DETAILED ACTION
Claims 1-8 are pending.
Claim Objections
Claims 1, 3, and 8 are objected to because of the following informalities: Improper Markush group.
Claim 1 recites “…wherein, the markers comprise one or more of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152”.
However, the claim should recite proper Markush language i.e., “…wherein, the markers comprise one or more selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152”.
The broadest reasonable interpretation of claim 1 is that the markers must contain at least one of the listed markers (BTLA, GITR HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, or CD 152).
Claim 3 recites “…encoded microspheres coated with one or more capture antibodies of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-LI, TIM-3, CD28, CD80, 4-lBB, CD27, and CD152, respectively, one or more detection antibodies of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD 152…”.
However, the claim should recite proper Markush language i.e., “…wherein encoded microspheres coated with one or more capture antibodies selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-LI, TIM-3, CD28, CD80, 4-lBB, CD27, and CD152, respectively, one or more detection antibodies selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD 152”.
The broadest reasonable interpretation of claim 3 is that the markers must contain at least one of the listed markers (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-LI, TIM-3, CD28, CD80, 4-lBB, CD27, or CD152).
Claim 8 recites “…preparation of encoded microspheres coated with capture antibodies: coupling one or more capture antibodies of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152 with corresponding encoded microspheres, respectively, to obtain encoded microspheres coated with one or more capture antibodies of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152, respectively; preparation of biotin-labeled detection antibodies: ligating a biotin onto one or more detection antibodies of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152, respectively, to obtain one or more detection antibodies of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80,4-1BB, CD27, and CD152 respectively labeled with the biotin”.
However, the claim should recite proper Markush language i.e., “…preparation of encoded microspheres coated with capture antibodies: coupling one or more capture antibodies selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152 with corresponding encoded microspheres, respectively, to obtain encoded microspheres coated with one or more capture antibodies selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152, respectively; preparation of biotin-labeled detection antibodies: ligating a biotin onto one or more detection antibodies selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80, 4-1BB, CD27, and CD152, respectively, to obtain one or more detection antibodies selected from a group consisting of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80,4-1BB, CD27, and CD152 respectively labeled with the biotin”.
The broadest reasonable interpretation of claim 8 is that the markers must contain at least one of the listed markers (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, TIM-3, CD28, CD80,4-1BB, CD27, or CD152).
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.
Claim 2 is 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 2 recites “application of markers of claim 1 in the preparation of a kit for predicting COVID-19 immune checkpoint storm”. However, it is unclear what the “application” refers to. It’s unclear if it is referring to a method of using, a method of making, or a kit. If applicant intends a method delete the term application and replace with “a method of detecting” and add active steps. For the sake of expediting prosecution, the claims are being read to a method of detecting using the markers.
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 1-2 is rejected under 35 U.S.C. 101 because the claimed product and method are directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory category per MPEP 2106.03. In the instant application, claim 1 recites markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152, which are proteins. Because proteins are composed of matter, the markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152 are a composition of matter, which is a statutory category of invention. As explained in the MPEP, it is not necessary to identify a single category into which a claim falls, so long as it is clear that the claim falls into at least one category. MPEP 2106.03(I). Here, because the markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152 are compositions of matter, the claim is to at least one statutory category of invention (Step 1: YES).
Regarding instant claim 2, Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims.
Similarly, instant claim 2 appears to be drawn to an application. According to Merriam webster definition application is act of putting something to use ( https://www.merriam-webster.com/dictionary/application), or in other words a method of using. From the specification, claim 2 appears drawn then to method that at least uses at least one of the following markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152,
Instant claim 2 is directed to a statutory class of a method that applies markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152 for predicting COVID-19 immune checkpoint storm. (Step 1: YES).
Step 2A Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding instant claim 1, Example 44 of the “2019 PEG” shows a similar fact pattern. Claim 1 in example 44 is drawn to denveric acid. The markedly different characteristics analysis is used to determine if the nature-based product limitation is a product of nature exception. MPEP 2106.04(c)(I). Although the claim also recites a non-nature based product limitation (the container), the markedly different characteristics analysis should be applied only to the nature-based product limitation. MPEP 2106.04(c)(I)(A). The markedly different characteristics analysis is performed by comparing the nature-based product limitation in the claim to its naturally occurring counterpart to determine if it has markedly different characteristics from the counterpart. MPEP 2106.04(c)(II). Here, the closest natural counterpart is naturally occurring denveric acid. When the claimed denveric acid is compared to this counterpart, the comparison indicates that there are no differences in structure, function, or other characteristics. Therefore, the claimed denveric acid is a product of nature exception. Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 576, 589-90 (2013) (naturally occurring things are “products of nature” which cannot be patented).”
Similarly, instant claim 1 recites the use of markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152. The closest natural counterpart to markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152 is naturally occurring BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152. When the claimed markers are compared to this counterpart, the comparison indicates that there are no differences in structure, function, or other characteristics. Moreover, the language of “predicting” is drawn to intended use and does not impart markedly different characteristics. Therefore, the claimed markers BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152 are a product of natural exception.
Accordingly, instant claim 1 recites a judicial exception (a product of nature), and the analysis must therefore proceed to Step 2A Prong Two.
Regarding instant claim 2, Example 43 of the “2019 PEG” shows a similar fact pattern.
Regarding claim 1 in Example 43 of the “2019 PEG” and per Step 2A, prong 1, the claim recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” and according to broadest reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or greater and thus is not responding, or will not respond, to glucocorticoids). This limitation therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the 2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be practically performed in the human mind, and is in fact performed in the human mind on a daily basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them complete the recited calculation, the use of such physical aid does not negate the mental nature of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of nature), and the analysis must therefore proceed to Step 2A Prong Two.
Instant claim 2 does not recite any active steps but instant claim 2 recites in the preamble “predicting COVID-19 immune checkpoint storm”, which at best suggests that using the markers are for some form of detection of the marker and ultimately a correlation to the disease. This language predicting” in the preamble, is still directed to a judicial exception as it is an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion)). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Further, instant claim 2 describes a naturally occurring relationship between the nature-based products and correlating it to the prediction of COVID-19 immune checkpoint storm, and thus is considered to recite a law of nature.
Consequently, like example 43, instant claim 2 recites the judicial exception of applying and using a law of nature and an abstract idea.
Accordingly, instant claim 2 recites a judicial exception (a law of nature and an abstract idea that falls within the mental process groupings) and the analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding instant claim 1, Example 44 of the “2019 PEG” shows a similar fact pattern.
In claim 1 of example 44 of the “2019 PEG” and per Step2A, Prong two, the evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. 2019 PEG Section III(A)(2), 84 Fed. Reg. at 54-55. Claim 1 recites an additional element (the container). Although this limitation indicates that the denveric acid is held in the container, it does not provide any information as to how the denveric acid is contained, or what the container is, but instead covers any possible container that a doctor or pharmacist decides to use. Because denveric acid must be placed in a container in order to store and use it, merely reciting a generic “container” thus fails to meaningfully limit the claim because it is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, the container does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception (Step 2A: YES)”.
While example 44 recites a container which still was not deemed sufficient, instant claim 1 does not even recite any container and contains no more than the biomarkers (the natural product). Example 44 did not pass Step 2A prong 2 with an additional element (the container). Accordingly, Instant claim 1 does not have additional elements that would integrate the judicial exceptions cited above into a practical application.
Therefore, claim 1 does not integrate the judicial exception into a practical application.
Regarding instant claim 2, Example 43 of “2019 PEG” shows a similar fact pattern.
In claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Besides the abstract idea, the claim 1 of example 43 of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient having a non-responder phenotype”. Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. In fact, this limitation is recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome (the patient’s phenotype) into account when deciding which treatment to administer, making the limitation’s inclusion in this claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
Similarly, instant claim 2 does not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison to claim 43, Example 43 did not pass step 2A prong 2 with step of general treatment, instant claim 2 does not even recite any steps of treatment. Example 43 failed with the step of general treatment, instant claim 2 does not even have an active step, let alone a step for treatment. instant claim 2 does not recite any additional elements other than the abstract idea and law of nature. Instant claim 2 recites the judicial exceptions without any active steps, therefore, instant claim 2 does not integrate the judicial exception into a practical application because they do not amount to more than the judicial exceptions themselves, analogous to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012). Furthermore, the claims do not act on or use the judicial exceptions in any further steps as required by MPEP 2106.04(d). Instant claim 2 recites the application of biomarkers (law of nature), and the natural correlation of biomarkers and diseases (law of nature). Further, instant claim 2 recites “predicting” which falls within an abstract idea as it can practically be performed in the human mind.
Therefore, claim 2 does not integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
Regarding instant claim 1, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As discussed with respect to Step 2A Prong Two, the claim does not even recite a container or any additional elements. (Step 2B: NO). The claim is not eligible.
Regarding instant claim 2, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim does not recite any active steps. Instant claim 2 does recite “predicting” in the preamble, that language is still directed to a judicial exception as it is an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion)). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Further, instant claim 2 describes a naturally occurring relationship between the nature-based products and correlating it to the prediction of COVID-19 immune checkpoint storm, and thus is considered to recite a law of nature. Accordingly, instant claim 2 is not eligible (Step 2B: NO).
Thus, instant claims 1-2 are rejected under 35 USC 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
1. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Julia et al.,"Blocking of the CD80/86 axis as a therapeutic approach to prevent progression to more severe forms of COVID-19" (2020). https://doi.org/10.48550/arXiv.2005.1005
Regarding claim 1, Julia teaches markers for predicting Coronavirus disease 2019 (COVID-19) immune checkpoint storm (see abstract where Julia teaches that cytokine storms can cause multiple organ damage and death and the need to identify therapies to treat and prevent severe symptoms during COVID-19), wherein,
the markers comprise one or more of BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27, and CD 152 (see page 3 where Julia teaches that in severe COVID-19, T cells can become hyperactivated due to excessive activation though the CD80/86 axis. See page 3 where Julia further teaches that blocking the CD80/86 axis could be a useful therapeutic approach to reduce the level of macrophage-associated inflammatory response in COVID-19. See page 9 where Julia teaches there is evidence to support the link between the relevance of CD80/86 axis to COVID-19).
2. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al., “Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients”. Journal for ImmunoTherapy of Cancer. 2019;7:334.https://doi.org/10.1186/s40425-019-0810-y (2019).
Regarding claim 1, Wang teaches immune checkpoint markers being BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD- L1, TIM-3, CD28, CD80, 4-IBB, CD27 (see abstract “We profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay.”).
3.Claims 1-2 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Coric et al., (US 10392442 B2) (2019).
Regarding claim 1, Coric teaches markers PD-1 and CD27 for detecting cancer (see column 15 lines 59-62 and see column 14 lines 5-15).
Regarding claim 2, Coric teaches a kit containing PD-1 and CD27 for detecting cancer (see column 29 lines 57-67 and column 30 lines 4-12).
The use of the markers specifically for predicting COVID-19 immune checkpoint storm is considered intended use. The claimed markers are no different than Coric’s markers.
4.Claims 1-3, and 6-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chinese Patent: CN110456042A (2019).
Regarding claim 1, ‘042 teaches a kit containing markers comprising one or more of PD-L1, CD28, and TIM-3 for predicting cancer immunotherapy effects (see claim 4 “a kind of for predicting the kit or chip of cancer immunotherapy effect, which is characterized in that the kit or chip Detection reagent including any one or more following Serology biological marker: MIP-1beta, SDF-1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10.”).
Regarding claim 2, ‘042 teaches a kit containing PD-LI, TIM-3, CD28 for predicting cancer immunotherapy effects (see claim 5).
The use of the markers specifically for predicting COVID-19 immune checkpoint storm is considered intended use. The claimed markers are no different than ‘042’s markers. Regarding claim 3, ‘042 teaches the kit comprises: encoded microspheres coated with one or more capture antibodies of PD-LI, TIM-3, CD28 (see claim 5 “kit according to claim 4 or chip, which is characterized in that the detection reagent is antibody, it is preferable that institute State the capture antibody that kit includes any one or more following Serology biological marker: MIP-1beta, SDF- 1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10”), respectively,
one or more detection antibodies of PD-LI, TIM-3, CD28 (see claim 5 “kit according to claim 4 or chip, which is characterized in that the detection reagent is antibody, it is preferable that institute State the capture antibody that kit includes any one or more following Serology biological marker: MIP-1beta, SDF- 1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10”),
labeled respectively with a biotin (see claim 8 “kit according to claim 7 or chip, which is characterized in that the detection antibody is marked with detection, Preferably, the detection is labeled as biotin labeling; It is highly preferred that the biotin labeling is the biotin labeling of N- carboxylic succinimide activation.”), and
streptavidin- labeled phycoerythrin (see page 7 under Embodiment 1 “For MIP-1beta, SDF-1alpha, PD-L1, CD28, TIM-3, RANTES, IP-10 biological marker analyte detection Liquid phase chip reagent box preparation. One, kit forms:
(1) coating capture antibody coding microball: containing respectively be coated with MIP-1beta, SDF-1alpha, PD-L1, The coding microball of CD28, TIM-3, RANTES, IP-10 capture antibody；
(2) biotin labeling detects antibody: MIP-1beta, SDF-1alpha for being marked respectively with biotin, PD-L1, CD28, TIM-3, RANTES, IP-10 detect antibody；
(3) streptavidin phycoerythrin.”).
Regarding claim 6, ‘042 teaches wherein, the encoded microspheres comprise carboxyl microspheres (see claim 11 “preparation method according to claim 10, which is characterized in that the preparation method includes:
Obtain the antibody of any one or more following Serology biological marker: MIP-1beta, SDF-1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10；
Preferably, by the Antibody preparation at capture antibody and/or detection antibody；
Preferably, the capture antibody is coated on solid phase carrier, it is highly preferred that it is micro- that the capture antibody is coated in coding on ball, it is further preferred that the capture antibody is coated on carboxyl coding microball；
Preferably, make the detection antibody with detection label, it is highly preferred that the detection antibody is made to have biotin labeling, It is further preferred that the detection antibody is made to have the biotin labeling that N- carboxylic succinimide activates.”, ‘042 refers to microspheres as microballs).
Regarding claim 7, ‘042 teaches wherein, the biotin comprises N-carboxyl succinimide-activated biotin (see claim 11 “…Preferably, make the detection antibody with detection label, it is highly preferred that the detection antibody is made to have biotin labeling, It is further preferred that the detection antibody is made to have the biotin labeling that N- carboxylic succinimide activates.”).
Regarding claim 8, ‘042 teaches a method for preparing the kit according to any one of claims 3 to 7, comprising the following steps:
preparation of encoded microspheres coated with capture antibodies:
coupling one or more capture antibodies of PD-L1, CD28, and TIM-3 (see claim 5 “kit according to claim 4 or chip, which is characterized in that the detection reagent is antibody, it is preferable that institute State the capture antibody that kit includes any one or more following Serology biological marker: MIP-1beta, SDF- 1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10…”),
with corresponding encoded microspheres, respectively, to obtain encoded microspheres coated with one or more capture antibodies of PD-L1, CD28, and TIM-3 (see claim 11 “preparation method according to claim 10, which is characterized in that the preparation method includes:
Obtain the antibody of any one or more following Serology biological marker: MIP-1beta, SDF-1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10；
Preferably, by the Antibody preparation at capture antibody and/or detection antibody；
Preferably, the capture antibody is coated on solid phase carrier, it is highly preferred that it is micro- that the capture antibody is coated in coding on ball, it is further preferred that the capture antibody is coated on carboxyl coding microball…”), respectively;
preparation of biotin-labeled detection antibodies: ligating a biotin onto one or more detection antibodies PD-L1, CD28, and TIM-3 (see claim 11 “Obtain the antibody of any one or more following Serology biological marker: MIP-1beta, SDF-1alpha, PD-L1, CD28, TIM-3, RANTES and IP-10… Preferably, make the detection antibody with detection label, it is highly preferred that the detection antibody is made to have biotin labeling, It is further preferred that the detection antibody is made to have the biotin labeling that N- carboxylic succinimide activates.”), respectively,
to obtain one or more detection antibodies of PD-L1, CD28, and TIM-3 respectively labeled with the biotin (see claim 11).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
5. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Chinese Patent: CN110456042A (2019) as applied to claims 1-3 and 6-8 above, and in view of DeFrances et al., Inhibition of T-cell activation by PIK3IP1.” European journal of immunology vol. 42,10 (2012): 2754-9. doi:10.1002/eji.201141653 (2012).
The teachings of CN110456042A are discussed in the 35 USC 102 rejection above. CN110456042A is silent towards the clone antibodies being used.
Regarding claim 4, DeFrances teaches the use of biotinylated human antibodies for CD28, clone 10F3 (see page 2757 “Biotinylated antibodies to human and mouse CD28(10F3 and 37.51, respectively) and mouse CD3 (2C11), as wellas streptavidin were from Invitrogen (Carlsbad, CA, USA).”).
It would have been prima facia obvious, at the time of the instant application, to use the clone number 10F3 for CD28 as taught by DeFrances, with the detection kit of CN110456042A . The use of biotinylated antibodies for CD28 in detection assays was known in the art at the time of the instant application. DeFrances teaches successful use of 10F3 in figures 1 and 2. DeFrances further teaches that CD28 plays an important role in T-cell activation (see page 2755). One of ordinary skill in the art would have been motivated at the time of the instant application to measure CD28 to monitor COVID-19 immune checkpoint storm because CD28 plays an important role in the immune system and T-cell activation. The artisan would have had reasonable expectation of success for using 10D3, as it has been shown in the past to be successful.
6. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Chinese Patent: CN110456042A (2019) as applied to claims 1-3 and 6-8 above, and in view of Levy et al., “Superantigens hyperinduce inflammatory cytokines by enhancing the B7-2/CD28 costimulatory receptor interaction.” Proceedings of the National Academy of Sciences of the United States of America vol. 113,42 (2016): E6437-E6446. doi:10.1073/pnas.1603321113 (2016).
The teachings of CN110456042A are discussed in the 35 USC 102 rejection above. CN110456042A is silent towards the clone antibodies being used.
Regarding claim 5, Levy teaches the use of clone number 37407 for CD28 (see page E6445 “mouse monoclonal αCD28 (clone 37407)”).
It would have been prima facia obvious, at the time of the instant application, to use clone number 37407 for CD28 as taught by Levy, with the detection kit of CN110456042A. The use of clone number 37407 for CD28 in detection assays was known in the art at the time of the instant application. Levy teaches the successful use of 37407 (see figure 5). Levy teaches that CD28 is a critical regulator of the immune response (see page E6437). Levy teaches that the inflammatory cytokine response is indispensable for protective immunity, yet bacterial and viral infections often elicit an exaggerated response (“cytokine storm”) harmful to the host (see page E6437). Further, Levy teaches that T-cell activation by superantigens requires their direct binding to CD28, the second signaling molecule mandatory for T-cell activation, which results in massive induction of inflammatory cytokines that mediate toxic shock (see page E6437). One of ordinary skill in the art would have been motivated at the time of the instant application to measure CD28 to monitor for COVID-19 immune checkpoint storm because CD28 plays an important role in the immune system and cytokine storms. The artisan would have had reasonable expectation of success for using 37407, as it has been down in the past to be successful.
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678