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 .
Priority
The present application, filed on 01/31/2024, claims benefit of U.S. Provisional Application No. 63/442,633, filed on 02/01/2023.
The content in this application is supported in the original disclosure provided in U.S. Provisional Application No. 63/442,633, filed on 02/01/2023, thus instant claims 1-19 have an effective filing date of 02/01/2023.
Information Disclosure Statement
Fours Information Disclosure Statement(s) (IDSs), filed on 05/15/2024, 06/19/2024, 04/10/2026, and 05/22/2026, are acknowledged and considered. One reference is stricken for the reasons detailed herein below.
NPL Cite No. 2, Turner et al., provided in IDS filed on 05/22/2026, is stricken because it is not provided.
Claim Status
Claims 1-19 are pending and examined herein below.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 1A, 4B, 4C, and 6 (all three graphs) are blurry and/or not fully legible. It is suggested that these figures be replaced with fully legible versions.
Further, Figures 2 and 6 have multiple parts that are not labeled. For example, Figure 6 consists of 3 graphs that are not individually labeled; thus it is unclear which graph is being referred to when referencing Figure 6 in the Specification. It is suggested that each graph in Figure 6 be designated a label, such as A, B, and C, as done for Figures 1, 3 and 4. It is suggested that each part of Figure 2 is also further labeled A and B. The corrected drawings/figures are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings/figures will not be held in abeyance.
Appropriate corrections are 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 1-19 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.
Claim 1, part a, recites “a first threshold value” and “a second threshold value,” which are confusing terms because the values are not defined. One of ordinary skill in the art would not be able to determine, with a reasonable degree of certainty, how to practice the claimed invention without knowing what are the first and second threshold values. Further, it would be unclear for a skilled artisan to determine, with a reasonable degree of certainty, whether one or both peanut peptides are taken into account in each of the threshold values and/or how to derive or determine these values. Thus the claim language fails to clearly define the metes and bounds of the claimed invention.
Claims 2-19 are rejected for being dependent on claim 1.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a method for determining the risk of anaphylaxis in a subject allergic to peanuts comprising contacting two peanut peptides, SEQ ID NOs:1 and 2, coupled to a solid surface with a biological sample. Allergy associated immunoglobulins, AAI-1 and AAI-2, if present in the subject’s sample, will bind to the peanut peptide moieties and labeled AAI-specific antibodies are detected when they bind to the AAI-peptide-surface complexes. Measuring these binding events enables determination of binding values for each complex and these values are combined and compared to a first and a second threshold value and further used to designate a subject as level 1, 2, or 3 for allergy reactivity. A subject designated as level 1, 2, or 3, will have a specific percent (%) risk for a Cofar grade 3 or higher reaction vs another percent (%) risk for Cofar grade 2 or lower reaction after consuming < 4 mg, < 14 mg, < 44 mg, < 144 mg, < 444 mg, < 1444 mg, and < 4444 mg.
‘An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement."Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).’ See MPEP § 2163.03 subsection V.
The instant claim and Specification disclose determining peptide binding values for each AAI-1-peptide-surface and AAI-2-peptide-surface complex with a specific labeled reagent, combining peptide binding values, and comparing the combined binding value to a first threshold value and a second threshold value (instant Specification, pg. 5, lines 1-9; pg. 22, lines 3-17). However, the claim language and Specification only imply a general result for threshold values and fail to explain how the first and second threshold values are derived and/or measured and whether the threshold values pertain to one peptide or a combined threshold value for both peptides. The claim language and description in the Specification for determining a first and second threshold values fail to sufficiently identify how to achieve the desired result as recited in the instant claim and thus fail to specify the bounds of the first and second threshold values.
Further, the instant claim and Specification disclose that for determining percent (%) risk of severe reaction “[t]here are two main components of the methodology. First, a peanut threshold examination, as described herein, is performed that places the patient into one of three levels of epitope reactivity to epitopes h2.008 (WELQGDRRCQSQLER) and h3.100 (EYDEDEYEYDEEDRR). Levels 1, 2, and 3 are described herein. Second, a severe reaction database is generated. This is a database of patients who have undergone standardized (e.g., PRACTALL) oral food challenges (OFCs) to determine anaphylactic risk. Specifically, the database records at which amount of ingested peanut each patient reached a state of severe reaction and also the results of the peanut threshold test for a particular patient. This allows the determination of the percentage of patients in each Level (1, 2, or 3) reach a severe reaction. Any standardized OFCs database can be used, and indeed, the database can be extended and made more generalizable by incorporating more patient data. (instant Specification, pgs. 62-63 “Example 4”; also see pg. 25, lines 10-25). The instant claim and Specification define a percent (%) risk within a designated level for a Cofar grade severity after consuming a specific amount of allergen, which amounts to a descriptive result. However, the instant claim and Specification fail to explicitly detail and/or identify the exact publicly available/accessible oral food challenge data using PRACTALL dosing, and the exact methodology used to interpret and/or manipulate the specific and exact data/information (eg., what is/are the specific statistical analysis, algorithm(s), hand-calculation(s), etc.) to achieve the desired result as recited in the instant claim.
For the reasons discussed herein above, claim 1 and the Specification fail to sufficiently explain, detail, and or identify how to achieve the desired results for the two threshold levels and percent risk of severe reaction within each designated level per mg of allergen consumed. Thus, the Applicant does not demonstrate, to a person having ordinary skill in the art, that the Applicant is in possession of the claimed invention.
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 1-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to an abstract idea and a law of nature without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101
(see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the
claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e.,
mathematical concepts, certain methods of organizing human activity such as a fundamental
economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application
(see MPEP § 2106.05(a)-(c), (e)-(h)). Only if a claim
(1) recites a judicial exception and
(2) does not integrate that exception into a practical application, do we then look
to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the
claimed judicial exception into a patent-eligible application of the judicial exception.
Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider
whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-
understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A
JUDICIALEXCEPTION
Step 2A, Prong 1
Claim 1 recites “determining a threshold cumulative reactive dose,” which the instant specification clarifies involves (1) determining the sum of all incremental doses leading up to and including the exact dose that triggers the reaction, or allergy symptoms, associated with the exposure to an allergen (instant Specification pg. 3, lines 16-31; pg. 13, lines 27-32- pg. 12, lines 1-32; pg. 13, lines 1-32, and pg. 14, lines 1-8) and (2) determining the binding values of AAI-peptide-solid support complexes for AAI- and AAI-2 (instant Specification pg. 8, lines 21-29; pg. 12, lines 1-32; pg. 13, lines 1-32, and pg. 14, lines 1-8), which is directed to an abstract mental process/mathematical concept, namely a mathematical calculation (sum of all incremental doses). More recent opinions of the Supreme Court have affirmatively characterized mathematical relationships, calculations, and formulas as abstract ideas. See, e.g., Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 218, 110 USPQ2d 1976, 1981 (2014); Bilski v. Kappos, 561 U.S. 593, 611-12, 95 USPQ2d 1001, 1010 (2010). See MPEP 2106.049(a)(2).
Further, claim 1 recites “to generate a combine peptide binding value,” which involves taking the sum of AAI-1 binding and AAI-2 binding values, is directed to an abstract mental process/mathematical concept, namely a mathematical calculation.
Further, claim 1 recites several comparisons between the combined binding values and first and second threshold values to determine if combined binding value is lesser, equal to, or greater than the threshold values and to determine if the cumulative reactive dose (CRD) is lesser, equal to, or greater than a peanut protein amount, which is all directed to an abstract idea, namely an abstract mental process. In re Killian (Fed. Cir. 2022 / PTAB), the Federal Circuit and PTAB found claims directed to "selecting" individuals eligible for SSDI benefits and "determining" if they were qualified was abstract. The courts held that comprehending and comparing information in this manner is fundamentally a mental process, and performing it on a computer does not confer patentability. Further, '[t]he courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’" (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same). Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions.' See MPEP 2106.049(a)(2).
Further, claim 1 recites, several times, a correlation between (1) level of combined peptide binding value relative to first and second threshold values, determined upon complex formation with naturally generated allergy associated immunoglobulins present in a subjects biological sample after exposure to peanut, a natural allergen; (2) designated epitope reactivity level, where reactivity to an allergen is a natural phenomenon; (3) a Cofar grade, which defines a subject’s medical state or severity of a natural immune reaction after exposure to a natural allergen, and (4) mg amounts of peanut, a natural allergen, consumed. This observed natural correlation/relationship between (1), (2), (3) and (4), defined herein above, is directed to a law of nature, namely a natural phenomenon.
Further, claim 1, part b, recites percent (%) risk for Cofar grade 3 or above and Cofar grade 2 or below. Though the claim language and specification fail to describe/detail the methodology used to interpret and/or manipulate the data used to arrive at the recited percents, percentage represents a type of ratio compared to 100, which is directed to an abstract idea or a mathematical concept.
Further, claim 1, part a, recites “determining a threshold cumulative reactive dose,” and the Specification clarify that cumulative reactive dose (CRD) is a “cumulative sum of the amounts of allergen administered to a subject (instant Specification, pg. 3, lines 21-24).” Thus determining a threshold CRD is directed to an abstract idea/abstract mental process, namely a mathematical calculation, even if it is performed using a computer. the Federal Circuit has explained, “[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent-ineligible invention could be performed via pen and paper or in a person’s mind.” Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 SPQ2d 1681, 1702 (Fed. Cir. 2015). See also Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1318, 120 USPQ2d 1353, 1360 (Fed. Cir. 2016) (‘‘[W]ith the exception of generic computer-implemented steps, there is nothing in the claims themselves that foreclose them from being performed by a human, mentally or with pen and paper.’’); Mortgage Grader, Inc. v. First Choice Loan Servs. Inc., 811 F.3d 1314, 1324, 117 USPQ2d 1693, 1699 (Fed. Cir. 2016) (holding that computer-implemented method for "anonymous loan shopping" was an abstract idea because it could be "performed by humans without a computer")”. See MPEP 2106.04.(a)(2).
Step 2A, Prong 2
The judicial exceptions are not integrated into a practical application because the additional elements of (1) contacting peanut peptides having amino acid sequences SEQ ID NOs: 1 and 2, respectively, to at least one solid surface (claim 1); (2) contacting AAI-1- and AAI-2-peptide solid support complexes with at least one labeling reagent (claim 1); and (3) measuring binding of at least one labeling reagent to the AAI-1- and AAI-2- peptide solid support complexes (claims 1 and 17-18) are insignificant extra-solution activities, namely data-gathering steps, that do not add meaningful limitations to the judicial exception.
Further, the judicial exceptions are not integrated into a practical application because the additional elements of “first amount of a peanut protein is about 300 mg or about 444 mg of a peanut protein (claim 2),” “second amount of a peanut protein [is] about 1000 mg or about 1444 mg of a peanut protein (claim 3),” the first and second biological sample are derived from the same biological sample (claim 4), “first peanut peptide comprises the amino acid sequence according to SEQ ID NO:1 (claim 5),” and “second peanut peptide comprises the amino acid sequence according to SEQ ID NO:2 (claim 6)” are insignificant extra-solution activities, namely data-gathering steps or preliminary steps that are incidental to observing the result or natural correlation (phenomenon)/law of nature and performing the abstract mental process that do not add any meaningful limitations to integrate the judicial exceptions into a practical application.
Further, the judicial exceptions are not integrated into a practical application because the additional elements comprising assay components “first solid support…[and] second solid support…comprise[]…microsphere…glass array…silicone array…membrane….or microtiter plate (claims 7-9),” AAI-1 and AAI-2 each “comprise[] at least one first IgG and/or at least one first IgE (claims 10-11),” and labeling reagent(s) for AAI-1 and AAI-2 comprise “detectably labeled anti-human antibody (claims 12-13)” with the same chemical structure (claim 16) and each with a fluorophore (claims 14-15) are insignificant extra-solution activities, namely data-gathering steps or pre-solution activities that are tangential to observing the result or natural correlation (phenomenon)/law of nature and performing the abstract mental process.
ELIGIBILITY STEP 2B: WHETHER ADDITIONAL ELEMENTS AMOUNT TO
SIGNIFICANTLY MORE THAN THE JUDICIAL EXCEPTION (INVENTIVE CONCEPT)
Step 2B
The instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because the methods/techniques for determining a threshold cumulative reactive dose, which involves measuring (detecting) binding and determining binding values (quantifying), using flow cytometry assay, multiplex peptide-bead flow cytometric analysis device, lateral flow assay device, lateral flow immunoassay, or immunoassay comprising a solid support carried out by a point of care device (claims 17-19, instant Specification pg. 17, lines 15-32 and pgs. 18-20), which are well-known, routine, and conventional in the art. For instance, throughout the review of the state of art at the time of filing, in a review summarizing known techniques in the art, Dincer teaches multiplexed point-of-care technologies for the purposes of detecting and quantifying two or more target analytes simultaneously, such as flow cytometry assays (including those provided by Luminex®), multiplexed bead-based flow cytometry assay, and multiplexed lateral flow assay and devices (Dincer et al., Multiplexed Point-of-Care Testing-xPOCT, 2017, Trends in Biotechnology, 35, 8, pg. 728, Abstract; pg. 729, Fig. 1; pg. 730, “Paper-Based Systems”; and pg. 734, full paras 1-2).
In the instant claim, the additional element of determining a cumulative reactive dose (CRD), which is directed to an abstract idea, is not sufficient to amount to significantly more than the judicial exceptions. For instance, the Specification discloses an algorithm, which is directed to a mathematical formula or equation, may be used to predict the cumulative reactive dose [CRD] (instant Specification pg. 43, lines 19-22 and pg. 45). However, the tool (eg., a computer) used to execute the algorithm by receiving inputs and displaying results does not transform the algorithm into an unconventional solution that improves the functioning of the tool, a technology, and/or a process.
For these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception.
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.
Claim(s) 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Getts et al., (PG Pub. No.: US 2019/0359660 A1, Pub. Date: 11/28/2019, provided in IDS filed on 06/19/2024 as U.S. Patent App. Cite No. 1), in view of Dreskin et al., (PG Pub. No.: US 2014/0080730 A1, Pub. Date: 03/20/2014), Goodwin, (J. Goodwin, Test: Shows How Much Peanut an Allergic Child can Tolerate, 23 September 2022, Allergic Living, URL: https://www. allergicliving.com/2022/09/23/test-shows-how-much-peanut-an-allergic-child-can-tolerate/), and Bird et al., (Bird et al., Conducting an Oral Food Challenge: An Update to the 2009 Adverse Reactions to Foods Committee Work Group Report, 2020, J Allergy Clin Immunol Pract, 8, 75-90), as evidenced by Chinthrajah et al., (Chinthrajah et al., Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy, 2022, J Allergy Clin Immunol., 149, 6, pgs. 2166–2170).
Throughout the disclosure, Getts teaches peptide biomarkers containing allergenic epitopes and methods and kits employing these for diagnosing an allergy, monitoring development of tolerance in an allergic subject, determining development of tolerance or outgrowing the allergy over time, detecting an increase in allergic intensity/adverse event during treatment, and sensitizing an infant to one or more peanut allergens to induce tolerance. Getts teaches several embodiments including one embodiment related to methods using a plurality, meaning two or more, epitope-containing peptides. In some embodiments, methods comprise conjugating each peptide to one or separate solid supports, which may include a microsphere bead, glass array, silicone array, membrane, or microtiter plate. Getts further teaches contacting the immobilized epitope-containing peptides with serum from a subject under conditions enabling one or more allergy-associated immunoglobulins (AAI) present in the serum to bind the immobilized peptides. Getts further teaches detecting the binding of an AAI-specific labeling reagent to an AAI-peptide-solid support complex. Getts teaches combined detected amounts of two or more AAI below or above a threshold indicates if a subject is allergic or not allergic.
Regarding claim 1, Getts teaches a method comprising a) determining a threshold cumulative reactive dose of a peanut peptide for the subject comprising: contacting at least one first peanut peptide comprising the amino acid sequence WELQGDRRCQSQLER (SEQ ID NO:1), or an amino acid sequence comprising SEQ ID NO:1 but having one to four conservative amino acid substitutions therein (US 2019/0359660 A1: paras 0037, 0041, 0051-0052; paras 0115- 0117, ref. SEQ ID NO: 39, 100% seq identity with SEQ ID NO:1 in instant claim), coupled to at least one first solid support with at least one first biological sample obtained from the subject (US 2019/0359660 A1: paras 0037, 0042, 0045, 0183) wherein the contacting is under conditions sufficient to permit binding of at least one allergy associated immunoglobulin (AAI-1) present in the at least one first biological sample to the at least one first peanut peptide to form at least one AAI-1-peptide-solid support complex (US 2019/0359660 A1: paras 0008-0010); contacting at least one second peanut peptide comprising the amino acid sequence EYDEDEYEYDEEDRR (SEQ ID N0:2), or an amino acid sequence comprising SEQ ID NO:2 but having one to four conservative amino acid substitutions therein (US 2019/0359660 A1: paras 0037, 0099, 0115, 0117, ref. SEQ ID NO: 64, 100% seq identity with SEQ ID NO:2 in instant claim;; paras 0008-0010, 0057), coupled to at least one second solid support with at least one second biological sample obtained from the subject (US 2019/0359660 A1: paras 0057-0058), wherein the contacting is under conditions sufficient to permit binding of at least one second allergy associated immunoglobulin (AAI-2) present in the at least one second biological sample to the at least one second peanut peptide to form at least one AAI-2-peptide-solid support complex (US 2019/0359660 A1: paras 0008-0010, 0057, 0183, 0188-0189); contacting the at least one AAI-1-peptide-solid support complex with at least one AAI-1-specific labeling reagent under conditions sufficient to permit binding of the at least one AAI-1 specific labeling reagent to the at least one AAI-1-peptide- solid support complex (US 2019/0359660 A1: paras 0008-0010); measuring the binding of the at least one AAI-1-specific labeling reagent to the at least one AAI-1-peptide-solid support complex, thereby determining at least one AAI-1-peptide binding value (US 2019/0359660 A1: paras 0008-0010, 0064, 0067-0068, and 0095); contacting the at least one AAI-2-peptide-solid support complex with at least one AAI-2-specific labeling reagent under conditions sufficient to permit binding of the at least one AAI-2 specific labeling reagent to the at least one AAI-2-peptide- solid support complex (US 2019/0359660 A1: paras 0008-0010); measuring the binding of the at least one AAI-2-specific labeling reagent to the at least one AAI-2-peptide-solid support complex, thereby determining at least one AAI-2-peptide binding value (US 2019/0359660 A1: 0008-0010 and 0064); Getts teaches a first and second threshold value (US 2019/0359660 A1: paras 0146 and 0168-0169); Getts teaches determination whether a subject’s combined peptide binding value is above or below a first and second threshold value indicates if the subject is or is not allergic to peanuts (Getts et al., US 2019/0359660 A1: paras 0042, 0051, and 0146). Getts does not explicitly teach determining the risk of anaphylaxis and Getts does not teach designating a subject as reactivity level 1, 2, or 3 to describe percent risk for allergic reaction severity per mg amounts of peanut consumed using the Cofar grading scale.
Throughout the disclosure, Dreskin teaches methods for determining likelihood (risk) of a degree of allergic reaction or severity of an allergic reaction using a threshold value instead of binding activity. Dreskin teaches the threshold value of binding is related to the binding between immunoglobulins (IgE) and the amino acid sequence of epitope-containing peptides. Dreskin further teaches that the level of binding activity of IgE present in a subject’s sample to the epitope-containing peptides is indicative of subject’s severity of allergic reaction to peanuts. Dreskin teaches another embodiment of the invention related to methods for predicting likelihood of a subject’s desensitization to allergic reaction to peanuts. Dreskin teaches the level of binding between IgE present in subject’s sample to the amino acid sequence of the epitope-containing peptides is indicative of likelihood of desensitization. Dreskin teaches that level of binding is determined by comparing binding activity (value) to a threshold value to determine if binding activity is above or below the threshold value. Dreskin further teaches the threshold value can be a published value or can be determined by analyzing the binding activity from a control group and a preset value determined experimentally. Dreskin teaches classifying subjects by allergy severity using a grading scale, established by the World Health Organization (WHO) and referred to as Cofar: grade I, cutaneous symptoms alone ( angioedema, rash, hives); grade II, two organ system involvement ( e.g. lower respiratory and cutaneous, or gastrointestinal and lower respiratory); grade III, three or more organ system involvement and/or those with upper respiratory involvement (upper respiratory angioedema, stridor); grade IV, cardiovascular compromise (shock, decrease pulse, syncope).
Dreskin teaches determining a likelihood (risk) of a degree of allergic reaction severity of a subject to peanuts using a threshold value of binding between AAI and peanut peptides (US 2014/0080730 A1: Abstract; paras 0003, 0025, 0029, 0034, 0037) when the at least one AAI-1 peptide binding value is less than or great than the first threshold value (US 2014/0080730 A1: paras 0034-0038, 0075). Getts and Dreskin do not teach designating level of reactivity, percent (%) risk of Cofar grade based on mg of peanut consumed, or cumulative peanut doses of ≤ 4 mg, ≤ 14 mg, ≤ 44 mg, ≤ 144 mg, ≤ 444 mg, ≤ 1444 mg, and ≤ 4444 mg.
Throughout the article, Goodwin teaches epitope testing, which provides reaction thresholds, by detecting binding to, or levels of, two peanut protein present in a patient’s sample is more reliable for diagnosing peanut allergy than traditional skin or blood testing. Goodwin teaches that the art teaches AAI binding to a variety of peanut protein epitopes indicates likelihood (risk) of severe allergic reaction. Goodwin teaches epitope profiling by detecting binding to or levels of two peanut protein epitopes combined with data from placebo-controlled oral food challenges (OFC) that used PRACTALL dosing can be used to predict how much peanut a patient could eat before developing an adverse reaction and then grouping patents into one of three levels of reactivity. Goodwin further teaches that on average a subject designated level 3, part of the high tolerant group, is four times more likely to tolerate a specific dose of peanut relative to subject designated level 1, as part of low tolerant group.
Goodwin teaches epitope testing to determine tolerated doses of peanut and designating subjects to one of three levels of peanut protein epitope reactivity. Goodwin teaches level 1 (low tolerance group) is the high/most reactive to the lowest amount of peanut, wherein 92% is likely to tolerate 4 mg of peanut and 8% is likely to have some reaction, 77% is likely to tolerate 14 mg of peanut and 23% is likely to have some reaction, 53% can tolerate 44 mg of peanuts and 47% would have some reaction, and 29% can tolerate 144 mg of peanuts. Level 2 (moderate group) is moderately reactive, wherein 65% has a likelihood of tolerating 144 mg and 36% is likelihood of tolerating 444 mg of peanuts. Level 3 (high tolerance group) is the low/least reactive since subjects react to higher amounts of peanut and not the lower amounts of peanut, and wherein 98% is likely to tolerate 4 mg, 95% is likely to tolerate 14 mg, 94% is likely to tolerate 44 mg, 88% is likely to tolerate 144 mg and 73% can tolerate more than 444 mg of peanut. Goodwin does not teach additional cumulative doses of 1444 mg and 4444 mg of peanut consumed or a grading scale for allergy severity, or Cofar grades.
Throughout the report, Bird teaches safety guidelines; treatment of IgE-mediated allergic reactions; infant and adult challenges; psychological consideration for participants and their families; and guidance for baked milk or baked egg challenges, masking agents, and blinding recipes for common food allergies. Bird teaches the PRACTALL dosing protocol, which are well-known, routine, and conventional guidelines used in the art when performing oral food challenges (OFCs). Bird further teaches recommendations for conducting and interpreting challenges for patients suspected of having food-protein-induced enterocolitis syndrome. Bird reports patient details including portion sizes, skin test results, and written consents, among other details, in tables and figures.
Bird teaches the highest successfully consumed dose, also referred to as the highest tolerated dose, eliciting dose, or reactive dose, where the challenge is stopped. Bird teaches the well-known and conventional PRACTALL dosing protocol consisting of 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 1000 mg, and 3000 mg of individual peanut doses consumed which equals to cumulative peanut doses of 4 mg, 14 mg, 44 mg, 144 mg, 444 mg, 1444 mg, and 4444 mg of peanuts consumed (Bird et al., 2020, J Allergy Clin Immunol Pract, 8, pg. 86, section “OFCs for Research” and pg. 87, Fig. 2). Bird does not teach the Cofar grading scale for allergy severity.
However, Dreskin, in the same field of endeavor, teaches classifying symptoms following naturally occurring exposure to peanuts into [Cofar] grades of anaphylaxis, as established by the World Health Organization [WHO] (US 2014/0080730 A1: para 0062 and also see Chinthrajah et al., Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy, 2022, J Allergy Clin Immunol., 149, 6, pgs. 2166–2170 *Author Manuscript pgs. 1-13 with emphasis on *Author Manuscript pgs. 10-11, Tables 1-2, WHO Cofar scale).
It would have been prima facie obvious, at the time of filing, to try a finite number of peanut peptide sequences in order to optimize the method comprising a finite number of peanut peptide sequences in order to arrive at two peanut peptides having amino acid sequences of SEQ ID NO:1 and SEQ ID NO:2, as taught by Getts. Getts explicitly teaches peanut peptides with SEQ ID NOs: 1 and 2 as part of the finite number of options for epitopes in an embodiment for detecting binding of labeled reagents binding to a plurality of peanut peptides to diagnose a subject with a peanut allergy (see Getts et al., US 2019/0359660 A1: paras 0042; and 0037, SEQ ID NOs: 39 and 64 represent SEQ ID NOs: 1 and 2, respectively, recited in the instant claim). Further, the prior art also teaches that binding of more than one peanut protein epitope may also indicate severity of peanut allergy (see Goodwin). Thus, a skilled artisan would have been motivated to try the finite number of known peanut peptide sequences (solutions) taught by Getts as part of routine optimization to determine that peptides having sequences SEQ ID NOs: 1 and 2 would be optimal peanut peptide epitopes that would enable diagnosis of peanut allergy and a starting point for determining severity of a peanut allergy. A skilled artisan would have a reasonable expectation of success because Getts teaches and suggests SEQ ID NOs: 1 and 2 as part of a finite number of known solutions that would yield expected and predictable results.
It would have been further prima facie obvious, at the time of filing, to combine the method for diagnosing, monitoring development of tolerance, monitor outgrowing, and detecting increased intensity of an allergic reaction comprising of peanut peptides with amino acid sequences of SEQ ID NO:1 and SEQ ID NO:2, referred to as SEQ ID NO:39 and SEQ ID NO: 64, respectively, in referenced disclosure, as taught by Getts, with the method for determining the likelihood (risk) of a degree of allergic reaction or severity of an allergic reaction, using threshold values, as taught by Dreskin. At the time of filing, the prior art taught that severe allergic reaction to peanut protein accounted for 80% of peanut-allergy related deaths in subjects diagnosed with a peanut allergy (see Dreskin et al., US 2014/0080730 A1: para 0043). As discussed herein above, Getts teaches combining peptide binding values and comparing to two threshold values but does not teach using these results to predict percent risk of anaphylaxis or severe allergic reaction. Getts teaches using binding activity to diagnose, or indicate, a subject has a peanut allergy (Getts et al., US 2019/0359660 A1: para 0042). However, the prior art teaches that subjects with high binding activity between a subjects IgE to peanut protein epitope do not present with a life-threatening allergic reaction. The prior art further teaches that the converse is also true, where subjects with low binding activity to peanut protein epitope may present with a life-threatening allergic reaction. Thus, the prior teaches the binding activity between a subject’s immunoglobulin and peanut protein/peptides does not provide information about degree of severity of a potential allergic reaction by a subject exposed to specific amounts of peanut. Instead, the prior art teaches that using a threshold value, determined by analyzing the binding activity of a subject’s immunoglobulin and a peanut protein/peptide, is a more accurate predictor of, and/or enables a skilled artisan to determine, likelihood (risk) of severity of an allergic reaction by a subject exposed to an allergen (see Dreskin et al., US 2014/0080730 A1: para 0029). Thus, a skilled artisan would have been motivated to combine these teachings such that the methods comprising combined binding values and two threshold binding values taught by Getts would be performed to determine risk of a severe reaction (anaphylaxis) with exposure to peanuts, as taught by Dreskin, because it would enable prediction and/or determination of the likelihood severe allergic reaction to specific amounts of peanut, allowing subjects to avoid exposure/ consumption of life-threatening doses/amounts of peanut. At the time of filing, a skilled artisan would have a reasonable expectation of success for combining the teachings of Getts and Dreskin because this combination would amount to combining known components/elements already taught in the prior art, and known to perform the same function separately as they would when combined, to yield expected and predictable results.
It would have been prima facie obvious, at the time of filing, to combine the teachings of Getts, in view of Dreskin, with the method of assigning patients with a peanut allergy one of three levels of reactivity, as taught by Goodwin. The prior art teaches that peanut allergy is not a binary consisting only of “you react” and “you don’t react.” Instead, patients with a peanut allergy have different thresholds/tolerances or different levels of reactivity to different amounts of peanut proteins (see Goodwin, 2022 August 3, Allergic Living.com, pdf pg. 3). Thus, a skilled artisan would have been motivated to combine Getts, in view of Dreskin, with the teachings of designating subjects into either reactivity level 1, 2, or 3 as taught by Goodwin because it would enable patients that do not react to trace amounts of peanuts, or that have a higher tolerance, and patients with a lower reactivity to avoid exposure or consume safe amounts of peanuts with lower to no risk of a life-threatening reaction and also allows patients to decide if proper oral immunotherapy is a proper treatment for them. At the time of filing, a skilled artisan would have a reasonable expectation of success for combining the teachings of Getts, Dreskin, and Goodwin because this combination would amount to combining known components/elements already taught in the prior art, and known to perform the same function separately as they would when combined, to yield expected and predictable results.
It would have been further prima facie obvious, at the time of filing, to combine the teachings of Getts, Dreskin, Goodwin, with teachings of a (Cofar) grading scale to describe reaction severity, as taught by Dreskin. As discussed herein above, the prior art teaches that subjects diagnosed with a peanut allergy have different thresholds and tolerate different amounts of peanut protein before a serious or life-threatening reaction is triggered. The Cofar grading scale is a standardized system used to measure severity of an allergic reaction. A skilled artisan would have been motivated to combine the teachings of Getts, Dreskin, and Goodwin because it would enable a more precise determination or prediction of risk of a severe allergic reaction, using Cofar grades, that apply to a specific reactivity level for a specific amount of peanut protein, enabling a subject to avoid life-threatening amounts of peanuts, determine safe amounts that can be consumed if any at all, and help curve allergy-related morbidity in peanut-allergic patients. At the time of filing, a skilled artisan would have a reasonable expectation of success for combining the teachings of Getts, Dreskin, and Goodwin because this combination would amount to combining known components/elements already taught in the prior art, and known to perform the same function separately as they would when combined, to yield expected and predictable results.
It would have been further prima facie obvious, at the time of filing, to combine the teachings of Getts, in view of Dreskin, with the percent likelihood to tolerate, or (based on remaining percentage) percent risk of an allergic reaction for, specific mg amounts of peanut consumption for reactivity levels of 1, 2, and 3, as taught by Goodwin. At the time of filing, it was known in the art that about 2% of the US population is allergic to peanuts. The global percentage of peanut allergic people is similarly low. Thus, at the time of filing, for a skilled artisan, it would be obvious and expected that 2% of subjects designated level 1 or 2, corresponding to low or moderate levels of reactivity or to low or moderate tolerance, respectively, would be at risk for an allergic reaction at CoFar grade 3 or above after consuming a low to moderate amount of peanut (see Goodwin). Further, the percentages for likelihood of tolerating (with remaining percentages implied to be risk of having a reaction to) mg amounts of peanut consumed taught by Goodwin are in close agreement and/or overlap with and follow the same trend as percentages for risk of an allergic reaction recited for each reactivity level in the instant claim. Differences between the recited and taught percentages for risks and likelihoods of not tolerating, or tolerating, specific mg amounts of peanut are attributed to variations in the OFC data used, and/or differences in any additional clinical data incorporated, to determine each percentage result since variations between the data will exist because each is based on different subject populations. Further, it would be obvious to a skilled artisan that as a subject allergic to peanuts and designated level 1 (low tolerance, high reactivity) or as level 2 (moderate tolerance and reactivity) would start with a low (2%) risk of having a severe allergic reaction, representative of severe peanut allergy prevalence in the greater population, with the precent risk increasing with increasing mg amounts of peanuts. It would be further obvious to a skilled artisan that a subject designated as level 3 (high tolerance, low reactivity) would have very low to no risk of an allergic reaction at the lowest dose of 4 mg of peanut, with percent risk of an allergic reaction increasing at higher amounts of peanut consumption. At the time of filing, a skilled artisan would have a reasonable expectation of success for combining these teachings because the prior art teaches using peptide binging levels detected in combination with OFC data to designate a subject to a reactivity level of 1 (low tolerance, high reactivity), 2 (moderate), or 3 (high tolerance, low reactivity) and predicting percent risk or likelihood of severity of allergic reaction based on mg amounts of peanut consumed. Using different OFC data that reflects a specific patient population to arrive at the claimed invention would be part of routine optimization, leading to an obvious variation in percentages for risk or likelihood of a reaction for specific amounts of peanuts consumed. A skilled artisan would have been motivated to combine the teachings of Getts, in view of Dreskin, with the teachings of Goodwin because it would enable more precise prediction or determination of likelihood (risk) of degree of severity of an allergic reaction for specific amounts of peanut, enabling a peanut-allergic person to decide between avoidance and safe consumption/exposure especially with regards to treatment and potential exposures during social gatherings/events. A skilled artisan would have a reasonable expectation of success because combining these teachings amounts to combining known components/elements already taught in the prior art, and known to perform the same function separately as they would when combined, to yield expected and predictable results.
It would have been prima facie obvious, at the time of filing, to combine the teachings of Getts, in view of Dreskin and Goodwin, with the semi-logarithmic incremental peanut protein doses according to the PRACTALL dosing protocol, as taught by Bird. A skilled artisan would have been motivated to combine these teachings because it would enable a skilled artisan to determine the specific dose a subject has an objective clinical reaction to. A person having ordinary skill in the art would have a reasonable expectation of success because PRACTALL dosing is a standard dosing protocol that is well-known, routine, and conventional in the art thus would yield expected and predictable results.
Regarding claim 4, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the at least one first biological sample and the at least one second biological sample are derived from the same biological sample (Getts et al., US 2019/0359660 A1: paras 0008-0010).
Regarding claim 5, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the at least one first peanut peptide comprises the amino acid sequence according to SEQ ID NO:1 (US 2019/0359660 A1: paras 0115- 0117, SEQ ID NO: 39, 100% sequence identity), see BLAST results below (full BLAST details provided as NPL).
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Regarding claim 6, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the at least one second peanut peptide comprises the amino acid sequence according to SEQ ID NO:2 (US 2019/0359660 A1: paras 0115-0117, SEQ ID NO: 64, 100% sequence identity), see BLAST results below (full BLAST details provided as NPL).
[AltContent: textbox (SEQ ID NO:2, Instant Application # 18/428,273)][AltContent: textbox (SEQ ID NO:64, Ref. PG Pub. No. US 2019/0359660 A1)]
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[AltContent: textbox (SEQ ID NO:64, Ref. PG Pub. No. US 2019/0359660 A1)]
Regarding claim 7, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the at least one first solid support comprises at least one first microsphere bead, at least one first glass array, at least one first silicone array, at least one first membrane, or at least one first microtiter plate (US 2019/0359660 A1: paras 0053-0054, 0057-0058).
Regarding claim 8, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the at least one second solid support comprises at least one second microsphere bead, at least second one glass array, at least one second silicone array, at least one second membrane, or at least one second microtiter plate (US 2019/0359660 A1: paras 0053-0054, 0057-0058).
Regarding claim 9, Getts, Dreskin, Goodwin, and Bird all the limitations of claims 1 and 4-8. Getts further teaches wherein the at least one first microsphere bead and the at least one second microsphere bead are the same microsphere bead, the at least first one glass array and the at least second one glass array, the at least one first silicone array and the at least one second silicone array are the same silicone array, the at least one first membrane and the at least one second membrane are the same membrane, or the at least one first microtiter plate and the at least one second microtiter plate are the same microtiter plate (US 2019/0359660 A1: para 0057).
Regarding claim 10, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the AAI-1 comprises at least one first IgG and/or at least one first IgE (US 2019/0359660 A1: para 0055).
Regarding claim 11, Getts, Dreskin, Bird, and Goodwin teach all the limitations of claim 1. Getts further teaches wherein the at least one AAI-1-specific labeling reagent comprises at least one first detectably labeled anti-human antibody (US 2019/0359660 A1: para 0055-0057).
Regarding claim 12, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the AAI-2 comprises at least one IgG and/or at least one IgE (US 2019/0359660 A1: para 0055-0057).
Regarding claim 13, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts further teaches wherein the at least one AAI-2-specific labeling reagent comprises at least one second detectably labeled anti-human antibody (US 2019/0359660 A1: para 0055-0057).
Regarding claim 14, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claims 1 and 4-12. Getts further teaches the limitation(s) of claim 12 and wherein the detectable label of the at least one first detectably labeled anti-human antibody comprises at least one first fluorophore (US 2019/0359660 A1: paras 0056).
Regarding claim 15, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claims 1 and 4-13. Getts further teaches the limitation(s) of claim 13 and wherein the detectable label of the at least one second detectably labeled anti-human antibody comprises at least one second fluorophore (US 2019/0359660 A1: paras 0056-0057).
Regarding claim 16, Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1 and 4-15. Getts further teaches the limitation(s) of claim 15 and wherein the at least one first detectably labeled anti-human antibody and the at least one second detectably labeled anti-human antibody have the same chemical structure (US 2019/0359660 A1: para 0055, single labeling reagent used for universal detection of all complexes; and para 0057, multiplexing).
Claim(s) 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Getts et al., (PG Pub. No.: US 2019/0359660 A1, Pub. Date: 11/28/2019, provided in IDS filed on 06/19/2024), in view of Dreskin et al., (PG Pub. No.: US 2014/0080730 A1, Pub. Date: 03/20/2014), Goodwin, (J. Goodwin, Test: Shows How Much Peanut an Allergic Child can Tolerate, 23 September 2022, Living Allergic, URL: https://www. allergicliving.com/ 2022/09/23/test-shows-how-much-peanut-an-allergic-child-can-tolerate/), and Bird et al., (Bird et al., Conducting an Oral Food Challenge: An Update to the 2009 Adverse Reactions to Foods Committee Work Group Report, 2020, J Allergy Clin Immunol Pract, 8, 75-90), as applied to claim 1, and further in view of Inamdar et al., (Inamdar et al., Approaches to maintenance dosing during oral immunotherapy, 2022, J Food Allergy, 4, 98–101).
Regarding claims 2-3, the teachings of Getts, Dreskin, Bird, and Goodwin are discussed herein above. Getts, Dreskin, Goodwin, Bird teach all the limitations of claim 1. Getts, Dreskin, Goodwin, Bird do not teach about 300 mg or about 444 mg as the first amount of peanut and do not teach about 1000 mg or about 1444 mg as a second amount of peanut.
Throughout the article, Inamdar teaches that some long-term studies suggest low daily doses of peanut is associated with tolerating higher doses in food challenges over the long term. Inamdar teaches higher maintenance doses of peanut may protect for longer avoidance intervals and may confer greater tolerance for the allergen.
Inamdar teaches wherein the first amount of a peanut protein is about 300 mg of peanut protein (Inamdar et al., 2022, (J Food Allergy, 4, pg. 100, left col, top half). Inamdar does not explicitly teach a second dose of peanut protein is 1000 mg, but Inamdar teaches 85% of a cohort in a double-blind placebo-controlled food challenge who tolerated 300 mg of peanut protein for 56 weeks were able to tolerate 1000 mg peanut. Thus, using the broadest reasonable interpretation, a person having ordinary skill in the art would reasonably use 1000 mg of peanut protein as the second amount.
It would have been prima facie obvious, at the time of filing, to combine the teachings of Getts, in view of Dreskin, Goodwin, and Bird, with the teachings of 300 mg and 1000 mg as a first and second amount of peanut, as taught by Inamdar. The prior teaches a method of using about 300 mg and about 1000 mg as known amounts to determine a patient’s dose tolerance and to determine if a high tolerance has been achieved after daily low doses for a period of time, which is an obvious variation for the method of using 300 mg and 1000 mg as first and second amounts to determine whether a subject’s level of reactivity or tolerance level is low, moderate, or high. A skilled artisan would have been motivated to combine these teachings because using 300 mg and 1000 mg as the first and second amounts of peanut would enable a skilled artisan to rule out false negative (non-reactive) results, better distinguish between low and high reactivity, and determine a true high reactivity vs non-reactive for a subject allergic to peanuts (see Bird et al., 2020, J Allergy Clin Immunol Pract, 8, pg. 81 At the time of filing, a skilled artisan would have a reasonable expectation of success for combining these teachings because this combination would amount to combining known components/elements already taught in the prior to yield expected and predictable results.
Claims 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Getts et al., (PG Pub. No.: US 2019/0359660 A1, Pub. Date: 11/28/2019, provided in IDS filed on 06/19/2024 as U.S. Patent App. Cite No. 1), in view of Dreskin et al., (PG Pub. No.: US 2014/0080730 A1, Pub. Date: 03/20/2014), Goodwin, (J. Goodwin, Test: Shows How Much Peanut an Allergic Child can Tolerate, 23 September 2022, Allergic Living, URL: https://www. allergicliving.com/2022/09/23/test-shows-how-much-peanut-an-allergic-child-can-tolerate/), and Bird et al., (Bird et al., Conducting an Oral Food Challenge: An Update to the 2009 Adverse Reactions to Foods Committee Work Group Report, 2020, J Allergy Clin Immunol Pract, 8, 75-90), as applied to claim 1, and further in view of Wang et al., (Wang et al., Tetra-primer ARMS-PCR combined with dual color fluorescent lateral flow assay for the discrimination of SARS-CoV-2 and its mutations with a handheld wireless reader, 2022, Lab Chip, 22, 1531-1541).
Regarding claims 17-19, the teachings of Getts, Dreskin, Goodwin, and Bird are discussed herein above. Getts, Dreskin, Goodwin, and Bird teach all the limitations of claim 1. Getts, Dreskin, Bird, and Goodwin do not teach the method of claim 1 carried out by one point of care device.
Throughout the article, Wang teaches a handheld wireless device for quantitative fluorescence signal detection. Wang teaches this handheld device is based on a dual-color quantum dot nanobeads (QBs)-based fluorescent lateral flow assay (LFA). Wang teaches the lateral flow test strip is composed of a sample pad, conjugate pad, nitrocellulose membrane, and absorbent pad. Wang teaches the test strip has Bio-BSA and goat polyclonal anti-mouse IgG antibody immobilized on the control line. Wang further teaches the test strip has two test lines for detection and quantification of two different target analytes with antibody 1 immobilized on test line 1 with specificity for target analyte 1 and antibody 2 immobilized on test line 2 with specificity for target analyte 2.
Wang teaches wherein the measuring of the binding of the at least one first AAI-1-specific labeling reagent to the at least one AAI-1-peptide-solid support complex is carried out by at least one first point of care device (claim 17) and wherein the measuring of the binding of the at least one AAI-2-specific labeling reagent to the at least one AAI-2-peptide-solid support complex is carried out by at least one second point of care device (claim 18) and wherein the at least one first point of care device and at least one second point of care device are the same point of care device (claim 19) [Wang et al., 2022, Lab Chip, 22, pgs. 1533-1535; pg. 1534, Fig. 1b-c].
It would have been prima facie obvious, at the time of filing, to combine the teachings of Getts, in view of Dreskin, Goodwin, and Bird, with the point-of-care device taught by Wang. A skilled artisan would have been motivated to combine these teachings to perform the method of claim 1 using a point-of-care device because it would enable development of a rapid, simple, accurate, and affordable approach for predicting severity to peanut allergy or determining risk of anaphylaxis at the bedside. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known components/elements, known to function the same separately as they do when combined, to yield expected and predictable results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Instant claims 1, 5-6, 10, 12, and 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-8, 12-13, 19-20, 25-28, 31-32, and 36-37 of copending Application No. 18/168. 853 in view Dreskin et al., (PG Pub. No.: US 2014/0080730 A1, Pub. Date: 03/20/2014), Goodwin, (J. Goodwin, Test: Shows How Much Peanut an Allergic Child can Tolerate, 23 September 2022, Allergic Living, URL: https://www. allergicliving.com/2022/09/23/test-shows-how-much-peanut-an-allergic-child-can-tolerate/), and Bird et al., (Bird et al., Conducting an Oral Food Challenge: An Update to the 2009 Adverse Reactions to Foods Committee Work Group Report, 2020, J Allergy Clin Immunol Pract, 8, 75-90).
Reference claims 1, 7-8, 12-13, 19-20, 25-28, 31-32, and 36-37 of copending application 853’ recite all the limitations of instant claims 1, 5-6, 10, 12, and 17-18 but does not explicitly teach determining the risk of anaphylaxis and does not teach designating subjects to one of three levels of reactivity; percent (%) risk of Cofar grade based on mg of peanut consumed for each level of reactivity; or cumulative peanut doses of 4 mg, 14 mg, 44 mg, 144 mg, 444 mg, < 1444 mg, and 4444 mg.
The teachings of Dreskin are discussed herein above. Dreskin teaches determining a likelihood (risk) of a degree of allergic reaction severity of a subject to peanuts using a threshold value of binding between AAI and peanut peptides (US 2014/0080730 A1: Abstract; paras 0003, 0025, 0029, 0034, 0037) when the at least one AAI-1 peptide binding value is less than or great than the first threshold value (US 2014/0080730 A1: paras 0034-0038, 0075). Dreskin do not teach designating level of reactivity, percent (%) risk of Cofar grade based on mg of peanut consumed, or cumulative peanut doses of 4 mg, 14 mg, 44 mg, 144 mg, 444 mg, < 1444 mg, and 4444 mg for each level of reactivity.
The teachings of Goodwin are discussed herein above. Goodwin teaches epitope testing to determine tolerated doses of peanut and designating subjects to one of three levels of peanut protein epitope reactivity. Goodwin teaches level 1 (low tolerance group) is the high/most reactive to the lowest amount of peanut, wherein 92% is likely to tolerate 4 mg of peanut and 8% is likely to have some reaction, 77% is likely to tolerate 14 mg of peanut and 23% is likely to have some reaction, 53% can tolerate 44 mg of peanuts and 47% would have some reaction, and 29% can tolerate 144 mg of peanuts. Level 2 (moderate group) is moderately reactive, wherein 65% has a likelihood of tolerating 144 mg and 36% is likelihood of tolerating 444 mg of peanuts. Level 3 (high tolerance group) is the low/least reactive since subjects react to higher amounts of peanut and not the lower amounts of peanut, and wherein 98% is likely to tolerate 4 mg, 95% is likely to tolerate 14 mg, 94% is likely to tolerate 44 mg, 88% is likely to tolerate 144 mg and 73% can tolerate more than 444 mg of peanut. Goodwin does not teach additional cumulative doses of 1444 mg and 4444 mg of peanut consumed or a grading scale for allergy severity, Cofar grades.
The teachings of Bird are discussed herein above. Bird teaches the highest successfully consumed dose, also referred to as the highest tolerated dose, eliciting dose, or reactive dose, where the challenge is stopped. Bird teaches the well-known and conventional PRACTALL dosing protocol consisting of 1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 300 mg, 1000 mg, and 3000 mg of individual peanut doses consumed which equals to cumulative peanut doses of 4 mg, 14 mg, 44 mg, 144 mg, 444 mg, 1444 mg, and 4444 mg of peanuts consumed (Bird et al., 2020, J Allergy Clin Immunol Pract, 8, pg. 86, section “OFCs for Research” and pg. 87, Fig. 2). Bird does not teach the Cofar grading scale for allergy severity.
Dreskin, in the same field of endeavor, teaches classifying symptoms following naturally occurring exposure to peanuts into [Cofar] grades of anaphylaxis, as established by the World Health Organization [WHO] (US 2014/0080730 A1: para 0062).
The limitations of reference claims 1, 7-8, 12-13, 19-20, 25-28, 31-32, and 36-37 of copending application 853’ is an obvious variation of the claimed invention as recited in instant claims 1, 5-6, 10, 12, and 17-18 because it would have been prima facie obvious to combine reference claims of co-pending 853’ with the teachings of Dreskin, Goodwin, and Bird. As discussed herein above, at the time of filing, the prior art taught that severe allergic reaction to peanut protein accounted for 80% of peanut-allergy related deaths in subjects diagnosed with a peanut allergy (see Dreskin et al., US 2014/0080730 A1: para 0043). Thus, as discussed herein above, a skilled artisan would have been motivated to combine these teaches because for patients diagnosed with a peanut allergy but different tolerance it would enable a more accurate prediction and/or determination of the likelihood (risk) of severe allergic reaction to specific amounts of peanut, based on designated reactivity level and % risk for Cofar grades, allowing peanut-allergic individuals to avoid exposure or safely consume specific amounts of peanut, determined by PRACTALL dosing, with little to no risk of suffering a life-threatening reaction, helping curve allergy-related morbidity in the peanut-allergic population. A skilled artisan would have a reasonable expectation of success because combining these teachings amounts to combining known elements/methods, with each element/method performing the same function or performed in the same manner separately as they do when combined, to yield predictable results.
Conclusion
All examined claims (1-19) are rejected. No claims are allowed.
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/MELISSA LIZETTE LIRIANO-NG/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 June 27, 2026
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