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 .
Election/Restrictions
Applicant’s election of claims 8-18 in the reply filed on 1/16/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of Claims
The amendment filed on 1/16/2026 amended claim 1. Claims 1-18 are pending. Claims 1-7 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/16/2026. Claims 8-18 will be examined on the merits.
Priority
Provisional application 63/478,080, filed on 12/30/2022, is acknowledged.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Claim 12 and dependent claim 13 are being interpreted under 35 U.S.C. 112(f). Claim 12 is drawn to “the kit of claim 8, further comprising a detection means for the detectable antibody,” and claim 13 is drawn to “the kit of claim 12, wherein the detection means [is] colorimetric.” The broadest reasonable interpretation of these claims is any technique capable of detecting the presence of an antibody, and for claim 13, any colorimetric technique for detecting the presence of an antibody. The specification discloses in paragraph [0060] “in examples of kit embodiments, the detectable antibody is… HRP-conjugated and the detection means is 3,3',5,5'-tetramethyl benzidine.” Furthermore, in example 2, paragraph [0189-0190], the specification discloses the use of an anti-human IgG HRP conjugated antibody, and paragraph [0193] discloses that the detection means is TMB. Therefore, for purposes of examination, the examiner will be interpreting “detection means for detecting” as HRP/TMB or functional equivalents in the art.
Claim Objections
Claim 13 is objected to because of the following informalities: claim 13 “wherein the detection means in colorimetric.” Examiner believes claim 13 should read “wherein the detection means is colorimetric.” Appropriate correction is required. If Applicant disagrees, the claim should still be corrected, as “in colorimetric” does not appropriately modify the ‘detection means’.
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 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 14 is dependent from claim 8, which discloses a kit, or a product. Claim 14 then states “the kit of claim 8, wherein the detectable antibody is amplified by a fluorometric reagent” which recites a method step using the verb ‘amplified’. It is unclear if claim 14 is referring to a product or a method. A method step cannot be included in a kit, which is a product. Appropriate correction is required.
Claim 15 is dependent from claim 8, which discloses a kit comprising a capture reagent that is a peptide, and a detection reagent that is a detectable anti-human IgG antibody. Claim 15 recites “the kit of claim 8, wherein the detectable antibody is HRP-conjugated and the detection reagent is 3,3',5,5'-tetramethyl benzidine”. It is unclear if the detection reagent of claim 15 is the detectable antibody recited in claim 15, as according to claim 8, or the 3,3’,5,5’-tetramethyl benzidine as recited in claim 15. Neither claim 15 nor claim 8 recite more than one detection reagent. Appropriate correction is required.
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 8, 9, and 12-18 are rejected under 35 U.S.C. 101 in view of Cox et al., Immunoassay Methods, 2012 May 1 [Updated 2019 Jul 8] (hereinafter Cox), because the claimed invention is directed to a product of nature without significantly more. The claims recite a kit comprising a peptide and a detectable solid support, and anti-transketolase antibody. These claims are directed to a judicial exception of a natural product. This judicial exception is not integrated into a practical application because no method is recited. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the peptide, monoclonal goat anti-human IgG antibo
The following analysis is laid out in accordance with MPEP 2106:
Step 1: Is the Claim directed to a process, machine, article of manufacture, or composition of matter?
Yes – the claims are directed to a composition of matter.
Step 2A: Is the claim directed to a law of nature, natural phenomenon, natural product, or an abstract idea?
Yes – the claims are directed to a natural product.
2A prong 1: Does the claim recite an abstract idea, law of nature, or natural phenomenon (natural product)?
Yes – the claims recite a peptide made by Mycobacterium tuberculosis with no claimed variation to its natural sequence, and a detectable antibody that binds to human IgG.
2A prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No – the claims do not recite any method steps for practical application.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. The claims list the following elements:
Claim 8 recites a kit with a peptide comprising the sequence of SEQ ID NO: 1, 12, 3 or 5, wherein the peptide forms a complex with an anti-transketolase antibody in the biological sample; and as detection reagent, a detectable anti-human IgG antibody, wherein the detectable anti- human IgG antibody binds to anti-transketolase antibody in the complex. The peptide disclosed by claim 8 is part of a sequence to a protein expressed by the organism Mycobacterium tuberculosis (Mtb) without significant modification. This is a naturally occurring product. Anti-human IgG antibodies are naturally occurring as well; additionally, anti-human IgG antibodies are known in the art to be a common detection reagent for human IgG (See Cox, pg 8, last paragraph, lines 4-7). Thus, adding the detectable anti-human IgG antibody of claim 8 to the kit of claim 8 does not amount to significantly more than the naturally occurring peptide in regard to the inventive concept of claim 8.
Claim 9 is drawn to the kit of claim 8, further comprising a solid support. This support does not add any meaningful limitations that would draw the claims to significantly more than the natural products recited in claim 8 because solid supports are routinely added to immunoassay kits (see Cox, pg 3, “Basic Steps for Developing and Running an Immunoassay”). This indicates that use of a solid support is well known, routine, and conventional in the art (see MPEP 2106.05(d)). Therefore, claim 9 is not drawn to more than the natural product of claim 8.
Claim 12 is drawn to the kit of claim 8, further comprising a detection means for the detectable antibody, and claim 13 specifies this detection means is colorimetric. As interpreted under 112(f) above, the detection means is HRP/TMB, which mediate a colorimetric reaction. This detection means is also disclosed in claim 15. The use of HRP/TMB is well-known, routine, and conventional in the art of immunoassays (see Cox, pg 5, “Enzymes and Substrates”). Therefore, claims 12, 13, and 15 are not drawn to significantly more than the natural product of claim 8.
Claim 14 is drawn to a fluorometric reagent to amplify the detectable antibody. Fluorometric reagents are well-known, routine, and conventional in the art of immunoassays (see Cox, pg 5, “Enzymes and Substrates”). Therefore, claim 14 is not drawn to significantly more than the natural product of claim 8.
Claim 16 is drawn to the detectable antibody as a monoclonal antibody, and claim 17 further limits this to a goat monoclonal antibody. Monoclonal antibodies are well-known, routine, and conventional in the art of immunoassays, and the use of goats to derive these monoclonal antibodies is also well-known, routine, and conventional in the art of antibody preparation (see Cox pg 8, first paragraph, lines 6-9, and last paragraph, lines 4-7). Therefore, claims 16 and 17 are not drawn to significantly more than the natural product of claim 8.
Finally, claim 18 is drawn to the use of an anti-transketolase antibody as a standard. The specification discloses, in paragraph [0009], that anti-transketolase antibodies are naturally occurring upon Mtb infection. Additionally, the use of a standard to help quantify detection levels is well-known, routine, and conventional in the art of immunoassays (See Cox pg 6, “Standards or Antigen”). Therefore, claim 18 is not drawn to significantly more than the natural product of claim 8.
Together, one who understands what is well-known, routine, and conventional in the art of immunoassays would understand that the limitations of claims 9 and 12-18 are all commonly known in the art of immunoassays and are typically integrated together in a kit for performing immunoassays. Therefore, the limitations of these claims do not amount to significantly more than the natural product of claim 8, and claims 8, 9, and 12-18 are rejected under USC 101 as being directed to a judicial exception.
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.
Claims 8-10, 12, 14, and 16-17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2019/0055602 A1, Samavati et al., 2019 (hereinafter Samavati).
Instant claim 8 is drawn to an immunoassay kit comprising: as capture reagent, a peptide comprising the sequence of SEQ ID NO: 1, 12, 3 or 5, wherein the peptide forms a complex with an anti-transketolase antibody in the biological sample; and as detection reagent, a detectable anti-human IgG antibody, wherein the detectable anti- human IgG antibody binds to anti-transketolase antibody in the complex. Claims 9-18 further modify the kit of claim 8, with claim 9 disclosing the kit further comprises a solid support for the capture reagent, and claim 10 disclosing the capture reagent is immobilized on this solid support. Claim 12 discloses the kit of claim 8 with an additional detection means. Claim 14 discloses the amplification of the detectable antibody of claim 8 by a fluorometric reagent. Claim 16 specifies that the antibody of claim 8 is a monoclonal antibody, and claim 17 further specifies that this monoclonal antibody is a goat monoclonal antibody.
In Examples, Samavati teaches the use of a peptide comprising instant SEQ ID NO: 1, 3, and 5 in SEQ ID NO: 61, a peptide comprising and consisting of instant SEQ ID NO: 1 in SEQ ID NO: 62 and a peptide comprising and consisting of instant SEQ ID NO: 12 in SEQ ID NO: 60, to capture anti-TKT antibodies (See Table 4, Figure 9, and paragraphs [0264]-[0295]). Specifically, paragraph [0288] discloses these peptides immobilized on a microarray, which was interrogated with sera from tuberculosis (TB) patients that contained antibodies, and the binding of these antibodies was detected using red-fluorescent dye-labeled goat anti-human IgG antibodies (see also paragraph [0284]. This Example fully meets the limitations of claim 8, disclosing, as capture reagent, a peptide comprising the sequence of SEQ ID NO: 1, 12, 3 or 5, wherein the peptide forms a complex with an anti-transketolase antibody in the biological sample; and as detection reagent, a detectable anti-human IgG antibody, wherein the detectable anti-human IgG antibody binds to anti-transketolase antibody in the complex, and claims 16-17, as the detectable antibody is a goat monoclonal antibody. It also teaches the limitations of claims 9 and 10, which include the capture reagent immobilized on a solid support; in this case, the microarray plate. This Example includes a detection means for the detectable antibody as in instant claim 12 – in this case, a red fluorescent dye-label on the detecting antibody – which additionally teaches the limitation of claim 14, a fluorometric reagent.
Although these reagents are not necessarily in a ‘kit’, all meaningful limitations of instant claims 8-10, 12, 14, and 16-17 are disclosed in complex with each other in Samavati, and thus appear indistinguishable from the claimed kit. Therefore, Samavati anticipates the invention of instant claims 8-10, 12, 14, and 16-17.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 8-18 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0055602 A1, Samavati et al., 2019 (hereinafter Samavati) in view of Cox et al., Immunoassay Methods. 2012 May 1 [Updated 2019 Jul 8].
Instant claim 8 is drawn to an immunoassay kit comprising: as capture reagent, a peptide comprising the sequence of SEQ ID NO: 1, 12, 3 or 5, wherein the peptide forms a complex with an anti-transketolase antibody in the biological sample; and as detection reagent, a detectable anti-human IgG antibody, wherein the detectable anti- human IgG antibody binds to anti-transketolase antibody in the complex. Claims 9-18 further modify the kit of claim 8, with claim 9 disclosing the kit further comprises a solid support for the capture reagent, and claim 10 disclosing the capture reagent is immobilized on this solid support, and claim 11 further specifies this solid support is a microtiter plate. Claim 12 discloses the kit of claim 8 with an additional detection means, and claim 13 specifies this means is colorimetric. Claim 14 discloses the amplification of the detectable antibody of claim 8 by a fluorometric reagent, and claim 15 discloses that the detectable antibody of claim 8 is HRP-conjugated and another detection reagent is 3,3',5,5'-tetramethyl benzidine. Claim 16 specifies that the antibody of claim 8 is a monoclonal antibody, and claim 17 further specifies that this monoclonal antibody is a goat monoclonal antibody. Finally, claim 18 discloses that the kit of claim 8 contains an anti-transketolase antibody as a standard.
Samavati discloses a peptide comprising SEQ ID NO: 1, 3, and 5 in SEQ ID NO: 61, a peptide comprising and consisting of SEQ ID NO: 1 in SEQ ID NO: 62 and a peptide comprising and consisting of SEQ ID NO: 12 in SEQ ID NO: 60 (claim 8, capture reagent). Samavati discloses these peptides as markers that distinguish sarcoidosis from tuberculosis in humans, and the use of these markers in immunoassays and kits including materials and reagents necessary to conduct an immunoassay (e.g., ELISA) in paragraph [0103] (claim 8, immunoassay kit). Samavati discloses use of a probe, which can be an antibody, labeled with a detectable label (paragraph [0070]). Samavati discloses that the targets may be conjugated to a solid support suitable for a diagnostic assay in paragraph [0079], meeting the limitation of claim 9. Samavati teaches the immobilization of a capture reagent to a solid support in paragraph [0073], addressing the limitation of claim 10. Samavati discloses microtiter plates in paragraph [0083], addressing the limitation of claim 11. Paragraph [0073] of Samavati also teaches the use of horseradish peroxidase, also known as HRP, and fluorescent labels in accordance with known techniques, which meets the claim limitations of 12-15, as known techniques in the art are the use of HRP and 3,3',5,5'-tetramethyl benzidine (TMB), a colorimetric reaction, to evaluate antibody levels in an ELISA, and fluorometric amplification, a method of using fluorescence to evaluate antibody levels in an ELISA (see Cox et al.). Samavati teaches the use of a goat monoclonal antibody in paragraph [0269], meeting the limitations of claims 16 and 17, and teaches the use of a dataset derived from a standard sample in paragraph [0085], addressing the limitation of claim 18. Generally, Samavati teaches the concept of differentiating sarcoidosis from an Mtb infection by using an immunoassay kit to evaluate the level of anti-TKT antibodies in a sample (paragraphs [0050]-[0063]), and Samavati discloses anti-TKT antibodies as a distinct marker of tuberculosis infection (paragraph [0288] and table 4).
Finally, in Examples, Samavati teaches the use of SEQ ID NOs: 60, 62, and 61, which correspond to instant SEQ ID NOs: 1, 12, 3, or 5, to capture anti-TKT antibodies (See Table 4, Figure 9, and paragraphs [0264]-[0295]). These anti-TKT antibodies were detected with goat anti-human antibody, labeled with a red-fluorescent dye. This Example fully meets the limitations of claim 8, disclosing, as capture reagent, a peptide comprising the sequence of SEQ ID NO: 1, 12, 3 or 5, wherein the peptide forms a complex with an anti-transketolase antibody in the biological sample; and as detection reagent, a detectable anti-human IgG antibody, wherein the detectable anti-human IgG antibody binds to anti-transketolase antibody in the complex.
Samavati does not directly teach the coating of a microtiter plate with the immobilized peptide of SEQ ID NO: 1, 12, 3 or 5, or, specifically, the use of an anti-transketolase antibody as a standard. However, Cox et al., a review on the use of Immunoassays, discusses the most frequently used immunoassay formats, which include “antigen down” assays, stating “antigen-down immunoassays are used to bind antibodies found in a sample…” (page 8, Figure 3). Cox et al. thoroughly reviews all components considered when developing an ELISA, and so accounts for the limitations of claims 9-18: a solid support (page 3), immobilization on a microtiter plate (page 4, 8, and Figure 3), colorimetric detection means of HRP/TMB (page 6-7), or fluorometry (page 6-7), both mono- and polyclonal detectable antibodies (page 4, 29), and the use of an antibody standard to quantify an ELISA (page 18+). These are techniques commonly known in the art of immunoassays.
It would be obvious to one of ordinary skill in the art, before the effective filing date of the invention, to substitute the “antigen down” immunoassay technique of Cox with the kit containing the TKT antigen peptide of SEQ ID NO: 1, 12, 3, or 5, as disclosed in Samavati SEQ ID NO: 60-62, in order to capture anti-TKT antibodies, as disclosed in Samavati, and detect them with a monoclonal goat anti-human IgG antibody, as disclosed in Samavati. The results would be predictable to one of ordinary skill in the art, as the immobilization of an antigenic peptide is a known form of ELISA in the art, as shown by Cox et al.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that a claim would have been obvious if the substitution of one known element for another yields predictable results to one of ordinary skill in the art. It would be obvious to apply the known element of an antigen-down immunoassay for any other immunoassay to be used with a disclosed antigen to yield predictable results, such as detecting the presence of antibodies to the antigen. Thus, the combination of prior art references provides a prima facie case of obviousness, absent convincing evidence to the contrary.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia C Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645