skilled in the art (see [0068]) (i.e., a selected concentration of the allergen of interest).
However, Behrends fails to disclose “stimulating basophils in vitro in a second blood sample of the subject by contacting the basophil cells with the selected concentration of the allergen of interest for a second period of time” or “determining a rate of basophil activation by determining a change in amount of the one or more biomarkers between the first and second and second blood samples” as recited in the instant claim.
Buehring discloses stimulating blood samples from allergic patients with IL-3 for different periods of time (at least four); incubating with an allergen; incubating with an antibody; and measuring and comparing the rate of change of E-NPP3 determined by fluorescent intensity, which is directly linked to basophil activation, between samples stimulated for different periods of time with IL-3 (see [0052-0057]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Behrends to include a second, third, and/or fourth stimulation step, wherein the in vitro basophil cells of a second, third, and or fourth sample are stimulated with the allergen of interest for a second, third, and/or fourth period of time and determining a rate of basophil activation by determining a change in an amount of one or more biomarkers between the first, second, third, and/or fourth samples for the benefit of optimizing stimulating time (see [0059-0061] of Buehring). While in Buehring, IL-3 was used for stimulating at least a first and second sample for at least a first and second period of time, prior to adding the allergen itself, there is a direct correlation to IL-3 in the body and the body’s immune response and IL-3 is a key cytokine in basophil activation, therefore adjusting the allergen stimulating step by stimulating a first sample and a second sample for a first and second period of time would be obvious from using IL-3.
Regarding claim 11, the combination of references above render obvious the invention of claim 10, however Behrends fails to disclose “wherein the first and second blood samples are formed by withdrawal and quenching of two aliquots from a common stimulation reaction” as recited in the instant claim.
Behrends discloses subjecting at least two samples from a common stimulation reaction to a quenching step (see [0054-0055]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the first and second samples to be formed by withdrawal and quenching of two aliquots from a common stimulation reaction for the benefit controlling reaction time (see [0054-0055] of Buehring).
Regarding claim 15-16, the combination of references above render obvious the invention of claim 10, and Behrends discloses measuring CD63 and CD203c (i.e., cell surface markers) (see [0021]).
Regarding claim 21, the combination of references above render obvious the invention of claim 10, and Behrends discloses wherein the allergen is a food allergen (see [0067]).
Regarding claim 22, the combination of references above render obvious the invention of claim 10, and Behrends discloses wherein the allergen is an environmental allergen (see [0067]).
Regarding claim 23, the combination of references above render obvious the invention of claim 10, and Behrends discloses wherein the allergen is peanut protein (see [0101-0102]).
Regarding claim 24, the combination of references above render obvious the invention of claim 10, and Behrends discloses wherein the subject has previously been subjected to desensitization immunization therapy with an allergen (see [0107]-0109]).
Regarding claims 25 and 27-28, Behrends discloses a set of assay samples (see [0148]) to aid in determining likelihood of a subject having an allergic reaction against an allergen of interest (see [0012-0022] and [0064-0065), the set comprising:
a plurality of assay samples comprising at least a first blood sample and a second blood sample formed by stimulating in vitro basophil cells in a first blood sample of the subject by contacting the basophil cells with a selected concentration of the allergen of interest, wherein the plurality of assay samples are suitable for measuring one or more biomarkers of basophil activation in the blood samples whereby a rate of basophil activation can be determined and comparing the differences in amount of the one or more biomarkers of the blood samples (see [0012-0017], [0034], [0062], [0073], [0126], [0148]). Behrends discloses the test substance is added in suitable amounts to the sample, wherein suitable amounts are well known to those skilled in the art (see [0068]) (i.e., a selected concentration of the allergen of interest).
However, Behrends fails to disclose “stimulating basophils in vitro in a second blood sample of the subject by contacting the basophil cells with the selected concentration of the allergen of interest for a second period of time” as recited in the instant claim.
Buehring discloses stimulating blood samples from allergic patients with IL-3 for different periods of time (at least four); incubating with an allergen; incubating with an antibody; and measuring and comparing the rate of change of E-NPP3 determined by fluorescent intensity, which is directly linked to basophil activation, between samples stimulated for different periods of time with IL-3 (see [0052-0057]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Behrends to include a second, third, and/or fourth stimulation step, wherein the in vitro basophil cells of a second, third, and or fourth sample are stimulated with the allergen of interest for a second, third, and/or fourth period of time and determining the rate of change between the first, second, third, and/or fourth samples at the different periods of time for the benefit of optimizing stimulating time (see [0059-0061] of Buehring). While in Buehring, IL-3 was used for stimulating at least a first and second sample for at least a first and second period of time, prior to adding the allergen itself, there is a direct correlation to IL-3 in the body and the body’s immune response and IL-3 is a key cytokine in basophil activation, therefore adjusting the allergen stimulating step by stimulating a first sample and a second sample for a first and second period of time would be obvious from using IL-3.
Note that the “suitable for” clause does not further limit the set of assay samples themselves and as long as the prior art renders obvious the assay samples themselves they would be considered suitable for the disclosed purpose.
Regarding claim 26, the combination of references above render obvious the invention of claim 25, however Behrends fails to disclose “wherein the first and second blood samples are formed by withdrawal and quenching of two aliquots from a common stimulation reaction” as recited in the instant claim.
Behrends discloses subjecting at least two samples from a common stimulation reaction to a quenching step (see [0054-0055]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the first and second samples to be formed by withdrawal and quenching of two aliquots from a common stimulation reaction for the benefit controlling reaction time (see [0054-0055] of Buehring).
Regarding claim 29, the combination of references above render obvious the invention of claim 25, and Behrends discloses wherein the allergen is a food allergen (see [0067]).
Regarding claim 30, the combination of references above render obvious the invention of claim 25, and Behrends discloses wherein the allergen is an environmental allergen (see [0067]).
Regarding claim 31, the combination of references above render obvious the invention of claim 25, and Behrends discloses wherein the allergen is peanut protein (see [0101-0102]).
Regarding claim 32, the combination of references above render obvious the invention of claim 25, and Behrends discloses wherein the subject has previously been subjected to desensitization immunization therapy with an allergen (see [0107]-0109]).
Regarding claims 33 and 36-38, Behrends discloses a test kit for performing basophil activation in a subject comprising: anti-CD63, anti-CD203c and anti-FcεRIα antibodies, each labeled with a distinct fluorochrome; one or more test substances used for activating the basophils, wherein the test substance is an allergen (see [0064-0065]; [0095-0097]); and wherein basophil activation kits comprise a plurality tubes for holding blood samples (see [0154]). Behrends discloses the test substance is added in suitable amounts to the sample, wherein suitable amounts are well known to those skilled in the art (see [0068]) (i.e., a selected concentration of the allergen of interest). The provided test substances, antibodies, etc. would have to be in predetermined amounts in separate packages to be added to the blood samples to control activation and avoid cross-contamination of desired allergy responses.
Behrends fails to disclose “a quenching agent for stopping the stimulation of basophils” as recited in the instant claim.
Behrends discloses subjecting at least two samples from a common stimulation reaction to a quenching step by adding a quenching agent to stop the stimulation of basophils (see [0054-0055]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the kit of Behrends to comprise a quenching agent to stop then stimulation of basophils for the benefit controlling reaction time (see [0054-0055] of Buehring).
Regarding claim 34, the combination of references above render obvious the invention of claim 33. Behrends fails to explicitly disclose that the kit comprises a timer, however, Behrend discloses incubating the samples with antibodies for a sufficient period of time to allow binding to specific target molecules (see [0072]) and the only way to track whether the time is sufficient or not would be to use a timer.
Regarding claim 35, , the combination of references above render obvious the invention of claim 33, Behrends fails to explicitly disclose that the kit comprises a plurality of timers, however, Behrend discloses incubating the samples with antibodies for a sufficient period of time to allow binding to specific target molecules (see [0072]) and the only way to track whether the time is sufficient or not would be to use a timer and the MPEP 2144.04 VI. Duplication of Parts states that the mere duplication of a part has no patentable significance unless a new and unexpected results is produced. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the kit to comprise multiple timers for the benefit of monitoring more than one sample time.
Regarding claims 39, 41-42 and 48-49, Behrends discloses a method for the determination of basophil activation in a sample, induced in vitro, wherein the sample is obtained from a subject who has a known response to an allergen, comprising:
Providing a sample of said subject, wherein the sample is a blood sample;
Treating/stimulating the sample with a test substance for a standard period of time, wherein the test substance is an allergen;
Adding a mixture of antibodies each labeled with a different fluorochrome, said mixture containing the labeled antibodies anti-CD63, anti-CD203c and anti-FcεRIα, and incubating said mixture with said sample;
Measuring one or more markers of basophil activation bound to the labeled antibodies by flow cytometry;
Determining basophil activation based on the analysis of the measured samples and obtained data by flow cytometry-based measurement (see [0012-0022], [0034], [0062], [0073], [0126]).
Behrends discloses the test substance is added in suitable amounts to the sample, wherein suitable amounts are well known to those skilled in the art (see [0068]) (i.e., a selected concentration of the allergen of interest).
However, Behrends fails to disclose “stimulating basophils in vitro in a second blood sample of the subject by contacting the basophil cells with the selected concentration of the allergen of interest for a second period of time” or “determining a rate of basophil activation by determining a change in amount of the one or more biomarkers between the first and second and second blood samples” as recited in the instant claim.
Buehring discloses stimulating blood samples from allergic patients with IL-3 for different periods of time (at least four); incubating with an allergen; incubating with an antibody; and measuring and comparing the rate of change of E-NPP3 determined by fluorescent intensity, which is directly linked to basophil activation, between samples stimulated for different periods of time with IL-3 (see [0052-0057]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Behrends to include a second, third, and/or fourth stimulation step, wherein the in vitro basophil cells of a second, third, and or fourth sample are stimulated with the allergen of interest for a second, third, and/or fourth period of time and determining a rate of basophil activation by determining a change in an amount of one or more biomarkers between the first, second, third, and/or fourth samples for the benefit of optimizing stimulating time (see [0059-0061] of Buehring). While in Buehring, IL-3 was used for stimulating at least a first and second sample for at least a first and second period of time, prior to adding the allergen itself, there is a direct correlation to IL-3 in the body and the body’s immune response and IL-3 is a key cytokine in basophil activation, therefore adjusting the allergen stimulating step by stimulating a first sample and a second sample for a first and second period of time would be obvious from using IL-3.
Regarding claim 40, the combination of references above render obvious the invention of claim 39, however Behrends fails to disclose “wherein the first and second blood samples are formed by withdrawal and quenching of two aliquots from a common stimulation reaction” as recited in the instant claim.
Behrends discloses subjecting at least two samples from a common stimulation reaction to a quenching step (see [0054-0055]).
Buehring and Behrends are analogous in the field of detecting allergies in a blood sample based on basophil activation. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the first and second samples to be formed by withdrawal and quenching of two aliquots from a common stimulation reaction for the benefit controlling reaction time (see [0054-0055] of Buehring).
Regarding claim 44-45, the combination of references above render obvious the invention of claim 39, and Behrends discloses measuring CD63 and CD203c (i.e., cell surface markers) (see [0021]).
Regarding claim 50, the combination of references above render obvious the invention of claim 39, and Behrends discloses wherein the allergen is a food allergen (see [0067]).
Regarding claim 51, the combination of references above render obvious the invention of claim 39, and Behrends discloses wherein the allergen is an environmental allergen (see [0067]).
Regarding claim 52, the combination of references above render obvious the invention of claim 39, and Behrends discloses wherein the allergen is peanut protein (see [0101-0102]).
Regarding claim 53, the combination of references above render obvious the invention of claim 39, and Behrends discloses wherein the subject has previously been subjected to desensitization immunization therapy with an allergen (see [0107]-0109]).
Regarding claim 54, the combination of references above render obvious the invention of claim 39, and Behrends discloses treating with desensitizing immunotherapy toward an allergen accordingly (see [0107]-0109]).
Claims 14, 17-18, 43, and 46-47 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2023/0349890 to Behrends et al. (herein Behrends) with a PCT filing date of 19 August 2021 in view of United States Patent Application Publication US 2005/0003461 to Buehring and in further view of International Publication WO 2015/057402 to Shankey et al. (herein Shankey).
Regarding claims 14 and 17, the combination of references above render obvious the invention of claim 10, however, Behrends fails to disclose “wherein the one or more markers are intracellular phosphorylated proteins” as recited in the instant claim.
Shankey discloses a method of detecting and monitoring proteasome activity in target cells that involves activating one or more target cells in a biological sample, contacting the activated sample with a labeled binding agent capable of binding to the activating agent and detecting proteasome activity in target cells using a flow cytometer (see pgs. 3-4, line 29-line 5), wherein the target cell is basophils (see pg. 11, lines 31-33) and the proteasome activity is related to an allergy (see pgs. 13-14, line 33-line 7). Shankey discloses wherein labeled binding agents (i.e., one or more biomarkers) like AKT and/or S6 in phosphorylated form (see pg. 4, lines 23-30), which reads on intracellular phosphorylated proteins, are well known in art. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the one or more biomarkers to be phospho AKT and/or phospho S6 as they are suitable biomarkers for basophil activation (see MPEP 2144.07 Art Recognized Suitability for an Intended Purpose) for the benefit of particular allergen detection.
Regarding claim 18, the combination of references above render obvious the invention of claim 10, and Behrends discloses measuring CD63 and CD203c (i.e., cell surface markers) (see [0021]) but fails to disclose “one phosphorylated protein are measured” as recited in the instant claim.
Shankey discloses a method of detecting and monitoring proteasome activity in target cells that involves activating one or more target cells in a biological sample, contacting the activated sample with a labeled binding agent capable of binding to the activating agent and detecting proteasome activity in target cells using a flow cytometer (see pgs. 3-4, line 29-line 5), wherein the target cell is basophils (see pg. 11, lines 31-33) and the proteasome activity is related to an allergy (see pgs. 13-14, line 33-line 7). Shankey discloses wherein labeled binding agents (i.e., one or more biomarkers) like AKT and/or S6 in phosphorylated form (see pg. 4, lines 23-30), which reads on intracellular phosphorylated proteins, are well known in art. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to measure an intracellular phosphorylated protein as they are suitable biomarkers for basophil activation (see MPEP 2144.07 Art Recognized Suitability for an Intended Purpose) for the benefit of particular allergen detection.
Regarding claims 43 and 46, the combination of references above render obvious the invention of claim 39, however, Behrends fails to disclose “wherein the one or more markers are intracellular phosphorylated proteins” as recited in the instant claim.
Shankey discloses a method of detecting and monitoring proteasome activity in target cells that involves activating one or more target cells in a biological sample, contacting the activated sample with a labeled binding agent capable of binding to the activating agent and detecting proteasome activity in target cells using a flow cytometer (see pgs. 3-4, line 29-line 5), wherein the target cell is basophils (see pg. 11, lines 31-33) and the proteasome activity is related to an allergy (see pgs. 13-14, line 33-line 7). Shankey discloses wherein labeled binding agents (i.e., one or more biomarkers) like AKT and/or S6 in phosphorylated form (see pg. 4, lines 23-30), which reads on intracellular phosphorylated proteins, are well known in art. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date for the one or more biomarkers to be phospho AKT and/or phospho S6 as they are suitable biomarkers for basophil activation (see MPEP 2144.07 Art Recognized Suitability for an Intended Purpose) for the benefit of particular allergen detection.
Regarding claim 47, the combination of references above render obvious the invention of claim 39, and Behrends discloses measuring CD63 and CD203c (i.e., cell surface markers) (see [0021]) but fails to disclose “one phosphorylated protein are contacted with the first and second blood sample” as recited in the instant claim.
Shankey discloses a method of detecting and monitoring proteasome activity in target cells that involves activating one or more target cells in a biological sample, contacting the activated sample with a labeled binding agent capable of binding to the activating agent and detecting proteasome activity in target cells using a flow cytometer (see pgs. 3-4, line 29-line 5), wherein the target cell is basophils (see pg. 11, lines 31-33) and the proteasome activity is related to an allergy (see pgs. 13-14, line 33-line 7). Shankey discloses wherein labeled binding agents (i.e., one or more biomarkers) like AKT and/or S6 in phosphorylated form (see pg. 4, lines 23-30), which reads on intracellular phosphorylated proteins, are well known in art. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to measure an intracellular phosphorylated protein as they are suitable biomarkers for basophil activation (see MPEP 2144.07 Art Recognized Suitability for an Intended Purpose) for the benefit of particular allergen detection.
Claim 55 is rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2023/0349890 to Behrends et al. (herein Behrends) with a PCT filing date of 19 August 2021 in view of United States Patent Application Publication US 2005/0003461 to Buehring and in further view of United States Patent Application Publication US 2023/0364602 to Gilboa-Geffen et al. (herein Gilboa-Geffen) with a PCT filing date 13 October 2021.
Regarding claim 55, the combination of references above render obvious the invention of claim 8, however, Behrends fails to disclose “wherein the allergen is peanut protein component and the peanut protein component is selected from the group consisting of: Arah1, Arah2, Arah6, Arah7, AraH8 and Arah10” as recited in the instant claim.
Gilboa-Geffen discloses an allergen detection system (see abstract) that involves detecting AraH1 in serum (see Example 5) to detect a peanut allergy (see [0356]).
Gilboa-Geffen is analogous to Behrends in the field of allergen detection in blood samples involving peanut protein. Therefore, it would have been obvious to one of ordinary skill in the art to detect Arah1 in blood samples for the benefit of monitoring a peanut allergy (see [0356] of Gilboa-Geffen).
Conclusion
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/KATHRYN ELIZABETH LIMBAUGH/ Primary Examiner, Art Unit 1797