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 11/30/2022. Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT/DE2021/000084, filed on 05/07/2021, which claims benefit of the foreign Application GERMANY 10 2020 003 794.1 filed on 06/25/2020.
Claim Status
Claims 1-26 are pending and examined.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claim 1 recites step “e) removing non-specifically bound molecules and particles” before step “f) binding the probes to the bioindicators.” While this implies a sequence order, the specification currently provides no support for this specific sequence. In contrast, the specification supports that step f) occurs before step e) (see pars.22, 61-62, 104, 106, 148-149). For example, Applicant discloses “after bringing the bioindicators into contact with the probes, non-specifically bound molecules and particles can be removed” in paragraph 22; “the sample/quantum medium mixture is applied to a substrate surface, for example a microtiter plate, the surface of which is likewise coated with a capture molecule, but which recognizes a different epitope on the bioindicator. Components not bound to the surface are removed” in paragraph 61. Therefore, the specification does not provide proper antecedent basis for the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-26 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 recites “particles” in step e/, claim 5 recites “particles” in line 5. There is insufficient antecedent basis for this limitation in the claims. First, it is unclear what these particles are and their roles in the claimed method. Second, it is unclear when particles are added into the claimed method because particles are not mentioned in steps a-d. Thus, it is unclear why particles are removed.
Claim 3 recites the limitation "these binding sites of the probes and/or capture molecules" in line 5. There is insufficient antecedent basis for this limitation in the claim because “binding sites of the probes and/or capture molecules” are not mentioned elsewhere in the previous claims 1-2. Only the binding sites of the bioindicators are recited in the previous claims 1-2.
Claim 6 recites “probes which bind to the bioindicators are selected, wherein the probes are also capable of emitting a specific signal.” The language of the claim creates confusion. It is unclear if “bind to the bioindicators” and “capable of emitting a specific signal” are the criteria for selecting the probes as supported in the specification paragraphs 23: “probes are selected which bind to the bioindicators, wherein the probes may, for example, also be capable of emitting a specific detection signal only after binding.” It is unclear if there are any other criteria for selecting the probes and what they are because the claim does not make clear what the subject matter is.
Claim 10 recites “the sample is fixed”, which is confusing because it is unclear if the intent is to claim that the sample is physically fixed on a substrate, as it appears to be no support for this specific sequence found in the specification. It is unclear if the sample is chemically fixed as supported in the specification paragraph 32.
Claim 16 depends on claim 15. While claim 15 recites “a hydrophilic surface”, claim 16 recites “the hydrophilic layer”. There is insufficient antecedent basis for “the hydrophilic layer” in the claim 16 because claim 15 recites “ surface” not “layer”.
Claim 18 recites “the gas phase”. There is insufficient antecedent basis for this limitation in the claim because “a gas phase” is not in claim 1.
Claim 19 recites “the coating”. There is insufficient antecedent basis for this limitation in the claim because “a coating” is not in claim 1.
Claim 23 recites a method of detecting a disease comprising the method of claim 1. Claim 1 recites steps of detecting bioindicators. It is unclear how to detect a disease based on the detection of bioindicators because claim 23 does not provide any further step after detecting bioindicators to link the bioindicators to a disease. Therefore, a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement.
Claim 24 recites a method of monitoring therapies with bioindicators and/or checking the effectiveness of active substances and/or therapeutic methods or determining if a person is to be included in a clinical study, comprising the method of claim 1. Claim 1 recites steps of detecting bioindicators. It is unclear how to monitor therapies, or check the effectiveness of active substances or therapeutic methods, or determine if a person is to be included in a clinical study after bioindicators are detected. Claim 24 does not provide any further step after detecting bioindicators to complete the claimed method. Therefore, a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement.
All dependent claims are also rejected based on their dependency of the defected parent claims.
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.
Claim(s) 23 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more.
Step 1 – Whether a claim is to a statutory category - YES
Claim 23 recites a method for detecting a disease comprising the method of claim 1. Therefore, the instantly claimed invention falls into one of the four statutory categories.
Step 2A Prong 1 – Whether the claim is directed to a judicial exception (i.e. Does the claim recite an abstract idea, law of nature, or natural phenomenon?) – YES
Claim 23 recites a method for detecting a disease comprising the method of claim 1, which recites a method of detecting bioindicators in the sample. The claim as a whole is regarded as a law of nature, namely, the naturally occurring correlation between the presence of bioindicators and a disease. Thus, claim 1 falls into a judicial exception.
Step 2A Prong 2 - Does the claim recite additional elements that integrate the judicial exception into a practical application? NO
The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception.
Claims 1 and 23 do not recite any additional element that integrate the exception into a practical application of the exception.
There are no subsequent steps recited after detecting a disease that would practically apply the method depending on the results of the measurements, e.g., treatment or other process steps that are performed after it is determined that the sample comprises bioindicators.
Step 2B: Whether the additional elements contribute an “inventive concept”
In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05.
The steps in claim 1 are insufficient to integrate the exception into a practical application because the purpose is merely to obtain data.
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, has been found to be insufficient to add “significantly more” (MPEP 2106.05(I)(A)).
The steps listed in claim 1 are well-understood, routine, and conventional. This position is supported by Koczula et al. (Lateral flow assays, Essays In Biochemistry, 2016, 111-120, IDS filed 03/03/2023) and Ganguly et al. (Development of an ultrasensitive hetero-sandwich ELISA assay based on bispecific monoclonal antibody for the detection of dengue NS1 protein, Journal Of Pharmacy Research, 7 (2013), 374-380).
Koczula teaches a method for detecting specific bioindicators in a sample (page 111, par.1) comprising specific biological components (i.e., capture molecules) immobilized on a membrane (i.e., substrate) (page 112, par.1, Fig.3). The role of specific biological components is to react with the analyte bound to the conjugated antibody which can emit a signal (i.e., probes) (pages 112-113, Principle of the lateral flow immunoassay and Fig.3).
Ganguly teaches a method for detecting specific bioindicators in a sample (Abstract) comprising: capture antibodies immobilized on a well surface to bind to dengue NS-1 proteins (i.e., bioindicators), HRPO conjugated antibodies (i.e., probes) to detect a complex of capture antibody and NS-1 protein (page 377, section 2.12.4).
Therefore, claim 23 is not drawn to eligible subject matter as it is directed to a law of nature without significantly more.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-19 and 21-26 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Zafiu (WO2018228625, Examiner discusses the teaching of Zafiu based on an English version of the application attached in PTO-892).
For claim 1, Zafiu teaches a method for the quantitative and/or qualitative determination of bioindicators (Zafiu page 3, lines 29-31), said method comprising the following steps: a) immobilizing capture molecules for the bioindicators on a substrate, b) bringing the bioindicators of a sample into contact with the capture molecules, c) immobilizing the bioindicators on the substrate by binding to capture molecules, d) bringing the bioindicators into contact with probes containing at least one detection molecule, and e) removing non-specifically bound molecules and particles, and f) binding the probes to the bioindicators, wherein the probes are capable of emitting a specific detection signal and steps b) and d) can take place simultaneously or d) before b) (Zafiu page 3 lines 33-40 teaches steps a to f, wherein extracellular vesicles in Zafiu are bioindicators).
Zafiu teaches wherein probes have affine molecules or molecule parts that bind to at least one specific binding site of the bioindicators (Zafiu page 4 lines 7-8); and capture molecules have affine molecules or molecule parts that bind to at least one specific binding site of the bioindicators (Zafiu page 2 lines 55-58: teaches that capture molecules binds to extracellular vesicles, page 5 lines 35-40: teaches that capture molecules are affine to a characteristic of the extracellular vesicle to be detected); and these affine molecules or molecule parts of the probes and capture molecules do not overlap one another (Zafiu page 2 lines 45-57: teaches that the extracellular vesicles in the sample are immobilized on the substrate by binding to the capture molecules and are detected by the probes; page 3 lines 5-10: teaches extracellular vesicles which contain at least one binding site for a capture molecule and at least one binding site for a probe; these teaching supports these affine molecules of the probes and capture molecules do not overlap one another because the complexes of the capture molecules - extracellular vesicles - the probes are formed).
For claims 2-3, Zafiu teaches the method of claim 1. Zafiu teaches that at least two or more different capture molecules and probes are used simultaneously (Zafiu page 6 lines 29-32), which the capture molecules and probes can have different affine molecules or parts of molecules (Zafiu page 4 lines 13-16, lines 52-53). The use of a plurality of different probes enables the identification of extracellular vesicles which differ in one or more characteristics. This allows selective quantification and characterization of the extracellular vesicles. Zafiu page 4 lines 18-21. This teaching of Zafiu encompasses that the affine molecules or molecule parts of the probes and/or capture molecules bind to at least two specific binding sites of the bioindicators and/or bind to at least two different binding sites of at least two different bioindicators (e.g., probes can detect different types of extracellular vesicles).
For claim 4, Zafiu teaches the method of claim 3, wherein by bringing the bioindicators into contact with the capture molecules, said bioindicators are immobilized on the substrate by binding to the capture molecules. (Zafiu page 2 lines 55-58)
For claim 5, Zafiu teaches the method of claim 1, wherein after bringing the bioindicators into contact with the probes, non-specifically bound molecules and particles are removed by washing. Zafiu page 3 lines 1-5.
For claim 6, Zafiu teaches the method of claim 1, wherein probes which bind to the bioindicators are selected, wherein the probes are also capable of emitting a specific signal. Zafiu page 3 lines 1-5, page 7 lines5-15)
For claim 7, Zafiu teaches the method of claim 1, wherein the detection molecules of the probes comprise fluorochromes and/or fluorescent proteins (Zafiu page 6 lines 34-39).
For claim 8, Zafiu teaches the method of claim 1, wherein the bringing of the bioindicators into contact with the capture molecules and the probes takes place simultaneously. Zafiu page 3 lines 5-10.
For claim 9, Zafiu teaches the method of claim 1, wherein the bringing of the bioindicators into contact with the probes takes place prior to bringing the bioindicators into contact with the capture molecules. Zafiu page 3 lines 5-10.
For claim 10, Zafiu teaches the method of claim 1, wherein the sample is fixed prior to binding the probes to the bioindicators. Zafiu page 3 lines 45-55 teaches that a detergent is used after the chemical fixation in order to make the membrane of the extracellular vesicle permeable and, for example, during the binding of the probes to the extracellular vesicles, probes can penetrate into the interior of the extracellular vesicles.
For claim 11, Zafiu teaches the method of claim 1, wherein quantum dots are used instead of probes, which quantum dots are coated with capture molecules having affine molecules or molecule parts which bind to at least one specific binding site of the bioindicators. (Zafiu page 6 lines 36-41 teaches that the probes are labeled with fluorescent dyes or, alternatively, quantum dots. The probe in Zafiu also comprises an affine molecule that recognizes and binds to a binding site of the extracellular vesicle, which is a capture molecule (Zafiu page 4 lines 5-11). The teaching of Zafiu above encompasses quantum dots are coated with capture molecules having affine molecules or molecule parts which bind to at least one specific binding site of the bioindicators.)
For claim 12, Zafiu teaches the method of claim 1, wherein the sample is treated with detergents. Zafiu page 3 lines 53-55.
For claim 13, Zafiu teaches the method of claim 1, wherein a spatially resolved determination of the probe signal takes place. Zafiu page 4 lines 23-25.
For claim 14, Zafiu teaches the method of claim 1, wherein the substrate comprises plastic, silicon or silicon dioxide, and/-or glass. Zafiu page 4 lines 42-45.
For claim 15, Zafiu teaches the method of claim 1, wherein the substrate has a hydrophilic surface prior to immobilizing capture molecules on the substrate. Zafiu page 4 lines 45-50.
For claim 16, Zafiu teaches the method of claim 15, wherein the hydrophilic layer is selected from the group comprising or consisting of PEG, poly-lysine and dextran, or derivatives thereof. Zafiu page 4 lines 58-60.
For claim 17, Zafiu teaches the method of claim 1, wherein functionalization with amino groups is effected by bringing the substrate into contact with APTES (3-aminopropyl-trietoxy silane) or ethanolamine. Zafiu page 5 lines 1-5.
For claim 18, Zafiu teaches the method of claim 1, wherein bringing the substrate into contact with APTES (3-aminopropyl-trietoxy silane) takes place in the gas phase. Zafiu page 5 lines 24-25.
For claim 19, Zafiu teaches the method of claim 1, wherein the capture molecules are covalently bonded to the substrate or to the coating. Zafiu page 5 lines 35-36.
For claim 21, Zafiu teaches the method of claim 1, wherein the probes are marked with fluorescent dyes. Zafiu page 6 lines 36-41.
For claim 22, Zafiu teaches the method of claim 1, wherein detection takes place by spatially resolving fluorescence microscopy. Zafiu page 6 lines 55-57.
For claim 23, Zafiu teaches a method for detecting a disease, comprising the method of claim 1. Zafiu page 7 lines 59-60.
For claim 24, Zafiu teaches a method for monitoring therapies with bioindicators and/or checking the effectiveness of active substances and/or therapeutic methods or determining if a person is to be included in a clinical study, comprising the method of claim1. Zafiu page 8 lines 5-10.
For claim 25, Zafiu teaches a kit for carrying out the method according to claim 1, wherein the kit comprises: substrate, capture molecules; and probe molecules. Zafiu page 2 lines 38-45, page 7 lines 32-45.
For claim 26, Zafiu teaches a kit for carrying out the method according to claim 1, wherein the kit comprises: substrate, - capture molecules; and Qdots, wherein the Qdots are coated with capture molecules having affine molecules or molecule parts which bind to at least one specific binding site of the bioindicators. Zafiu page 2 lines 38-45, page 4 lines 5-11, page 6 lines 36-41. See discussion about quantum dots coated with capture molecules having affine molecules or molecule parts which bind to at least one specific binding site of the bioindicators in claim 11.
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.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zafiu (WO2018228625) in view of Sedlak (US20220155304).
For claim 20, Zafiu teaches the method of claim 1, wherein the binding sites of the bioindicators are multi-specific epitopes (Zafiu page 3 lines 29-31: teaches that extracellular vesicles contain at least one binding site for a capture molecule and at least one binding site for a probe). Note: in light of the specification paragraphs 52 and 125, the “binding sites of the bioindicators are multi-specific epitopes” is interpreted as the bioindicators have multiple epitopes.
Zafiu teaches that at least two or more different capture molecules and probes are used simultaneously (Zafiu page 6 lines 29-32), which the capture molecules and probes can have different affine molecules or parts of molecules (Zafiu page 4 lines 13-16, lines 52-53). The use of a plurality of different probes enables the identification of extracellular vesicles which differ in one or more characteristics. This allows selective quantification and characterization of the extracellular vesicles. Zafiu page 4 lines 18-21. This teaching of Zafiu encompasses that the affine molecules or molecule parts of the probes and/or capture molecules bind to at least two specific binding sites of the bioindicators and/or bind to at least two different binding sites of at least two different bioindicators (e.g., probes can detect different types of extracellular vesicles).
Zafiu does not teach that the affine molecules or molecule parts of the capture molecules and/or probes are multi-specific antibodies or parts thereof.
Sedlak teaches a method for the quantitative and/or qualitative determination of bioindicators (see Abstract and par.7: teaching technologies for use in detecting an entity of interest comprising at least two or more targets, e.g., extracellular vesicles, wherein the at least two or more targets may be the same or distinct). The method comprises the following steps:
a) immobilizing capture molecules for the bioindicators on a substrate (see par.33 and par.459: “an exemplary capture agent for an extracellular vesicle-associated membrane-bound polypeptide may be or comprise a solid substrate (e.g., a magnetic bead) and a binding moiety (e.g., an antibody agent) directed to an extracellular vesicle-associated membrane-bound polypeptide.”),
b) bringing the bioindicators of a sample into contact with the capture molecules (see par.20: “immobilizing an entity of interest (e.g., a biological entity) to be assayed on a solid substrate”, par.33: teaches that the solid substrate comprises capture molecules which binds to an entity of interest),
c) immobilizing the bioindicators on the substrate by binding to capture molecules (see par.20, 33, and 459),
d) bringing the bioindicators into contact with probes containing at least one detection molecule (see par.21 and 459).
Sedlak teaches that the antibodies used in capture beads and probes refer to agents that specifically bind to a particular antigen, wherein the antibodies are bi- or multi-specific antibodies (see par.94).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Zafiu, by substituting capture molecules and probes of Zafiu for the bi- or multi-specific antibodies to detect extracellular vesicles as taught by Sedlak. It is obvious to use the known technique (multi-specific antibodies) taught by Sedlak to replace a plurality of capture molecules and probes taught by Zafiu because they are functionally equivalent in terms of binding to at least two specific binding sites of the bioindicators so that the method can identify extracellular vesicles which differ in one or more characteristics. The monospecific affine molecules in Zafiu or multi-specific antibodies in Sedlak can be used interchangeably as capture molecules and probes with a reasonable expectation of success.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Zafiu and Sedlak because they are directed to a sandwich immunoassay to detect an analyte of interest on extracellular vesicles in the sample.
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 1-19 and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,175,288 (‘288) in view of Zafiu (WO2018228625). Although the claims at issue are not identical, they are not patentably distinct from each other because:
For claims 1 and 23, claims 1-3 of ‘288 teach a method for the qualitative and / or quantitative determination of disease indicators comprising step a-d and f of the instant claim 1. Claims 1-3 of ‘288 also teach wherein probes have affine molecules or molecule parts that bind to at least one specific binding site of the bioindicators; and capture molecules have affine molecules or molecule parts that bind to at least one specific binding site of the bioindicators; and these affine molecules or molecule parts of the probes and capture molecules do not overlap one another.
The ‘288 does not teach step e of the instant claim 1.
Zafiu teaches methods recited in claims 1 and 23 as discussed in claim 1 above, which comprises step e; and steps b/ and d/ can take place simultaneously or d/ before b/ (Zafiu page 3 lines 33-40).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘288, by removing non-specifically bound molecules and particles as taught by Zafiu, for the benefit of improving the sensitivity of the test by reducing background signal from non-specifically bound probes (Zafiu page 6 lines 45-55).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by ‘288, by doing steps b/ and d/ simultaneously or doing d/ before b/ as taught by Zafiu because Zafiu teaches that these are alternative ways to bring the indicators into contact with the probes and the capture molecules which results in a predictable outcome, e.g., forming a complex of capture molecules, bioindicators, and probes.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘288 and Zafiu because they are directed to a sandwich immunoassay to detect an analyte of interest in the sample.
For claims 4, 6-7, 13, 21, claims 1-3 of ‘288 encompass the limitations of these claims.
For claims 2-3, 5, 8-11, 14-19, 22,and 24-26, ‘288 and Zafiu teach the method in claim 1. ‘288 does not teach the limitations in these claims.
Zafiu teaches the limitations in these claims. See discussion of Zafiu above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the method of ‘288 and Zafiu for the benefit of detecting and quantifying a bioindicator on any desired samples by simple steps (Zafiu page 3 lines 24-25). One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘288 and Zafiu because ‘288 is generic for a sandwich immunoassay to detect an analyte of interest in the sample and Zafiu provides a specific sandwich immunoassay to detect an analyte of interest in the sample.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,175,288 (‘288) in view of Zafiu (WO2018228625) and Sedlak (US20220155304). Although the claims at issue are not identical, they are not patentably distinct from each other because:
For claim 20, ‘288 and Zafiu teach the method of claim 1. ‘288 does not teach that the affine molecules or molecule parts of the capture molecules and/or probes are multi-specific antibodies or parts thereof.
Zafiu teaches that the binding sites of the bioindicators are multi-specific epitopes (Zafiu page 3 lines 29-31: teaches that extracellular vesicles contain at least one binding site for a capture molecule and at least one binding site for a probe). Note: in light of the specification paragraphs 52 and 125, the “binding sites of the bioindicators are multi-specific epitopes” is interpreted as the bioindicators have multiple epitopes.
Zafiu teaches that at least two or more different capture molecules and probes are used simultaneously (Zafiu page 6 lines 29-32), which the capture molecules and probes can have different affine molecules or parts of molecules (Zafiu page 4 lines 13-16, lines 52-53). The use of a plurality of different probes enables the identification of extracellular vesicles which differ in one or more characteristics. This allows selective quantification and characterization of the extracellular vesicles. Zafiu page 4 lines 18-21. This teaching of Zafiu encompasses that the affine molecules or molecule parts of the probes and/or capture molecules bind to at least two specific binding sites of the bioindicators and/or bind to at least two different binding sites of at least two different bioindicators (e.g., probes can detect different types of extracellular vesicles).
Zafiu does not teach that the affine molecules or molecule parts of the capture molecules and/or probes are multi-specific antibodies or parts thereof.
Sedlak teaches a method for the quantitative and/or qualitative determination of bioindicators comprising steps a-d of the instant claim 1 (see Abstract and par.7, 20-21, 33, and 459), wherein the bioindicators are extracellular vesicles. See discussion of Sedlak in claim 20 above. Sedlak teaches that the antibodies used in capture beads and probes refer to agents that specifically bind to a particular antigen, e.g., bi- or multi-specific antibodies (see par.94).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of ‘288 and Zafiu, by substituting capture molecules and probes of ‘288 and Zafiu for the bi- or multi-specific antibodies to detect extracellular vesicles as taught by Sedlak. It is obvious to use the known technique (multi-specific antibodies) taught by Sedlak to replace a plurality of capture molecules and probes taught by ‘288 and Zafiu because they are functionally equivalent in terms of binding to at least two specific binding sites of the bioindicators so that the method can identify extracellular vesicles which differ in one or more characteristics. The monospecific affine molecules in ‘288 and Zafiu or multi-specific antibodies in Sedlak can be used interchangeably as capture molecules and probes with a reasonable expectation of success.
One having an ordinary skill in the art would have had a reasonable expectation of success in combining ‘288 and Zafiu and Sedlak because they are directed to a sandwich immunoassay to detect an analyte of interest on extracellular vesicles in the sample.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHAU N.B. TRAN whose telephone number is (571)272-3663. The examiner can normally be reached Mon-Fri 8:30-6:30 CT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached on 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 February 24, 2026