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 was filed on 06/02/2023, which claims benefit of U.S. Provisional Patent Application 63/348,755 filed on 06/03/2022.
Claim status
Claims 1-20 are pending and examined herein.
Claim Objections
Claims 1, 11, and 20 are objected to because of the following informalities:
Claim 1 recites “A method for measuring an antibody to in a dried sample…”. The word “to” in the claim is redundant.
Claim 11 recites “…wherein the first antigen: SARS-CoV-2 antibody: second antigen complex…”. It appears that the antigen-antibody complex is commonly presented by the hyphen between antigen and antibody rather than the colon.
Claim 20 lines 4 appears lacking a word --for-- after “a component or station”.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities: page 8 line 10, no quotation mark after quantitative assay.
Appropriate correction is required.
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.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
Claims 16 and 20: recite “a component or station for obtaining a dried sample from a subject, a component or station for extracting the antibody from the sample, and a component or station for detecting the antibody extracted from the sample.”
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
Claim limitation “a component or station for obtaining a dried sample from a subject” is limited by the description in page 3 of the specification, which comprises a DBS card.
Claim limitation “a component or station for extracting the antibody from the sample” is limited by the description in page 14 of the specification, which comprises a tube containing a diluent.
Claim limitation “a component or station for detecting the antibody extracted from the sample” is limited by the description in page 9 of the specification, which comprises analytical techniques, e.g., a Roche Elecsys Anti-SARS-CoV-2 S electrochemiluminescence immunoassay.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 3 and 6 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 3 recites wherein the step of detecting the antibody is semi-quantitative or quantitative. The definition of semi-quantitative or quantitative is not recited in the claim. The claim does not disclose any method step to quantitate or semi-quantitate the antibody in the sample. Thus, one having an ordinary skill in the art is not clear how the antibody is detected. While the specification discloses the definition of "a semi-quantitative assay" or "quantitative assay” in page 8, the definition is not put in the claim. Therefore, the claim is indefinite for failing to particularly point out and distinctly claim the subject matter.
Claim 6 depends on claim 1 and recites the limitation "the assay". There is insufficient antecedent basis for this limitation in the claim because no assay has been mentioned in claim 1.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-2, 4-6, 15-17, and 19-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Knoop et al. (Detection of anti-SARS-CoV-2 antibodies in dried blood spots utilizing manual or automated spot extraction and electrochemiluminescence immunoassay (ECLIA), Anal Sci Adv.2021; 2: 440–446, IDS 04/09/2025).
For claim 1, Knoop teaches a method for measuring an antibody in a dried sample from a subject (see Title, Abstract) comprising: (a) obtaining the dried sample from the subject (see Abstract: teaching that test results obtained from minimal-invasively collected dried blood spot (DBS) specimens, see page 441 section 2.3: teaching that up to 4 spots of approximately 20 µL of capillary blood were collected by a finger-prick onto the cellulose-based DBS cards); (b) extracting the antibody from the dried sample (see Abstract: teaching that DBS samples were prepared for analysis either manually or by a card extraction robot, see page 441 section 2.3); and (c) detecting the antibody extracted from the dried sample (see page 442 section 2.5).
For claim 2, Knoop teaches the method of claim 1, wherein the antibody is a SARS-CoV-2 antibody (see Title and Abstract).
For claims 4 and 19, Knoop teaches the method of claim 1 and claim 16, wherein the dried sample is a dried blood spot (DBS) (see at least in Title and Abstract).
For claim 5, Knoop teaches the method of claim 1, wherein the dried sample is dried plasma or dried serum (see Abstract: teaching that the dried sample is dried blood spot which comprises dried plasma or dried serum because plasma or serum is a part of the blood). One having an ordinary skill in the art would have had a reasonable expectation of success in detecting the antibody in dried plasma or dried serum because the analysis system Cobas e411 analyzer for immunoassay testing can detect antibody in all employed matrices, e.g., serum, plasma and DBS (see page 442 section 2.5).
For claim 6, Knoop teaches the method of claim 1, wherein an assay is an electrochemiluminescence immunoassay (see at least in Title and page 442 section 2.5).
For claim 15, Knoop teaches the method of claim 2, further comprising obtaining measurements from an individual over a period of time to follow the titer of SARS-CoV-2 antibody in the individual. See Abstract: teaching that test results obtained from individuals tested twice within 10 months post-infection indicated a consistent presence of antibodies.
For claim 16, Knoop teaches a system for measuring an antibody in a dried sample comprising: (a) a component or station for obtaining a dried sample from a subject (see page 441 section 2.1: teaching that DBS collection was conducted using Hemaxis DB 10 collection devices); (b) a component or station for extracting the antibody from the sample (see page 441 section 2.3: teaching that for extraction purposes, the DBS was punched and quartered into 1.5 mL microcentrifuge tubes before addition of 100 µL of the EDTA solution and 10 min of ultra-sonication); and (c) a component or station for detecting the antibody extracted from the sample (see page 442 section 2.5: teaching a Cobas e411 analyzer for immunoassay testing and an ECLIA Elecsys Anti-SARS-CoV-2 were for the detection of anti-SARS-CoV-2 antibodies). See more supports in page 441 sections 2.2 and 2.4 and Figure 1 for a component or station for obtaining a dried sample from a subject (e.g., cellulose-based DBS cards) or extracting the antibody from the sample (e.g., a Dried Blood Spot Autosampler).
For claim 17, Knoop teaches the method of claim 16, wherein the antibody is a SARS-CoV-2 antibody (see Title and Abstract).
For claim 20, Knoop teaches a computer-program product tangibly embodied in a non-transitory machine-readable storage medium, including instructions configured to run at least in part at least one of: (a) a component or station for obtaining a dried sample from a subject; (b) a component or station for extracting the antibody from the sample; and (c) a component or station detecting the antibody extracted from the sample. See page 441-442, section 2.4: teaching that the automated extraction workflow was programmed to obtain a dried sample (e.g., the left MultiPurpose Samplers (MPS) inserts a card from a card rack into the DBS), extract the antibody (e.g., a volume of 85 µL is transported as a segmented volume through the capillaries). See page 444 section 3.1.5: teaching that the sample extracts are completely transferred into the sampling tubes for the ECLIA cobas e411 analyzer.
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) 3 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Knoop et al., as applied to claims 1 and 16 above, in view of Roche-2020 (Roche launches new quantitative antibody test to measure SARS-CoV-2 antibodies, to support the evaluation of vaccines, September 17, 2020).
For claims 3 and 18, Knoop teaches the method of claim 1 and claim 16. While Knoop teaches that the test for detecting anti-SARS-CoV-2 antibodies is electrochemiluminescence immunoassay (ECLIA) (see at least in Title), Knoop does not clearly teach wherein the step of detecting the antibody is semi-quantitative or quantitative.
Roche-2020 teaches a new ECLIA test that can quantitatively measure the level of antibodies against SARS-CoV-2 (see pages 1-2: teaching that the test targets antibodies which are directed against the particular region of the viral spike protein). The new ECLIA test is important to vaccine design and efficacy evaluations because the majority of current candidate vaccines aim to induce an antibody response against the spike protein (see page 2 par.1-4). Moreover, the test is also used for understanding how to contain the spread of the virus, as well as how to safely ease lockdown restrictions (see page 2 par.4).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the detecting ECLIA method of Knoop by the ECLIA method of Roche-2020 to quantify the Anti-SARS-CoV-2 antibodies in the dried blood sample. A person of ordinary skill in the art would have been motivated to use the ECLIA kit of Roche-2020 because the kit of Roche-2020 can help to more effectively determine the percentage of a population who already have antibodies against SARS-COV-2 and support the evaluation of vaccines (see Roche-2020 page 1).
A skilled artisan would have had a reasonable expectation of success in combining Knoop and Roche-2020 because they are directed to the ECLIA method of detecting antibody to SARS-CoV-2 in the sample.
Claim(s) 7, 9-11 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Knoop or, in the alternative, under 35 U.S.C. 103 as obvious over Knoop et al., as applied to claims 2 and 16 above, in view of Roche (Elecsys Anti-SARS-CoV-2, 2021).
For claim 7, Knoop teaches the method of claim 2, wherein the antibody is measured using a sandwich assay employing a first antigen that recognizes the SARS-CoV-2 antibody and is labeled with a detectable moiety and a second antigen that recognizes the SARS-CoV-2 antibody (see page 442 section 2.5: teaching that the detection principle is based on an electrically induced chemiluminescent emission after formation of a sandwich complex where present anti-SARS-CoV-2 antibodies are targeted by two nucleocapsid antigens, one labeled with a tris(2,2′-bipyridyl)ruthenium(II)-complex).
While Knoop teaches that the method of detecting SARS-CoV-2 antibody is Cobas e411 analyzer from Roche, Knoop does not teach that the second antigen is labeled with a binding agent.
In addition, Roche teaches an Elecsys Anti-SARS-CoV-2 Cobas e411 immunoassay intended for qualitative detection of antibodies to SARS-CoV-2 in human serum and plasma (see page 1 Intended use par.1, and page 2 Test principle). Roche further teaches that the second antigen is labeled with a binding agent (see page 2 Test principle: teaching that the first SARS-CoV-2-specific recombinant antigen is labeled with a ruthenium and the second SARS-CoV-2-specific recombinant antigen is labeled with biotin. The first and second antigens form a sandwich complex with the antibody in the sample).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of detecting SARS-CoV-2 taught by Knoop also comprises the second antigen labeled with a binding agent. It is because Knoop uses the Cobas e411 kit from Roche and Roche supports that the second antigen is labeled with a binding agent, e.g., biotin.
For claim 9, Knoop and Roche teach the method of claim 7, wherein the detectable moiety on the first antigen is an electrochemical moiety and optionally, is ruthenium (see Knoop page 442 section 2.5).
For claims 10-11, Knoop and Roche teach the method of claim 7. Knoop does not teach wherein the binding agent is streptavidin as in claim 10. Knoop does not teach wherein the first antigen- SARS-CoV-2 antibody- second antigen complex is bound to a biotin-labeled electrode such that application of a voltage results in a chemiluminescent emission as in claim 11.
However, Knoop teaches that the method of detecting SARS-CoV-2 antibody is Cobas e411 analyzer from Roche.
Roche teaches the test principle of the electrochemiluminescence immunoassay “ECLIA” comprising forming a sandwich complex between biotinylated SARS-CoV-2-specific recombinant antigen and SARS-CoV-2-specific recombinant antigen labeled with a ruthenium and antibodies against SARS-CoV-2 in the sample (see page 2 Test principle). Next, the sandwich complex binds to the streptavidin-coated solid phase which captured onto the electrode (see page 2 Test principle). Then, a voltage is applied to the electrode and induces chemiluminescent emission which is measured by a photomultiplier (see page 2 Test principle). This teaching encompasses that the first antigen- SARS-CoV-2 antibody- second antigen complex is bound to a labeled electrode such that application of a voltage results in a chemiluminescent emission.
Although Roche does not teach that the binding agent in the second antigen is streptavidin and the electrode is coated with biotin, Roche teaches the complex becomes bound to the solid phase via interaction of biotin and streptavidin, wherein the biotin is on the second antigen and streptavidin is on the electrode as discussed above. The linking method taught by Roche and the linking method in the instant application share the similar concept of capturing the antigen-antibody complex on the electrode via interaction of biotin and streptavidin. One of ordinary skill in the art would have been aware that the linking method taught by Roche is an alternative solution to capture the antigen-antibody complex on the electrode, which uses the common pair binding partners (e.g., biotin-streptavidin). Thus, a skilled artisan would have had a reasonable expectation of success in swapping the binding agents in the pair binding partners on the second antigen and the electrode, and the swapping would yield predictable results.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Knoop et al. in view of Roche, as applied to claim 7 above, and further in view of Roche-2020 (Roche launches new quantitative antibody test to measure SARS-CoV-2 antibodies, to support the evaluation of vaccines, September 17, 2020) and Public Health England (Evaluation of Roche Elecsys AntiSARS-CoV-2 S serology assay for the detection of anti-SARS-CoV-2 S antibodies, May 2021).
For claim 8, Knoop and Roche teach the method of claim 7. Roche teaches that the first SARS-CoV-2-specific recombinant antigen labeled with a ruthenium and the second biotinylated SARS-CoV-2-specific recombinant antigen form a sandwich complex with the antibody in the sample. Roche teaches that the first and second antigens recognize antibodies to nucleocapsid protein (see page 2 Summary: teaching that the Elecsys Anti-SARS-CoV-2 assay uses a recombinant protein representing the nucleocapsid (N) antigen for the determination of antibodies against SARS-CoV-2). Knoop and Roche do not teach wherein the first and second antigens recognize antibodies to SARS-CoV-2 spike protein.
Roche-2020 teaches an Elecsys Anti-SARS-CoV-2 S serology test that can measure the level of antibodies against SARS-CoV-2 spike protein (see pages 1-2: teaching that the test targets antibodies which are directed against the particular region of the viral spike protein). The test is important to vaccine design and efficacy evaluations because the majority of current candidate vaccines aim to induce an antibody response against the spike protein (see page 2 par.1-4). Moreover, the test is also used for understanding how to contain the spread of the virus, as well as how to safely ease lockdown restrictions (see page 2 par.4).
Public Health England also teaches the Elecsys Anti-SARS-CoV-2 S for the detection of anti-SARS-CoV-2 spike protein antibodies in serum samples (see page 4). Public Health England further teaches a sandwich complex of the first SARS-CoV-2-specific recombinant antigen labeled with a ruthenium, the second biotinylated SARS-CoV-2-specific recombinant antigen, and the antibody in the sample is formed and is bound to the surface of the electrode (see page 6 Test Principle).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the detecting ECLIA method of Knoop in view of Roche by the ECLIA method of Roche-2020 to quantify the Anti-SARS-CoV-2 spike protein antibodies in the dried blood sample. A person of ordinary skill in the art would have been motivated to use the ECLIA kit of Roche-2020 because the kit of Roche-2020 can help to more effectively determine the percentage of a population who already have antibodies against SARS-COV-2 and support the evaluation of vaccines (see Roche-2020 page 1). Accordingly, the modified method of Knoop can comprise that the first and the second antigens recognize antibodies to SARS-CoV-2 spike protein as taught by Public Health England.
A skilled artisan would have had a reasonable expectation of success in combining Knoop, Roche, Roche-2020, and Public Health England because they are directed to the ECLIA method of detecting antibody to SARS-CoV-2 in the sample. Moreover, the ECLIA method of Roche shares the same test principle with the ECLIA method of Roche-2020 and Public Health England. Therefore, the modification would result in the predictable outcome.
Claim(s) 12-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Knoop et al. in view of Roche, as applied to claim 11 above, and further in view of Roche-2020 (Roche launches new quantitative antibody test to measure SARS-CoV-2 antibodies, to support the evaluation of vaccines, September 17, 2020), Public Health England (Evaluation of Roche Elecsys AntiSARS-CoV-2 S serology assay for the detection of anti-SARS-CoV-2 S antibodies, May 2021), and Simundic (Measures of diagnostic accuracy: basic definitions, 2008).
For claims 12-14, Knoop, Roche, Roche-2020 and Public Health England teach the method of claim 11. Knoop does not teach the limitations in claims 12-14.
Public Health England teaches that the limit of detection (LOD) for the SARS-CoV-2 antibody is 0.4 U/ml, the upper limit of quantitation (ULOQ) for the SARS-CoV-2 antibody is 250 U/ml, and the cutoff for positivity for the SARS-CoV-2 antibody is set to 0.8 U/ml.
Knoop teaches that the amount of antibodies in DBS compared to that in serum or plasma at the same taken volume is lower because of the potential analyte loss and dilution during the extraction process (see page 442 section 3.1.1). The cutoff-level for DBS samples is adjusted to account for a reduced overall assay sensitivity (see page 442 section 3.1.1).
While Knoop in view of Roche, Roche-2020 and Public Health England do not specifically teach the same values of LOD, ULOQ, and cutoff for the SARS-CoV-2 antibody detection in dried blood spot sample, they teach the values of LOD, ULOQ and cutoff for the SARS-CoV-2 antibody detection in serum and plasma sample and suggest that the values of LOD, ULOQ and cutoff for the SARS-CoV-2 antibody detection in DBS should be adjusted because the amount of antibodies in DBS is lower than that in serum and plasma at the same volume.
Simundic teaches that a perfect diagnostic procedure has the potential to completely discriminate subjects with and without disease. Values of a perfect test which are above the cut-off are always indicating the disease, while the values below the cut-off are always excluding the disease (see page 205 par.1). This discriminative potential can be quantified by the measures of diagnostic accuracy such as sensitivity and specificity, etc. (see Abstract and Introduction). However, measures of a test performance are not fixed indicators of a test quality and performance. Measures of diagnostic accuracy are very sensitive to the characteristics of the population in which the test accuracy is evaluated. See page 204.
Therefore, one having ordinary skill in the art would have been aware that the values of LOD, ULOQ, and cutoff in the assay are varied and are defined by the user based on the characteristics of the population in which the test accuracy is evaluated to provide the best possible evidence for health care providers, clinicians and laboratory professionals; to the best for the patient care (see Simundic page 211).
One having ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed values of LOD, ULOQ, and cutoff for the SARS-CoV-2 antibody detection in DBS through routine optimization procedures known in the art, e.g., the teachings of Knoop, Public Health England and Simundic.
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.
Claims 1-2, and 4-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 14-16 of copending Application No. 17/845,502 (‘502). Although the claims at issue are not identical, they are not patentably distinct from each other.
For claims 1-2, claim 1 of ‘502 anticipates the limitations of the claims.
For claims 4-5, claims 1 and 5 of ‘502 anticipate the limitations of the claims.
For claim 6, claims 1, 14, 16 of ‘502 encompass the limitation of the claim.
For claim 7, claim 1 step (c) of ‘502 anticipates the limitation of the claim.
For claim 9, claim 14 of ‘502 anticipates the limitation of the claim.
For claim 10, claim 15 of ‘502 anticipates the limitation of the claim.
For claim 11, claim 16 of ‘502 anticipates the limitation of the claim.
Claims 3 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 14-16 of copending Application No. 17/845,502 (‘502) in view of Roche-2020 (Roche launches new quantitative antibody test to measure SARS-CoV-2 antibodies, to support the evaluation of vaccines, September 17, 2020) and Public Health England (Evaluation of Roche Elecsys AntiSARS-CoV-2 S serology assay for the detection of anti-SARS-CoV-2 S antibodies, May 2021).
For claims 3 and 8, claim 1 of ‘502 teaches the method of claim 1. The ‘502 does not clearly teach wherein the step of detecting the antibody is semi-quantitative or quantitative as in claim 3, and wherein the first and second antigens recognize antibodies to SARS-CoV-2 spike protein as in claim 8.
Roche-2020 teaches a new electrochemiluminescence immunoassay (ECLIA) test that can quantitatively measure the level of antibodies against SARS-CoV-2 (see pages 1-2: teaching that the test targets antibodies which are directed against the particular region of the viral spike protein). The new ECLIA test is important to vaccine design and efficacy evaluations because the majority of current candidate vaccines aim to induce an antibody response against the spike protein (see page 2 par.1-4). Moreover, the test is also used for understanding how to contain the spread of the virus, as well as how to safely ease lockdown restrictions (see page 2 par.4).
Public Health England also teaches the Elecsys Anti-SARS-CoV-2 S for the detection of anti-SARS-CoV-2 spike protein antibodies in serum samples (see page 4). Public Health England further teaches a sandwich complex of the first SARS-CoV-2-specific recombinant antigen labeled with a ruthenium, the second biotinylated SARS-CoV-2-specific recombinant antigen, and the antibody in the sample is formed and is bound to the surface of the electrode (see page 6 Test Principle).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the detecting method of ‘502 by the method of Roche-2020 and Public Health England to quantify the Anti-SARS-CoV-2 spike protein antibodies in the dried blood sample. A person of ordinary skill in the art would have been motivated to use the ECLIA kit of Roche-2020 because the kit of Roche-2020 can help to more effectively determine the percentage of a population who already have antibodies against SARS-COV-2 and support the evaluation of vaccines (see Roche-2020 page 1). Accordingly, the modified method of ‘502 can comprise that the first and the second antigens recognize antibodies to SARS-CoV-2 spike protein as taught by Public Health England.
A skilled artisan would have had a reasonable expectation of success in combining ‘502, Roche-2020, and Public Health England because they are directed to the ECLIA method of detecting antibody to SARS-CoV-2 in the sample. Moreover, the ECLIA method of ‘502 shares the same test principle with the ECLIA method of Roche-2020 and Public Health England, which measures the antibody using a sandwich assay employing a first antigen labeled with a detectable moiety and a second antigen labeled with a binding agent. Therefore, the modification would result in the predictable outcome.
Claims 12-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 14-16 of copending Application No. 17/845,502 (‘502) in view of Roche-2020 (Roche launches new quantitative antibody test to measure SARS-CoV-2 antibodies, to support the evaluation of vaccines, September 17, 2020), Public Health England (Evaluation of Roche Elecsys AntiSARS-CoV-2 S serology assay for the detection of anti-SARS-CoV-2 S antibodies, May 2021), and Simundic (Measures of diagnostic accuracy: basic definitions, 2008).
For claims 12-14, claim 1 of ‘502 teaches the method of claim 11. The ‘502 does not teach the limitations in claims 12-14.
The ‘502 in view of Roche-2020, and Public Health England teach the quantitative method of detecting antibody to SARS-CoV-2 spike protein in the sample as discussed in claim 8 above.
Claim 1 of ‘502 teaches the cutoff index for determining if a test sample is positive or negative.
Public Health England teaches that the limit of detection (LOD) for the SARS-CoV-2 antibody is 0.4 U/ml, the upper limit of quantitation (ULOQ) for the SARS-CoV-2 antibody is 250 U/ml, and the cutoff for positivity for the SARS-CoV-2 antibody is set to 0.8 U/ml.
Simundic teaches that a perfect diagnostic procedure has the potential to completely discriminate subjects with and without disease. Values of a perfect test which are above the cut-off are always indicating the disease, while the values below the cut-off are always excluding the disease (see page 205 par.1). This discriminative potential can be quantified by the measures of diagnostic accuracy such as sensitivity and specificity, etc. (see Abstract and Introduction). However, measures of a test performance are not fixed indicators of a test quality and performance. Measures of diagnostic accuracy are very sensitive to the characteristics of the population in which the test accuracy is evaluated. See page 204.
The ‘502 and Public Health England do not specifically teach the same values of LOD, ULOQ, and cutoff for the SARS-CoV-2 antibody detection in sample, they teach the need of setting the cutoff value to determine if the antibody in the sample has a detectable amount. Simundic teaches that the measures of diagnostic accuracy such as cutoff value, sensitivity and specificity are varied based on the characteristics of the population.
Therefore, one having ordinary skill in the art would have been aware that the values of LOD, ULOQ, and cutoff in the assay are varied and are defined by the user based on the characteristics of the population in which the test accuracy is evaluated to provide the best possible evidence for health care providers, clinicians and laboratory professionals; to the best for the patient care (see Simundic page 211).
One having ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed values of LOD, ULOQ, and cutoff for the SARS-CoV-2 antibody detection in DBS through routine optimization procedures known in the art, e.g., the teachings of ‘502, Roche-2020, Public Health England and Simundic.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims are rejected.
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/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 January 15, 2026