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 .
Response to Amendment
The Amendment filed October 16, 2025 has been entered. Claims 1-31 remain pending in the application.
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 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 14, 16 and 18-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carney et al. (US 2004/0181172 A1) (“Carney”).
Regarding claim 14, Carney discloses A method for analyte capture using an ocular insert, the method comprising (Abstract and entire document)b:
inserting the ocular insert into a portion of an eye of a patient ([0088], “The method comprises the steps of: providing a contact lens capable of binding the analyte of interest; wearing the contact lens on an eye of an individual for a period of time so that an amount of the analyte of interest is absorbed by the contact lens;”),
wherein the ocular insert is comprised of one or more surface-bound capture agents, wherein the one or more surface-bound capture agents bind to and concentrate at least one target analyte from tear fluid ([0090], “In accordance with the present invention, a contact lens of the invention can be used to collect one or more analytes of interest, since a plurality of receptors, each for a specific analyte of interest can be incorporated into the contact lens of the invention.”);
wherein the concentration of the at least one target analyte within the ocular insert increases over time as the ocular insert remains within the eye of a patient due to a cumulative binding of analyte molecules and a retention of captured analytes within a microenvironment of the ocular insert ([0092], “The method comprises the steps of: providing a contact lens capable of binding the analyte of interest; wearing the contact lens on an eye of an individual for a period of time, preferably 30 minutes or longer, more preferably 2 hour or longer, so that an amount of the analyte of interest is absorbed by the contact lens;”);
removing the ocular insert from the patient after the concentration of at least one of the target analytes has increased ([0092], “removing the contact lens containing the amount of the analyte of interest from the eye;” after absorption the lens is removed.); and
performing an assay to analyze the composition of the ocular insert ([0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
Regarding claim 16, Carney discloses The method of claim 14, wherein the ocular insert is a contact lens containing the one more surface-bound capture agents ([0012], “This invention is based largely on the discovery that a contact lens, preferably a daily disposable contact lens, can be used to collect one or more analytes of interest in tear fluid, and in turn, determine the physiological state or health of a subject.”).
Regarding claim 18, Carney discloses The method of claim 14, further comprising: removing the ocular insert from the patient ([0092], “removing the contact lens containing the amount of the analyte of interest from the eye;”);
washing the ocular insert to remove any non-specifically bound tear constituents ([0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.” Washing is well known within the art of bioassays, see further [0100] and [0104] describing washing for the assay.); and
performing a bioassay to analyze remaining analytes specifically bound to the one or more capture agents ([0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
Regarding claim 19, Carney discloses The method of claim 14, further comprising: extracting one or more analytes specifically-bound to the one or more capture agents from the ocular insert via an eluting buffer; and analyzing the one or more analytes ([0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
Regarding claim 20, Carney discloses The method of claim 19, wherein extracted analytes are analyzed via liquid chromatography, mass spectrometry, gel electrophoresis, or a combination thereof ([0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
Regarding claim 21, Carney discloses The method of claim 14, wherein a colorimetric, fluorescence, or chemo-, electro-, or photo-luminescence bioassay is performed to analyze constituents collected by the ocular insert ([0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-2, 4, 6-8, 12-13 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Flitsch et al. (US 2017/0026790 A1) (“Flitsch”) in view of Carney et al. (US 2004/0181172 A1) (“Carney”).
Regarding claim 1, Flitsch discloses An lacrimal punctal insert for capturing and concentrating one or more target analytes in vivo in bodily fluid comprising (Abstract and entire document, see at least [0177] describing the device as a punctal plug for analyzing analytes in biofluid):
one or more surface-bound capture agents ([0045] and [0079] – [0089], “A more generic set of techniques relate to fluorescence probes that have constituents that bind to analyte molecules and in so alter a fluorescence signature.”),
wherein each of the one or more surface-bound capture agents specifically binds and concentrates at least one target analyte of the one or more target analytes from tear fluid ([0045] and [0079] – [0089], “A more generic set of techniques relate to fluorescence probes that have constituents that bind to analyte molecules and in so alter a fluorescence signature…. The binding of an analyte to the FRET probes may yield a fluorescence signal that is sensitive to glucose concentrations.”);
Flitsch fails to disclose wherein the concentration of the at least one target analyte within the lacrimal punctal insert increases over time as the lacrimal punctal insert remains within the eye of a patient due to a cumulative binding of analyte molecules and a retention of captured analytes within a microenvironment of the lacrimal punctal insert.
However, in the same field of endeavor, Carney teaches wherein the concentration of the at least one target analyte within the lacrimal punctal insert increases over time as the lacrimal punctal insert remains within the eye of a patient due to a cumulative binding of analyte molecules and a retention of captured analytes within a microenvironment of the lacrimal punctal insert ([0012], “The contact lens may be in its native form or may be modified to selectively enhance adsorption of one or more analytes of interest. By wearing a contact lens capable of binding one or more analytes of interest, over a period of time, for example, 15 minutes or longer, preferably one hour or longer, more preferably 2 hours or longer, even more preferably 4 hours or longer, most preferably 8 hours or longer, the one or more analytes of interest can be enriched over the period of wearing time, since the tear fluid in a normal human eye is continuously replenished. By using a contact lens capable of binding an analyte of interest in a tear fluid, one can determine the concentration of an analyte of interest accumulated over a period of time and therefore the effects of biological concentration variability on the determined concentration of the one or more analytes of interest can be minimized.” While Carney is directed to contact lenses, the teachings apply to the modification with Flitsch, such that the lacrimal punctal insert is modified with the increased concentration and binding taught by Carney).
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 lacrimal punctal insert as taught by Flitsch to include wherein the concentration of the at least one target analyte within the lacrimal punctal insert increases over time as the lacrimal punctal insert remains within the eye of a patient due to a cumulative binding of analyte molecules and a retention of captured analytes within a microenvironment of the lacrimal punctal insert as taught by Carney to improve accuracy ([0012], “Therefore, the accuracy of assays for the analytes in a body fluid can be greatly enhanced.”).
Regarding claim 2, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch further discloses wherein the at least one of the one or more surface-bound capture agents is comprised of at least one of an antibody that binds one or more specific proteins, a protein that binds one or more specific proteins, ions, oligonucleotides and/or polynucleotides, an oligonucleotide or polynucleotide that binds one or more specific oligonucleotides or polynucleotides, or a molecularly imprinted polymer ([0078], “Biomedical devices may be configured to read and analyze proteins, bacteria, viruses, changes in temperature, changes in pH, metabolites, electrolytes, and other such analytes used in diagnostic medicine and analytical chemistry.” And [0079 - 0083], “For example, in Förster Resonance Energy Transfer (FRET), probes are configured with a combination of two fluorophores that may be chemically attached to interacting proteins.”).
Regarding claim 4, Flitsch as modified discloses The lacrimal punctal insert of claim 1, further comprising: one or more hollow channels, wherein the one or more hollow channels contain the one or more surface-bound capture agents, enabling the tear fluid to access capture agents on interior surfaces of the lacrimal punctal insert (see at least [0177] describing the device as a punctal plug for analyzing analytes in biofluid, wherein a punctal plug discloses the limitation of the one or more hollow channels).
Regarding claim 6, Flitsch as modified discloses The lacrimal punctal insert of claim 4, Flitsch further discloses wherein the one or more hollow channels extend continuously through the lacrimal punctal insert, enabling the tear fluid to drain naturally through the lacrimal punctal insert into a lacrimal canaliculi (see at least [0177] describing the device as a punctal plug for analyzing analytes in biofluid, wherein a punctal plug discloses the limitation of the one or more hollow channels).
Regarding claim 7, Flitsch as modified discloses The lacrimal punctal insert of claim 4, Flitsch further discloses wherein the one or more hollow channels do not fully permeate the lacrimal punctal insert, so the lacrimal punctal insert may act as a punctal plug to block the drainage of the tear fluid through a lacrimal canaliculi (see at least [0177] describing the device as a punctal plug for analyzing analytes in biofluid, wherein a punctal plug discloses the limitation of the one or more hollow channels).
Regarding claim 8, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch further discloses wherein the at least one target analyte is at least one of an organic compound, a biomarker, pharmacological agent, a synthetic organic compound, an environmental pathogen, a metal ion, a virus, a bacteria, a fungus, an enzyme, a metabolite, a lipid, a phospholipid, a glycolipid, an extracellular vesicle, an oligonucleotide, a polynucleotide, microRNA, a protein, and a peptide ([0078], “Biomedical devices may be configured to read and analyze proteins, bacteria, viruses, changes in temperature, changes in pH, metabolites, electrolytes, and other such analytes used in diagnostic medicine and analytical chemistry.” And [0079 - 0083], “For example, in Förster Resonance Energy Transfer (FRET), probes are configured with a combination of two fluorophores that may be chemically attached to interacting proteins.”).
Regarding claim 12, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch further discloses wherein the one or more surface-bound capture agents are a small molecule, a drug, a metabolite, an anion, a cation, a charged polymer, an oligosaccharide, a polysaccharide, a lipid, a glycolipid, a phospholipid, a metallic surface, a metal oxide or a combination thereof ([0078], “Biomedical devices may be configured to read and analyze proteins, bacteria, viruses, changes in temperature, changes in pH, metabolites, electrolytes, and other such analytes used in diagnostic medicine and analytical chemistry.” And [0079 - 0083], “For example, in Förster Resonance Energy Transfer (FRET), probes are configured with a combination of two fluorophores that may be chemically attached to interacting proteins.”).
Regarding claim 13, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch further discloses wherein the one or more surface-bound capture agents are comprised of viral capture nanoparticles or microparticles ([0078], “Biomedical devices may be configured to read and analyze proteins, bacteria, viruses, changes in temperature, changes in pH, metabolites, electrolytes, and other such analytes used in diagnostic medicine and analytical chemistry.” And [0079 - 0083], “For example, in Förster Resonance Energy Transfer (FRET), probes are configured with a combination of two fluorophores that may be chemically attached to interacting proteins.”).
Regarding claim 30, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch fails to explicitly disclose wherein the concentration within the lacrimal punctal insert of at least one of the one or more target analytes is increased by at least a factor of 1.2 as compared to the concentration of the analyte in the surrounding bodily fluid (Flitsch teaches in [0012], “The contact lens may be in its native form or may be modified to selectively enhance adsorption of one or more analytes of interest. By wearing a contact lens capable of binding one or more analytes of interest, over a period of time, for example, 15 minutes or longer, preferably one hour or longer, more preferably 2 hours or longer, even more preferably 4 hours or longer, most preferably 8 hours or longer, the one or more analytes of interest can be enriched over the period of wearing time, since the tear fluid in a normal human eye is continuously replenished. By using a contact lens capable of binding an analyte of interest in a tear fluid, one can determine the concentration of an analyte of interest accumulated over a period of time and therefore the effects of biological concentration variability on the determined concentration of the one or more analytes of interest can be minimized.” Such that the concentration is increased by a desired factor).
It would have been obvious to one of ordinary skill in the art, through routine optimization, to determine the optimal factor for increasing, including 1.2. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Since applicant has not disclosed that this limitation solves any stated problem or is for any particular purpose and it appears that the device would perform equally well with either designs. Absent a teaching as to criticality that the factor in this particular arrangement is deemed to have been known by those skilled in the art since the instant specification and evidence of record fail to attribute any significance (novel or unexpected results) to a particular arrangement.
Regarding claim 31, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch further discloses wherein the concentration within the lacrimal punctal insert of at least one of the one or more target analytes is increased to an amount that it becomes detectable as compared to the concentration of the analyte in the surrounding bodily fluid ([0012], “The contact lens may be in its native form or may be modified to selectively enhance adsorption of one or more analytes of interest. By wearing a contact lens capable of binding one or more analytes of interest, over a period of time, for example, 15 minutes or longer, preferably one hour or longer, more preferably 2 hours or longer, even more preferably 4 hours or longer, most preferably 8 hours or longer, the one or more analytes of interest can be enriched over the period of wearing time, since the tear fluid in a normal human eye is continuously replenished. By using a contact lens capable of binding an analyte of interest in a tear fluid, one can determine the concentration of an analyte of interest accumulated over a period of time and therefore the effects of biological concentration variability on the determined concentration of the one or more analytes of interest can be minimized.” Such that the concentration is increased by a desired factor to be detectable).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Flitsch et al. (US 2017/0026790 A1) (“Flitsch”) in view of Carney et al. (US 2004/0181172 A1) (“Carney”) in further view of Ashton (US 2005/0163844 A1) (“Ashton”).
Regarding claim 3, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch fails to disclose wherein the one or more surface-bound capture agents are comprised of at least one of a metal-binding ligand, an aptamer, a DNAzyme or, molecularly imprinted polymers.
However, in the same field of endeavor, Ashton teaches wherein the one or more surface-bound capture agents are comprised of at least one of a metal-binding ligand, an aptamer, a DNAzyme or, molecularly imprinted polymers (FIG. 1 and para. [0004, 0005, 0022, 0023, 0149, 0150], para. [0023], “The class includes hammerhead ribozymes, minimized hammerheads ("minizymes"), '10-23' deoxyribozymes ("DNAzymes"), and the like.”).
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 lacrimal punctal insert as taught by Flitsch to include wherein the one or more surface-bound capture agents are comprised of at least one of a metal-binding ligand, an aptamer, a DNAzyme or, molecularly imprinted polymers as taught by Ashton in order to recognize certain target molecules (Para. [0023], “comprises nucleic acids that are capable of recognizing and catalyzing the cleavage of target RNA molecules,”).
Claims 5 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Flitsch et al. (US 2017/0026790 A1) (“Flitsch”) in view of Carney et al. (US 2004/0181172 A1) (“Carney”) in further view of Xiao (US 2017/0135637 A1) (“Xiao”).
Regarding claim 5, Flitsch as modified discloses The lacrimal punctal insert of claim 1, Flitsch fails to disclose further comprising: a porous material wherein pores contain the one or more surface-bound capture agents, enabling the tear fluid to access the one or more capture agents on interior surfaces of the lacrimal punctal insert.
However, in the same field of endeavor, Xiao teaches further comprising: a porous material wherein pores contain the one or more surface-bound capture agents, enabling the tear fluid to access the one or more capture agents on interior surfaces of the lacrimal punctal insert (FIG. 1 and para. [0015] – [0019], “In some embodiments, FRET system 122 may be encapsulated into a membrane containing physiologically compatible porous nanostructures such that FRET system 122 may be substantially retained on or within the physiologically compatible porous nanostructures.”).
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 lacrimal punctal insert as taught by Flitsch to include further comprising: a porous material wherein pores contain the one or more surface-bound capture agents, enabling the tear fluid to access the one or more capture agents on interior surfaces of the lacrimal punctal insert as taught by Xiao to substantially retain the capture agents/analyte monitoring system ([0042], “In some embodiments, FRET system 122 may be encapsulated into a membrane including physiologically compatible porous nanostructures such that FRET system 122 may be substantially retained on or within the physiologically compatible porous nanostructures.”).
Regarding claim 9, Flitsch as modified discloses The lacrimal punctal insert of claim 4, Flitsch fails to disclose wherein the one or more surface-bound capture agents are bound to one or more separate scaffold materials embedded within the one or more hollow channels and pores of the lacrimal punctal insert.
However, in the same field of endeavor, Xiao teaches wherein the one or more surface-bound capture agents are bound to one or more separate scaffold materials embedded within the one or more hollow channels and pores of the lacrimal punctal insert (FIG. 1 and para. [0015] – [0022], fret system 122 may be encapsulated withing physiologically compatible porous nanostructures such as fluorescent mesoporous silica nanoparticles within borehole 110.).
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 lacrimal punctal insert as taught by Flitsch to include wherein the one or more surface-bound capture agents are bound to one or more separate scaffold materials embedded within the one or more hollow channels and pores of the lacrimal punctal insert as taught by Xiao to substantially retain the capture agents/analyte monitoring system ([0042], “In some embodiments, FRET system 122 may be encapsulated into a membrane including physiologically compatible porous nanostructures such that FRET system 122 may be substantially retained on or within the physiologically compatible porous nanostructures.”).
Regarding claim 10, Flitsch as modified discloses The lacrimal punctal insert of claim 9, Flitsch fails to disclose wherein at least one or more of the separate scaffold materials are comprised of microparticles or labeled microparticles.
However, in the same field of endeavor, Xiao teaches wherein at least one or more of the separate scaffold materials are comprised of microparticles or labeled microparticles (FIG. 1 and para. [0015] – [0022], fret system 122 may be encapsulated withing physiologically compatible porous nanostructures such as fluorescent mesoporous silica nanoparticles within borehole 110.).
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 lacrimal punctal insert as taught by Flitsch to include wherein at least one or more of the separate scaffold materials are comprised of microparticles or labeled microparticles as taught by Xiao to substantially retain the capture agents/analyte monitoring system ([0042], “In some embodiments, FRET system 122 may be encapsulated into a membrane including physiologically compatible porous nanostructures such that FRET system 122 may be substantially retained on or within the physiologically compatible porous nanostructures.”).
Regarding claim 11, Flitsch as modified discloses The lacrimal punctal insert of claim 10, Flitsch fails to disclose wherein the labeled microparticles are contained within an open channels by a removable membrane, which upon removing, enables the labeled microparticles to be released for in-vitro analysis.
However, in the same field of endeavor, Carney teaches wherein the labeled microparticles are contained within an open channels by a removable membrane, which upon removing, enables the labeled microparticles to be released for in-vitro analysis ([0092], “removing the contact lens containing the amount of the analyte of interest from the eye;… “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
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 lacrimal punctal insert as taught by Flitsch to include wherein the labeled microparticles are contained within an open channels by a removable membrane, which upon removing, enables the labeled microparticles to be released for in-vitro analysis as taught by Carney to improve accuracy ([0012], “Therefore, the accuracy of assays for the analytes in a body fluid can be greatly enhanced.”).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Xiao (US 2017/0135637 A1) (“Xiao”).
Regarding claim 15, Carney discloses The method of claim 14, Carney fails to disclose wherein the ocular insert is a lacrimal punctal insert for insertion into a lacrimal punctum and contains the one or more surface-bound capture agents.
However, in the same field of endeavor, Xiao teaches wherein the ocular insert is a lacrimal punctal insert for insertion into a lacrimal punctum and contains the one or more surface-bound capture agents (FIG. 1 and para. [0015], “Plug 102 may be adapted for placement in a lacrimal punctum of an eyelid of a subject” and para. [0018], “For example, FRET system 122 may be adapted for a fluorescence-based chromatographic assay, and a glucose level in the tears of subject 116 may be determined based on the fluorescence-based chromatographic assay.”).
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 as taught by Carney to include wherein the ocular insert is a lacrimal punctal insert for insertion into a lacrimal punctum and contains the one or more surface-bound capture agents as taught by Xiao to result in sustainable measurement ([0014], “In some embodiments, the plug may be placed or implanted in an eyelid (for example, a lacrimal punctum), resulting in sustainable non-invasive measurement of glucose levels in tears while not affecting oxygen supply to ocular tissues.”).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Roy et al. (US 2014/0309554 A1) (“Roy”).
Regarding claim 17, Carney discloses The method of claim 14, Carney fails to disclose wherein the ocular insert fits into a conjunctival sac of the patient and contains the one or more surface-bound capture agents.
However, in the same field of endeavor, Roy teaches wherein the ocular insert fits into a conjunctival sac of the patient (FIG. 1 and 2 and para. [0092] – [0094], sampling device includes a tube 209 to be placed in the conjunctival sac 107.)
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 as taught by Carney to include wherein the ocular insert fits into a conjunctival sac of the patient as taught by Roy in order to obtain more lacrimal fluid as the majority of tears are stored in the conjunctive sac (FIG. 1 and para. [0011], “Most of the tear fluid is stored in the conjunctival sac 107”).
Claims 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Microba life sciences limited (WO 2019/237158 A1) (“Microba”).
Regarding claim 22, Carney discloses The method of claim 14, Carney fails to disclose wherein one or more of the surface-bound capture agents are designed to capture one or more oligonucleotides or polynucleotides, wherein PCR, RT-PCR, LAMP, RT-LAMP or gene sequencing are performed to analyze constituents collected by the ocular insert (FIG. 1 and para. [0015] – [0019], [0022] and [0050], “An analyte can be in the solid, liquid, gaseous or vapor phase. The term analyte may include polynucleotide analytes such as those polynucleotides defined below. These include m-RNA, r-RNA, t-RNA, DNA, DNA-RNA duplexes, etc. The term analyte also includes receptors that are polynucleotide binding agents,”),
However, in the same field of endeavor, Microba teaches wherein PCR, RT-PCR, LAMP, RT-LAMP or gene sequencing are performed to analyze constituents collected by the ocular insert (FIG. 1 and para. [0022, 0121, 0122, 0125, 0128, 0155], samples are collected from the eye and processed, including amplifying the nucleic acids using PCR, RT-PCR, LAMP or whole gene sequencing.).
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 as taught by Carney to include wherein PCR, RT-PCR, LAMP, RT-LAMP or gene sequencing are performed to analyze constituents collected by the ocular insert as taught by Microba in order to generate a microbiome sequence dataset (Para. [0019], “generating a microbiome sequence dataset”).
Regarding claim 23, Carney discloses The method of claim 14, Carney fails to disclose wherein one or more of the surface-bound capture agents are comprised of an oligonucleotide or polynucleotide, wherein one or more oligonucleotide or polynucleotide capture agents are released from the ocular insert and analyzed by PCR, RT-PCR, LAMP, RT-LAMP or gene sequencing.
However, in the same field of endeavor, Microba teaches wherein one or more oligonucleotide or polynucleotide capture agents are released from the ocular insert and analyzed by PCR, RT-PCR, LAMP, RT- LAMP or gene sequencing (FIG. 1 and para. [0022, 0121, 0122, 0125, 0128, 0155], samples are collected from the eye and processed, including purifying the sample by using binding moiety-bound particles configured to bind nucleic acids and configured to release nucleic acids in the presence of an elution environment, and processing further includes amplifying the nucleic acids using PCR, RT-PCR, LAMP, or whole gene sequencing).
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 as taught by Carney to include wherein the one or more oligonucleotide or polynucleotide capture agents are released from the ocular insert and analyzed by PCR, RT-PCR, LAMP, RT- LAMP or gene sequencing as taught by Microba in order to generate a microbiome sequence dataset (Para. [0019], “generating a microbiome sequence dataset”).
Claims 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Polsky et al. (US 2018/0338713 A1) (“Polsky”).
Regarding claim 24, Carney discloses The method of claim 14, Carney further discloses further comprising: removing the ocular insert from the patient ([0092], “removing the contact lens containing the amount of the analyte of interest from the eye;” after absorption the lens is removed.);
Carney fails to disclose inserting the ocular insert into a microfluidic device; and
injecting, using the microfluidic device, one or more washing buffers, reagents, eluting buffers or a combination thereof, into the ocular insert, prior to performing a bioassay.
However, in the same field of endeavor, Polsky teaches inserting the ocular insert into a microfluidic device (FIG. 22 and para. [0136, 0137, 0152, 0164], a microfluid module may be inserted between a disposable needle and the electrode sensors.); and
injecting, using the microfluidic device, one or more washing buffers, reagents, eluting buffers or a combination thereof, into the ocular insert, prior to performing a bioassay (FIG. 21A-22 and para. [0136, 0152-0154, 0204], samples bound to magnetic beads and washed with the samples attached to beads before eluting the beads to remove the DNA; after binding, washing and extracting the analytes, the samples are flowed into the sensor well with a microelectrode array for immune assays).
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 as taught by Carney to include inserting the ocular insert into a microfluidic device; and injecting, using the microfluidic device, one or more washing buffers, reagents, eluting buffers or a combination thereof, into the ocular insert, prior to performing a bioassay as taught by Polsky in order to deactivate the enzyme before testing (Para. [0154], “After the DNA is digested, valve three (V3 in FIG. 21A or one or more valves 2115 in FIG. 21B) is actuated, and an EDTA (ethylenediaminetetraacetic acid) wash from chamber 5 deactivates the restriction enzyme. The EDTA wash is then used to push the contents of chamber 6 onto the microelectrode sensor array for analysis (e.g., a detector, such as a detector module, including any herein, such as an electrode array sensor 2120 in FIG. 21B).”).
Regarding claim 25, Carney discloses The method of claim 14, Carney fails to disclose wherein the one or more surface-bound capture agents are removed from the ocular insert prior to performing a bioassay.
However, in the same field of endeavor, Polsky teaches wherein the one or more surface-bound capture agents are removed from the ocular insert prior to performing a bioassay (FIG. 21A-22 and para. [0136, 0152-0154, 0204], samples bound to magnetic beads and washed with the samples attached to beads before eluting the beads to remove the DNA; after binding, washing and extracting the analytes, the samples are flowed into the sensor well with a microelectrode array for immune assays).
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 as taught by Carney to include wherein the one or more surface-bound capture agents are removed from the ocular insert prior to performing a bioassay as taught by Polsky in order to deactivate the enzyme before testing (Para. [0154], “After the DNA is digested, valve three (V3 in FIG. 21A or one or more valves 2115 in FIG. 21B) is actuated, and an EDTA (ethylenediaminetetraacetic acid) wash from chamber 5 deactivates the restriction enzyme. The EDTA wash is then used to push the contents of chamber 6 onto the microelectrode sensor array for analysis (e.g., a detector, such as a detector module, including any herein, such as an electrode array sensor 2120 in FIG. 21B).”).
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Microba life sciences limited (WO 2019/237158 A1) (“Microba”) in further view of Polsky et al. (US 2018/0338713 A1) (“Polsky”).
Regarding claim 26, Carney as modified discloses The method of claim 23, Carney fails to disclose wherein the one or more surface-bound capture agents are bound to the surface of the ocular insert and/or a porous scaffold material within the ocular insert via a cleavable bond, wherein the cleavable bond is cleaved to release the one or more surface-bound capture agents to perform a bioassay.
However, in the same field of endeavor, Polsky teaches wherein the one or more surface-bound capture agents are bound to the surface of the ocular insert and/or a porous scaffold material within the ocular insert via a cleavable bond, wherein the cleavable bond is cleaved to release the one or more surface-bound capture agents to perform a bioassay (FIG. 21A-22; paragraphs [0136, 0152-0154, DNA samples bound to magnetic beads are cleaved in chamber 6 to separate them from the beads and then moved on electrodes for an immunoassay).
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 as taught by Carney as modified to include via a cleavable bond, wherein the cleavable bond is cleaved to release the surface-bound capture agents to perform a bioassay as taught by Polsky in order to in order to deactivate the enzyme before testing (Para. [0154], “After the DNA is digested, valve three (V3 in FIG. 21A or one or more valves 2115 in FIG. 21B) is actuated, and an EDTA (ethylenediaminetetraacetic acid) wash from chamber 5 deactivates the restriction enzyme. The EDTA wash is then used to push the contents of chamber 6 onto the microelectrode sensor array for analysis (e.g., a detector, such as a detector module, including any herein, such as an electrode array sensor 2120 in FIG. 21B).”).
Claims 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Microba life sciences limited (WO 2019/237158 A1) (hereinafter – Microba) in further view of Xiao (US 2017/0135637 A1) (“Xiao”).
Regarding claim 27, Carney as modified discloses The method of claim 23, Carney fails to disclose wherein the ocular insert comprises microparticles as a capture-agent-immobilizing scaffold, prior to performing a bioassay.
However, in the same field of endeavor, Xiao teaches wherein the ocular insert comprises microparticles as a capture-agent-immobilizing scaffold, prior to performing a bioassay (FIG. 1 and para. [0015] – [0022], fret system 122 may be encapsulated withing physiologically compatible porous nanostructures such as fluorescent mesoporous silica nanoparticles within borehole 110.).
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 as taught by Carney as modified to include via a cleavable bond, wherein the cleavable bond is cleaved to release the surface-bound capture agents to perform a bioassay as taught by Xiao to substantially retain the capture agents/analyte monitoring system ([0042], “In some embodiments, FRET system 122 may be encapsulated into a membrane including physiologically compatible porous nanostructures such that FRET system 122 may be substantially retained on or within the physiologically compatible porous nanostructures.”).
Regarding claim 28, Carney as modified discloses The method of claim 27, Carney as modified further discloses further comprising: and performing flow cytometry, a fluorescence, colorimetric, chemo-, electro-, or photo- luminescence assay, or a combination thereof, on the released microparticles (Carney [0092], “determining the presence or the amount of the analyte of interest.” And [0093 – 0094], “Any known suitable assays can be used in the present invention. Exemplary assays include, without limitation, radioimmunoassay (RIA), enzyme immunoassay (EIA), immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), assays based on Trinder reaction, electrochemical assay, and the like.”).
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Carney et al. (US 2004/0181172 A1) (“Carney”) in view of Luloh et al. (US 2018/0074074 A1) (“Luloh”).
Regarding claim 29, Carney discloses The method of claim 14, Carney fails to disclose wherein at least two distinct analytes are specifically captured by the ocular insert, wherein the ocular insert is first removed from the patient, and the concentrations of the two or more distinct analytes are measured with respect to one another in order to yield a multiplex bioassay.
However, in the same field of endeavor, Luloh teaches wherein at least two distinct analytes are specifically captured by the ocular insert, wherein the ocular insert is first removed from the patient, and the concentrations of the two or more distinct analytes are measured with respect to one another in order to yield a multiplex bioassay ([0064], “In certain embodiments, the assay platform is configured for multiplex detection of more than one analyte. Such assays employ two or more capture molecules, each of which specifically binds an analyte, and two or more detection methods so that the binding of each analyte can be determined. In preferred assays of this type, the target analytes include an angiogenic ocular analyte and an inflammatory ocular analyte. The dual detection can be performed in a single container where all the reagents for both assays are mixed together, or in two separate containers or vessels.”).
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 as taught by Carney to include wherein at least two distinct analytes are specifically captured by the ocular insert, wherein the ocular insert is first removed from the patient, and the concentrations of the two or more distinct analytes are measured with respect to one another in order to yield a multiplex bioassay as taught by Luloh to detect more than one analyte ([0064], “In certain embodiments, the assay platform is configured for multiplex detection of more than one analyte. Such assays employ two or more capture molecules, each of which specifically binds an analyte, and two or more detection methods so that the binding of each analyte can be determined. In preferred assays of this type, the target analytes include an angiogenic ocular analyte and an inflammatory ocular analyte. The dual detection can be performed in a single container where all the reagents for both assays are mixed together, or in two separate containers or vessels.”).
Response to Arguments
Applicant's arguments filed October 16, 2025 have been fully considered but they are not persuasive. With respect to the arguments regarding the section 102 rejections, the arguments are not persuasive. Applicant argues that Carney fails to disclose cumulative binding. It is interpreted that cumulative binding is increasing binding of analyte to the capture agents. Carney directly discloses increasing binding of analyte to capture agents with time. See [0092], cited in the rejection above, discussing leaving the device in the eye to accumulate binding. Thus, the arguments are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the structural limitations for cumulative binding that are argued on page 11 of the Remarks) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Simply arguing that there is specific structure required to perform cumulative binding, is not suffice, there is none of that claimed, and further claim 14 is a method claim. Regarding the arguments directed toward claim 18, the arguments are not persuasive. [0100], [0104] discuss washing. Further, washing in regards to immunoassays is well known within the art. Thus, the arguments are not persuasive. With respect to the arguments regarding claim 19, applicant arguments rely on the fact that there is no cumulative binding. Thus, the arguments are not persuasive. The arguments regarding claims 20-21 again argue the different binding mechanisms and concentration of binding, which are not claimed features. Thus, the arguments are not persuasive.
With respect to the arguments regarding the section 103 rejections, the arguments are not persuasive. Applicant again argues that Flitch and Carney fails to disclose cumulative binding of analyte to capture agent, increasing over time. The arguments are not persuasive for the reasons discussed above. With respect to the arguments regarding claims 3, 5, 9-11. The combination of Flitch, Carney, and further Xiao for claims 5, 9-11 is used. Thus, the cumulative binding of Carney is in the combination. Thus, the arguments are not persuasive. With respect to the rejections regarding claims 15, 17 and 22-29, the arguments are moot.
Regarding the arguments of claims 22-23, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Carney discloses the capture agents and the capture agents being polynucleotides as claimed. Thus, the arguments are not persuasive. Microba further teaches the PCR techniques.
Regarding the arguments of claims 24-25, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Carney discloses the capture agents in the device and Polsky teaches insertion of a device for analysis. Thus, the arguments are not persuasive.
With respect to the arguments regarding claims 26, the arguments are not persuasive. Polsky discloses cleaving for a bioassay. Thus, the arguments are not persuasive.
With respect to the arguments regarding claims 27-28, the arguments are not persuasive. Xiao teaches the nanostructures/scaffolds/microparticles as claimed, thus the arguments are not persuasive.
With respect to the arguments regarding claim 29, the assay as taught by Flitch/Carney is an ocular insert, in the eye, in vivo, thus the arguments are not persuasive.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH A TOMBERS whose telephone number is (571)272-6851. The examiner can normally be reached on M-TH 7:00-16:00, F 7:00-11:00(Eastern).
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/J.A.T./Examiner, Art Unit 3791
/TSE W CHEN/Supervisory Patent Examiner, Art Unit 3791