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 amendments filed 20 March 2026 have been entered. Claims 1 – 18, 20 – 21, and 23 - 25 are pending. Applicant’s amendments have overcome each and every rejection under 35 U.S.C. 112 previously applied in the office action dated 20 October 2025. The IDS for 8/13/2024 has been considered, updated, and signed regarding the Hu reference.
Claim Interpretation
Applicant has not made an amendment regarding the 112(f) Claim Interpretations applied in the Office Action dated 20 October 2025, so the interpretation detailed in the Office Action dated 20 October 2025 is maintained for the term “a means for driving fluid flow through the detection membrane to obtain a biological measurement” in Claim 3.
Claim Objections
Claims 24 and 25 are objected to because of the following informalities: regarding the term “The device of claim 21”, it is suggested to revise the term to be “The mixing device of claim 21” for consistency and readability in the claims. 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 – 18, 20 - 21 and 23 - 25 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 the term “the self-collection device”. There is insufficient antecedent basis for this limitation in the claim. It is unclear if this is intended to be the same as the “self-collection and processing device” previously-recited in the claim. For the purposes of examination, the term “the self-collection device” is deemed to claim “the self-collection and processing device”. Claims 2 – 18, 20, and 23 – 25 are similarly rejected due to their dependence on Claim 1.
Claims 2 – 12 each recite “the device of claim 1” (or do their respective dependencies originating from claim 1). It is unclear if this is intended to be the same as the “self-collection and processing device” or the “self-collection device” previously-recited in claim 1. Based on the interpretation above, for the purposes of examination, the term “the device of” is deemed to claim “the self-collection and processing device”.
Claim 5 recites the term “wherein the reservoir membrane is removed after the biological reagent is introduced to the biofluid”, which recites an active method step within an apparatus claim. As such, it the statutory category of the claim is unclear. For the purposes of examination, the term “wherein the reservoir membrane is removed after the biological reagent is introduced to the biofluid” is deemed to claim “wherein the reservoir membrane is configured to be removed after the biological reagent is introduced to the biofluid”.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation “a vertical flow immunoassay (VFI) and/or a lateral flow assay (LFA) integrated with the reservoir membrane or the biomarker detection membrane”, and the claim also recites “wherein the biomarker detection membrane comprises a VFI or LFA membrane”, which is the narrower statement of the range/limitation. That latter membrane word potentially only applies to LFA and not VFI. Then the broad limitation that that there is either a VFI or an LFA that can comprise a biomarker detection membrane, but then the narrow limitation is that biomarker detection membrane now comprises a VFI. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For the purposes of examination, the term “a vertical flow immunoassay (VFI) and/or a lateral flow assay (LFA) integrated with the reservoir membrane or the biomarker detection membrane, wherein the biomarker detection membrane comprises a VFI or LFA membrane including: one or more biomarker detection elements” is deemed to claim “a vertical flow immunoassay (VFI) or a lateral flow assay (LFA) integrated with the reservoir membrane or the biomarker detection membrane, wherein the biomarker detection membrane comprises one or more biomarker detection elements.” Claim 10 is similarly rejected due to its dependence on Claim 9.
Claim 10 recites the term “wherein the device is configured” in line 5. It is unclear if this is intended to be the same device as the previously-recited “self-collection and processing device”. For the purposes of examination, the term “wherein the device is configured” is deemed to claim “wherein the self-collection and processing device is configured.”
Claim 13 recites the term “providing the device of claim 1” in line 3. It is unclear if this is intended to be the same as the “self-collection and processing device” or the “self-collection device” previously-recited in claim 1. Based on the interpretation above, for the purposes of examination, the term “the device of” is deemed to claim “providing the self-collection and processing device of claim 1”.
Claim 18 recites the term “an array of detection spots or an array of detection spots including an array for multiplex detection of a plurality of unique biomarkers, and a positive control.” The metes and bounds of the claim are unclear because it is unclear how “an array of detection spots” and “an array of detection spots” is intended to differ. The second array appears to also include another “array”, so it is unclear if the second set is intended to be a larger array, or potentially just more specialized. For the purposes of examination, the term “an array of detection spots or an array of detection spots including an array for multiplex detection of a plurality of unique biomarkers, and a positive control” is deemed to claim “an array of detection spots or a multiple detection array of detection spots for multiplex detection of a plurality of unique biomarkers, and a positive control.
Claim 21 recites the term “a biomarker detection membrane configured to connect to the cap after the reservoir membrane is removed to detect one or more biomarkers in the biofluid” in lines 11 – 12. There is insufficient antecedent basis for this limitation in the claim. There is no previously-recited reservoir membrane. In the context of the rest of the claim, the only other “removal” of the reservoir membrane appears to be a broad interpretation of “configured to pierce the reservoir membrane to fluid” limitation in lines 16 - 17, which “removes” its coverage of the collection tube. As such, for the purposes of examination, the term “a biomarker detection membrane configured to connect to the cap after the reservoir membrane is removed to detect one or more biomarkers in the biofluid” is deemed to be recited at the end of the claim after the “the tube insert piecing end is configured to…in the cap reservoir” limitation. Claims 24 and 25 are similarly rejected due to their dependence on Claim 21.
Claim 21 recites the terms “one or more biomarkers in the biofluid” and “contact the biofluid in the collection tube” in lines 12 and 17. There is insufficient antecedent basis for the first “biofluid” limitation in the claim. Overall, it is unclear if these biofluids are intended to be the same or different than the previously-recited “fluid sample”. For the purposes of examination, the terms “one or more biomarkers in the biofluid” and “contact the biofluid in the collection tube” are deemed to claim “one or more biomarkers in the fluid sample” and “contact the fluid sample in the collection tube.” Similarly, given the interpretation of the term as “the fluid sample”, the term “the biofluid” in Claim 25 is also deemed to claim “the fluid sample”. Claims 24 and 25 are similarly rejected due to their dependence on Claim 21.
Claim 24 recites the term “wherein the fluid collection tube” in lines 1 - 2. There is insufficient antecedent basis for this limitation in the claim. There is no previously-recited fluid collection tube. For the purposes of examination, the term “wherein the fluid collection tube” is deemed to claim “wherein the collection tube”.
Claim 23 recites the term “The device of claim 13, wherein the reservoir membrane is removed after the biological reagent is introduced to the biofluid in the collection tube”. It is unclear what statutory category this claim is intended to be, as it depends from “the device of claim 13”, which appears to be “the device of claim 1”, as recited in Claim 13. As such, it appears that the limitation “wherein the reservoir membrane is removed…in the collection tube” is functional language regarding the capabilities of the device. For the purposes of examination, the term “The device of claim 13, wherein the reservoir membrane is removed after the biological reagent is introduced to the biofluid in the collection tube” is deemed to claim, “The self-collection and processing device of claim 1, wherein the reservoir membrane is removed after the biological reagent is introduced to the biofluid in the collection tube”, since the device of claim 1 is the device recited in Claim 13.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 – 5, 13, 16, 21, and 23 - 25 are rejected under 35 U.S.C. 103 as being unpatentable over Skakoon (United States Patent Application Publication US 2012/0046574 A1), hereinafter Skakoon, in view of Mayer.
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Figure A: Examiner-Annotated Skakoon Figure 7A with Figure 8, showing removable feature 720 (“seal cap 720”) and removable feature 802 (“housing 802”) as collectively a cap for collection tube feature 702 (“collection vessel 702”)
Regarding Claim 1, Skakoon discloses
A self-collection and processing device for collecting and processing of a biofluid that may contain a biological specimen or a biomarker of the biological specimen from a user ([Abstract]; [0003], Fig 7A, Fig 8) the self-collection device comprising:
a mouthpiece (Fig 7, “mouthpiece 706”, [0085]);
a collection tube fluidically connected to the mouthpiece (Fig 7, [0085] “saliva inlet 710” to “collection vessel 702”);
a cap (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Fig 7A, Fig 8)(Examiner notes that both the “housing 802” and the “seal cap 720” are removable from the “collection vessel 702” portion (cap shown removed in Fig 7A), and when they are both in place, they collectively are a "cap" for the “collection vessel 702”) configured to connect to the collection tube (Figure 7 “seal cap 720” attached to “collection vessel 702”; [0086] “seal cap 720, which allows access to the collected saliva in collection vessel 702”; Figure 8, “housing 802” attached to “collection vessel 702”; [0087] “inserted into housing 802”) and fluidically seal the collection tube from a surrounding environment (Fig 7, “seal cap 720”; [0086] “seal cap 720, which allows access to the collected saliva in collection vessel 702…can be removed…after a successful saliva donation”; Figure 8, “housing 802” attached to “collection vessel 702”; [0087] “inserted into housing 802”)(Examiner notes that before the “seal cap 720” is removed, it is sealing the contents of the collection tube from letting saliva flow outside of the tube. Examiner further notes that when “housing 802” is attached, it also seals the collection tube from letting saliva leak outside of the environment outside of the collective assembly.), wherein the cap comprises:
an integrated reservoir (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Figure 8; [0087] “inserted into housing 802”)(Examiner notes that the interior of the collective cap of “seal cap 720” + “housing 802” is broadly a reservoir, defined by Merriam-Webster as “ a place where something is kept in store”. The “housing 802” portion includes a place that stores the lateral flow assay strips.) configured to hold a biological reagent ([0087] “test strips 804…lateral flow immunoassay”)(Examiner notes that an “immunoassay” is broadly defined by Merriam-Webster as “a technique or test used to detect the presence or quantity of a substance (such as a protein) based on its capacity to act as an antigen.” The “antigen” is a biological reagent.) configured for use with the biological specimen in the collection tube ([0087] “saliva collection device 700…inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva.”);
a reservoir membrane (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; [0086] “alternatives to seal cap 720 to allow access to the collected saliva exist, and include a puncturable septum similar to a medicament vial with a rubber closure…a peelable or puncturable, sealed-foil covering…) to contain the biological reagent in the integrated reservoir and to temporarily seal the integrated reservoir from the collection tube ([0086] “…a peelable or puncturable, sealed-foil covering…”; Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”)(Examiner notes that the reservoir is sealed from the collection tube if the tube is inserted and is unpunctured, but it is temporary, as it can be punctured allowing the portions to interact. The biological reagent is contained in the integrated reservoir and cannot reach the contents of the collection tube while the immunoassay strip is in the “housing 802” and the tube seal is sealed.);
a biomarker detection membrane ([0087] “lateral flow immunoassay test strips…”) configured to connect to the cap ([0087] “lateral flow immunoassay test strips…” are a part of the collective Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”)(Examiner notes that the test strips are a part of the “seal cap 720” + “housing 802” overall cap at all times after manufacturing, so they are also functionally connected to the cap after the reservoir membrane is removed.) after the reservoir membrane is removed ([0086] “…seal cap 720 can be removed as shown in FIG. 7A after a successful saliva donation...peelable or puncturable, sealed-foil covering”; Fig 7A) to detect one or more biomarkers in the biofluid ([0087] “…saliva collection device 700…is inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva”; [0087] “…methodology and reading of results is performed…normal practice for lateral flow immunoassay strip use”.)(Examiner notes that lateral immunoassay test strips are used to broadly detect one or more biomarkers in biofluid in their “normal practice for lateral flow immunoassay strip use”.)
Skakoon does not specifically disclose a tube insert positioned in the collection tube, wherein the tube insert includes: a piercing end; wherein the tube insert piercing end is configured to pierce the reservoir membrane and fluidically contact the biofluid in the collection tube and the biological reagent) in the cap reservoir.
Mayer teaches device and methods for collecting a liquid specimen (such as saliva) from a subject with a swab as an insert to a tube, which can penetrate a membrane on a sample reagent chamber to combine the sample with the reagent within the enclosed assembly. Specifically for Claim 1, Mayer teaches a reservoir membrane (Fig 3B, Top of solution chamber 320”; [0051] “solution chamber…constructed of a material capable of being destructively deformed (e.g., glass, or plastic).“) to contain the biological reagent in the integrated reservoir ([0051] “… solution can include, but is not limited to, a buffer, or a reagent suspension.”; Fig 3B [0072] “solution chamber”) and to temporarily seal the integrated reservoir ([0072] “solution chamber”) from the collection tube (Fig 3B; “sheath 302 of the collection device 300…swab 310”; [0072] “the solution chamber can remain sealed until the user operates the optional element 320 to the fully attached arrangement.”)(Examiner notes that the collection swab with the fluid sample is within the tube “sheath 302”)
a tube insert (Fig 3A – 3C; [0072] “shaft 308”) positioned in the collection tube (Fig 3A – 3C “affixed shaft 308 and swab 310” within “sheath 302; [0073] “affixed shaft 308 and swab 310”) wherein the tube insert comprises: a piercing end (Fig 3A; “swab 310” on “shaft 308”; [0072] “Similarly to Fig 2C, the optional element 320 can include a partially or fully attached arrangement…user operates the optional element 320 to the fully attached arrangement. The solution chamber can then be pierced…”; Regarding Fig 2C--[0068] – [0069] “the fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220…”); wherein the tube insert piercing end is configured to pierce the reservoir membrane and fluidically contact the biofluid in the collection tube and the biological reagent ([0051] “… solution can include, but is not limited to, a buffer, or a reagent suspension.”; ([0010] “material specimen can include saliva, urine, blood, or serum of a person...”; [0069] “allow the solution to mix with the sample…”) in the cap reservoir ([0072] “Similarly to Fig 2C, the optional element 320 can include a partially or fully attached arrangement…user operates the optional element 320 to the fully attached arrangement. The solution chamber can then be pierced…”; Regarding Fig 2C--[0068] – [0069] “the fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220…”)
Skakoon and Mayer both disclose and teach tubes that have saliva sample collected within them, and that include an upper portion (with the sample) that is inserted into a bottom portion receptacle (with the reagent) to combine the biological sample with a reagent for test processing: Skakoon (saliva sample in upper tube inserted into a “housing” receptacle with immunoassay test cards) and Mayer (Saliva sample-carrying swab in a tube inserted into a bottom receptacle “solution chamber”) provides a motivation to combine at [0070] with “The fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220 and allow the solution to mix with the sample within the sheath 202.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that having an all-in-one attached implement to allow for the sample and reagent to mix in a single unit without spilling or wasting the sample or reagent (which is a concern with loading a reagent and/or sample onto a card with a dropper or separate component).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine Skakoon’s disclosed saliva mouthpiece and tube assembly that can be pierced and plugged into a housing component to form a liquid connection between saliva samples and flow immunoassay test cards with Mayer’s taught tube insert to pierce the membrane holding the test reagent when the tube is connected, creating a single all-in-one saliva sampling tube-shaped device that can pierce a membrane while it is inserted into the test card housing to let saliva flow onto a test card, minimizing possibilities of lost sample through leakage.
Regarding Claim 21, Skakoon discloses
A mixing device for mixing two separate fluid components ([Abstract]; [0003], Fig 7A, Fig 8; [0052] “test reagents can be added…”; [0053] “a saliva sample…immunoassay strips…”; [0054] “…saliva…be allowed to enter the assaying portion”) comprising:
a collection tube (Fig 7, [0085] “saliva inlet 710” to “collection vessel 702”) for containing a fluid sample ([0086] “…collected saliva in collection vessel 702…”)
a cap (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Fig 7A, Fig 8)(Examiner notes that both the “housing 802” and the “seal cap 720” are removable from the “collection vessel 702” portion (cap shown removed in Fig 7A), and when they are both in place, they collectively are a "cap" for the “collection vessel 702”) configured to connect to the collection tube (Figure 7 “seal cap 720” attached to “collection vessel 702”; [0086] “seal cap 720, which allows access to the collected saliva in collection vessel 702”; Figure 8, “housing 802” attached to “collection vessel 702”; [0087] “inserted into housing 802”) and fluidically seal the collection tube from a surrounding environment (Fig 7, “seal cap 720”; [0086] “seal cap 720, which allows access to the collected saliva in collection vessel 702…can be removed…after a successful saliva donation”; Figure 8, “housing 802” attached to “collection vessel 702”; [0087] “inserted into housing 802”)(Examiner notes that before the “seal cap 720” is removed, it is sealing the contents of the collection tube from letting saliva flow outside of the tube. Examiner further notes that when “housing 802” is attached, it also seals the collection tube from letting saliva leak outside of the environment outside of the collective assembly.), wherein the cap comprises:
an integrated reservoir (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Figure 8; [0087] “inserted into housing 802”)(Examiner notes that the interior of the collective cap of “seal cap 720” + “housing 802” is broadly a reservoir, defined by Merriam-Webster as “ a place where something is kept in store”. The “housing 802” portion includes a place that stores the lateral flow assay strips.) configured to hold a sample reagent ([0087] “test strips 804…lateral flow immunoassay”)(Examiner notes that an “immunoassay” is broadly defined by Merriam-Webster as “a technique or test used to detect the presence or quantity of a substance (such as a protein) based on its capacity to act as an antigen.” The “antigen” is a biological reagent.) configured for use with the fluid sample in the collection tube ([0087] “saliva collection device 700…inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva.”);
a biomarker detection membrane ([0087] “lateral flow immunoassay test strips…”) configured to connect to the cap ([0087] “lateral flow immunoassay test strips…” are a part of the collective Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”)(Examiner notes that the test strips are a part of the “seal cap 720” + “housing 802” overall cap at all times after manufacturing, so they are also functionally connected to the cap after the reservoir membrane is removed.) after the reservoir membrane is removed ([0086] “…seal cap 720 can be removed as shown in FIG. 7A after a successful saliva donation...peelable or puncturable, sealed-foil covering”; Fig 7A) to detect one or more biomarkers in the biofluid ([0087] “…saliva collection device 700…is inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva”; [0087] “…methodology and reading of results is performed…normal practice for lateral flow immunoassay strip use”.)(Examiner notes that lateral immunoassay test strips are used to broadly detect one or more biomarkers in biofluid in their “normal practice for lateral flow immunoassay strip use”.)
a reservoir membrane (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; [0086] “alternatives to seal cap 720 to allow access to the collected saliva exist, and include a puncturable septum similar to a medicament vial with a rubber closure…a peelable or puncturable, sealed-foil covering…”) to seal the reservoir from the collection tube ([0086] “…a peelable or puncturable, sealed-foil covering…”; Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”)(Examiner notes that the reservoir is sealed from the collection tube if the tube is inserted and is unpunctured, but it is temporary, as it can be punctured allowing the portions to interact. The biological reagent is contained in the integrated reservoir and cannot reach the contents of the collection tube while the immunoassay strip is in the “housing 802” and the tube seal is sealed.);
Skakoon does not specifically disclose for mixing two separate fluid components; a tube insert positioned in the collection tube, wherein the tube insert comprises: a piercing end; wherein the tube insert piercing end is configured to pierce the reservoir membrane and fluidically contact the fluid sample in the collection tube and the sample reagent in the cap reservoir.
Mayer teaches for mixing two separate fluid components ([0070] “sample/solution mixture”; [0005] “reagent solution”; [0010] “material specimen can include saliva, urine, blood, or serum of a person.”); a reservoir membrane (Fig 3B, Top of solution chamber 320”; [0051] “solution chamber…constructed of a material capable of being destructively deformed (e.g., glass, or plastic).“) to contain the biological reagent in the integrated reservoir ([0051] “… solution can include, but is not limited to, a buffer, or a reagent suspension.”; Fig 3B [0072] “solution chamber”) and to temporarily seal the integrated reservoir ([0072] “solution chamber”) from the collection tube (Fig 3B; “sheath 302 of the collection device 300…swab 310”; [0072] “the solution chamber can remain sealed until the user operates the optional element 320 to the fully attached arrangement.”)(Examiner notes that the collection swab with the fluid sample is within the tube “sheath 302”)
a tube insert (Fig 3A – 3C; [0072] “shaft 308”) positioned in the collection tube (Fig 3A – 3C “affixed shaft 308 and swab 310” within “sheath 302; [0073] “affixed shaft 308 and swab 310”) wherein the tube insert comprises: a piercing end (Fig 3A; “swab 310” on “shaft 308”; [0072] “Similarly to Fig 2C, the optional element 320 can include a partially or fully attached arrangement…user operates the optional element 320 to the fully attached arrangement. The solution chamber can then be pierced…”; Regarding Fig 2C--[0068] – [0069] “the fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220…”); wherein the tube insert piercing end is configured to pierce the reservoir membrane and fluidically contact the biofluid (fluid sample in Claim 21) in the collection tube and the biological reagent (sample reagent in Claim 21) ([0051] “… solution can include, but is not limited to, a buffer, or a reagent suspension.”; ([0010] “material specimen can include saliva, urine, blood, or serum of a person...”; [0069] “allow the solution to mix with the sample…”) in the cap reservoir ([0072] “Similarly to Fig 2C, the optional element 320 can include a partially or fully attached arrangement…user operates the optional element 320 to the fully attached arrangement. The solution chamber can then be pierced…”; Regarding Fig 2C--[0068] – [0069] “the fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220…”)
The motivation to for Claim 21 to combine Skakoon and Mayer is the same as that described in more detail above for Claim 1. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine Skakoon’s disclosed saliva mouthpiece and tube assembly that can be pierced and plugged into a housing component to form a liquid connection between saliva samples and flow immunoassay test cards with Mayer’s taught tube insert to pierce the membrane holding the test reagent when the tube is connected, creating a single all-in-one saliva sampling tube-shaped device that can pierce a membrane while it is inserted into the test card housing to let saliva flow onto a test card, minimizing possibilities of lost sample through leakage.
Regarding Claim 2, Skakoon in view of Mayer discloses as described above, The device of claim 1. For the remainder of Claim 2, Skakoon discloses a positioning feature to align and position (Fig 8, circular alignment slot for “saliva collection device 700” inserted in “housing 802”; [0087] “…saliva collection device 700…is inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva”)(Examiner notes that the detection membrane is the “test strip(s) 804”, and the “fluid connection” detection interface is facilitated by the “saliva collection device 700” to “housing 802”’s alignment and positioning to preserve the alignment and connection between sample and the detection membrane)
Skakoon does not disclose wherein the tube insert further comprises a positioning feature to align and position the piercing end at a pre-determined distance from the reservoir membrane.
Mayer teaches wherein the tube insert (Fig 3A – 3C; [0072] “shaft 308”) further comprises a positioning feature to align and position the piercing end at a pre-determined distance from the reservoir membrane (Fig 3A and 3B; [0072] “…the optional element 320 can be an extensible portion of the sheath 302 to allow for varying lengths of shaft 308…can include the solution chamber of the collection device 300. Similarly to Fig 2C, the optional element 320 can include a partially or fully attached arrangement where the solution chamber can remain sealed until the user operates the optional element 320 to the fully attached arrangement. The solution chamber can then be pierced and the sample mixed with the solution”; Regarding Fig 2C--[0068] – [0069] “the fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220 and allow the solution to mix with the sample within the sheath 202.”)(Examiner notes that the tip is held at a distance above the membrane until the piercing element can be depressed into the membrane by pressing the “optional element 320”.):
Skakoon and Mayer both disclose and teach tubes that have saliva sample collected within them, and that include an upper portion (with the sample) that is inserted into a bottom portion receptacle (with the reagent) to combine the biological sample with a reagent for test processing: Skakoon (saliva sample in upper tube inserted into a “housing” receptacle with immunoassay test cards) and Mayer (Saliva sample-carrying swab in a tube inserted into a bottom receptacle “solution chamber”) Mayer provides a motivation to combine at [0069] with “The fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220 and allow the solution to mix with the sample within the sheath 202.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that aligning a piercing end with a membrane would allow for consistent perforation of the membrane when the portions of the device are connected to each other.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine Skakoon’s disclosed tube assembly connecting into a round receptable on a housing containing a flow immunoassay with Mayer’s taught swab member aligned in the tube such that it is centered to pierce a membrane on a round receptacle (containing sample reagent), creating a single device that reliably punctures a membrane to connect a saliva sample with testing components.
Regarding Claim 3, Skakoon in view of Mayer discloses as described above, The device of claim 1. For the remainder of Claim 3, Skakoon discloses further comprising:
a means for driving fluid flow through the biomarker detection membrane to obtain a biological measurement ([0087] “lateral flow immunoassay test strips”,“…saliva collection device 700…is inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva”)(Examiner notes that the fluid flow goes laterally through a “lateral flow immunoassay” as the fluid is absorbed on the strip during the “fluid connection” with the sample. The immunoassay strip membrane drives fluid flow through itself with wicking action in the material); and
a holder for holding the biomarker detection membrane (Fig 8, “test housing 802” shown holding six “test strips 804”).
Regarding Claim 4, Skakoon in view of Mayer discloses as described above, The device of claim 1. For the remainder of Claim 4, Skakoon discloses wherein the reservoir membrane is a re-sealable membrane ([0086] “seal cap 720 can be removed…a peelable or puncturable, sealed-foil covering”)(Examiner notes that “re-sealable” is defined in Applicant’s specification at [0015] as “The re-sealable membrane may comprise an interchangeable adhesive layer…” and “re-sealable is used broadly herein to refer to a membrane than can be removed and replaced without sacrificing device accuracy or reliability” The foil membrane is part of peelable “seal cap” and is capable of being replaced with a different adhesive “peelable” foil piece.).
Regarding Claim 5, Claim 23, and Claim 25, Skakoon in view of Mayer discloses as described above, The device of claim 1, (See the 112b interpretation above for Claim 23 relative to the dependency with the device within the method claim and statutory category lack of clarity), and The device of claim 21, respectively. For the remainder of Claims 5, 23, and 25, Skakoon discloses wherein the reservoir membrane is removed after the biological reagent is introduced to the biofluid in the collection tube ([0086] “..peelable or puncturable, sealed-foil covering”; ([0087] “…saliva collection device 700…is inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva”)(Examiner notes that puncturing the membrane is sufficient to allow the sample to flow and contact the test strips with the saliva collection device inserted into housing 802. The sealed-foil covering is also configured such that the peelable foil covering could be peeled-off and removed after it has been punctured, by removing the saliva collection device from the housing and peeling the foil covering after the sample fluid has contacted the test strip. Examiner further notes that this recitation just requires that the reservoir membrane is functionally able to be removed as part of the functionally-claimed capabilities of the devices.).
Regarding Claim 13, Skakoon in view of Mayer discloses providing the device of claim 1 (See citation in Claim 1). For the remainder of Claim 13, Skakoon discloses A method for self-collecting and processing a biofluid ([Abstract]), the method comprising the steps of:
introducing the biofluid into the collection tube by the mouthpiece ([0074] “Saliva, driven by the donor's spitting action and blowing action, enters saliva inlet 110 of mouthpiece 106.”; [0085] “…Mouthpiece 706 includes a saliva inlet 710”);
connecting the cap (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Fig 7A, Fig 8) to the collection tube (Figure 7 “seal cap 720” attached to “collection vessel 702”; [0086] “seal cap 720, which allows access to the collected saliva in collection vessel 702”; Figure 8, “housing 802” attached to “collection vessel 702”; [0087] “inserted into housing 802”);
mixing the biofluid with the biological reagent to obtain a mixture of biofluid and biological reagent, thereby self-collecting and processing the biofluid ([0087] “saliva collection device 700…inserted into housing 802, which causes a fluid connection allowing test strips 804 to be exposed to saliva.”);,.
Skakoon does not particularly disclose thereby piercing the reservoir membrane with the piercing end of the tube insert and mixing the biofluid with the biological reagent to obtain a mixture of biofuid and biological reagent, thereby self-collecting and processing the biofluid.
Mayer teaches thereby piercing the reservoir membrane with the piercing end of the tube insert and mixing the biofluid with the biological reagent to obtain a mixture of biofuid and biological reagent, thereby self-collecting and processing the biofluid ([0068] – [0069] “the fully attached arrangement, for example, can cause the tip of the swab 210 to puncture the solution chamber 206 within the optional module 220 and allow the solution to mix with the sample within the sheath 202.…”; [0003] “facilitate self-collection of biological specimens…specimen migrates to and reacts with reagents…a test result can be indicated to the user...”)
The motivation for Claim 13 to combine Skakoon with Mayer is the same as that described in more detail in Claim 1. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine Skakoon’s disclosed saliva mouthpiece and tube assembly that can be pierced and plugged into a housing component to forma liquid connection between saliva samples and flow immunoassay test cards with Mayer’s taught tube insert to pierce the membrane holding the test reagent when the tube is connected, creating a single all-in-one saliva sampling tube-shaped device that can pierce a membrane while it is inserted into the test card housing to let saliva flow onto a test card, minimizing possibilities of lost sample through leakage.
Regarding Claim 16, Skakoon in view of Mayer discloses as described above, The method of claim 13. For the remainder of Claim 16, Skakoon does not specifically disclose wherein the tube insert is positioned in the collection tube before the step of introducing the biofluid into the collection tube.
Mayer teaches wherein the tube insert (Fig 3A – 3C; [0072] “shaft 308”) is positioned in the collection tube before the step of introducing the biofluid into the collection tube (Fig 3; [0022] “…swab and shaft removed…removable sheath and tip element”; FIG. 2B shows the collection device 200 with the sheath 202 removed from the handling area 204…exposing the shaft 208 and the swab 210. The specimen can be collected with the exposed swab 210 and the sheath 202 reaffixed to the handling area to protect the integrity of the collected specimen.”; [0073] “The optional element 330 of FIG. 3B can be an actuator for the unsealing of one or more solution chambers.”)(Examiner notes that the “shaft 308” with the exposed swab end can be inserted and removed from the sheath at will. As the “integrity of the collected specimen” is intended to be protected, a person with ordinary skill in the art would place the swab in the sheath collection tube to keep it clean, without depressing the “element 330” button that punctures the chamber at the bottom.)
Skakoon provides a motivation to combine at [0055] with “device for which the donor may decouple from and recouple to the device without substantial loss of any accumulated Saliva,” and Mayer provides a similar motivation to combine at [0022] with “The specimen can be collected with the exposed swab 210 and the sheath 202 reaffixed to the handling area to protect the integrity of the collected specimen.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that a feature capable of coupling and recoupling the sample chamber would allow for the chamber to be closed before and after saliva collection, providing protection from contamination for the saliva samples therein.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the disclosed saliva mouthpiece and tube assembly that can be removably attached with Mayer’s taught swab insert assembly that can be removably attached, creating a single saliva sampling tube device with an insert that can be inside the tube prior to (and after) saliva sample collection, protecting the sample collection mechanism from contamination before (and during) testing.
Regarding Claim 24, Skakoon discloses further comprising a mouthpiece (Fig 7, “mouthpiece 706”, [0085]), wherein the fluid collection tube is fluidically connected to the mouthpiece (Fig 7, [0085] “saliva inlet 710” to “collection vessel 702”).
Claims 6 - 8 are rejected under 35 U.S.C. 103 as being unpatentable over Skakoon in view of Mayer, further in view of Chen et. al., “Paper-based Vertical Flow Immunoassay (VFI) for detection of bio-threat pathogens”, hereinafter Chen.
Regarding Claim 6, Skakoon in view of Mayer discloses as described above, The device of claim 4. For the remainder of Claim 6, Skakoon discloses wherein the re-sealable membrane comprises:
an interchangeable adhesive layer ([0086] “seal cap 720 can be removed…a peelable or puncturable, sealed-foil covering”, “Alternatives to removable seal cap 720 to allow access to the collected saliva…puncturable septum…rubber closure…needle less connector…Luer taper fitting…removable plus…frangible tip that can be snapped off…peelable or puncturable, sealed-foil covering”)(Examiner notes that “re-sealable” is defined in Applicant’s specification at [0015] as “The re-sealable membrane may comprise an interchangeable adhesive layer…” and “re-sealable is used broadly herein to refer to a membrane than can be removed and replaced without sacrificing device accuracy or reliability” The foil membrane is part of peelable “seal cap” and is capable of being interchangeable with a different adhesive “peelable” foil pieces, or functionally interchangeable with other end cap fitting types, like the Luer taper fitting with a removable plug. ).
Skakoon does not disclose comprises a porous substrate comprising a plurality of biomarker detectors.
Chen teaches a vertical flow immunoassay (VFI) for detection of bio-threat pathogens, wherein the VFI is a round, flat form factor that fits in an o-ring-secured cap assembly on the end of a sample delivery tube. Specifically for Claim 6, Chen teaches and a porous substrate comprising a plurality of biomarker detectors ([Fig. 2.,[Page 83, Fig 2 Caption] “(A) Apparatus of the VFI platform: a nitrocellulose membrane encapsulated in a stainless steel filter holder…”; [Page 82, Right Column, Paragraph 1] “Fig 1(a) illustrates…immune-biosensor implemented in a porous paper membrane in the vertical flow format”; [Page 82, Right Column, Paragraph 2] “…internal surface of the porous structure is coated with capture antibody”; [Page 85, Left Column, Bottom] with “With the ability to accommodate a microarray utilizing different capture antibodies…multiplex biomarker detection.”)).
Skakoon and Chen both teach a membrane that is in the fluid path of sample from a tube, Skakoon’s membrane the “peelable or puncturable sealed-foil membrane” of the “seal cap”, and Chen’s the circular porous VFI membrane secured to the a tube with a stainless steel cap assembly. Chen provides a motivation to combine at [Page 85, Left Column, Bottom] with “With the ability to accommodate a microarray utilizing different capture antibodies, VFI is inherently suitable for multiplex biomarker detection.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that combining the membrane in contact with the sample with vertical flow immunoassay would allow for multiplex testing of the sample as it flows through the tube to the bottom chamber, (a fluid path already present in Skakoon’s disclosure). It would have been predictable to use immunoassay with biomarker detectors in any similar flow-through tube with saliva samples. In combination with Skakoon, the fluid path for the saliva would continue to be from the upper part of the tube, through a membrane that temporarily separates the saliva from the housing chamber, to the lower “housing” chamber.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the “peelable or puncturable sealed-foil membrane” of the “seal cap” in the flow path for the sample from the upper part of the tube to the exit into the test chamber disclosed in Skakoon with Chen’s taught VFI membrane in the flow path from the upper part of a tube to an exit, creating a single saliva testing device for multiplex testing of analytes using in-line VFI in the tube.
Regarding Claim 7, Skakoon in view of Mayer, further in view of Chen discloses as described above, The device of claim 6. For the remainder of Claim 7, Skakoon does not specifically disclose wherein the plurality of biomarker detectors are selected from the group consisting of: polynucleotides, polypeptides, antibodies, nucleic acids, toxins, bacteria, virus, biological vesicles.
Chen teaches wherein the plurality of biomarker detectors are selected from the group consisting of: polynucleotides, polypeptides, antibodies ([Page 82, Right Column, Paragraph 2] “..porous structure is coated with capture antibody”; [Page 85, Left Column, Bottom] with “With the ability to accommodate a microarray utilizing different capture antibodies…multiplex biomarker detection.”) nucleic acids, toxins, bacteria, virus, biological vesicles.
Skakoon provides a motivation to combine at [0087] with “Test methodology and reading of results is performed in accordance with normal practice for lateral flow immunoassay test strip use.“ Chen provides a motivation to combine at [Page 82, Left Column, Bottom] – [Page 82, Right Column, 1st Full paragraph] ”Detection of the C. pseudomallei…based on a sandwich immunoassay targeting the capsular polysaccharide (CPS)…antibody to be used for capture and detection of CPS.” A person having ordinary skill in the art would recognize that a generic “immunoassay test strip” as disclosed in Skakoon in view of Mayer, further in view of Chen could work by including the biomarkers that are specifically different capture antibodies, which would be useful for reacting to (and detecting) a plurality of specific targets in samples, like CPS.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the broadly-described “immunoassay membrane” disclosed by Skakoon in view of Mayer, further in view of Chen with Chen’s taught biomarker detectors such as antibodies, creating a single saliva testing device that used immunoassay test membranes with antibody detector regions to detect a plurality of antigens in saliva.
Regarding Claim 8, Skakoon in view of Mayer, further in view of Chen discloses as described above, The device of claim 6. For the remainder of Claim 8, Skakoon does not disclose wherein the plurality of biomarker detectors comprise a plurality of unique biomarker detectors arranged in a microarray on the biomarker detection membrane for multiplex detection of biomarkers in the biofluid.
Chen teaches wherein the plurality of biomarker detectors ([Page 85, Left Column, Bottom] with “With the ability to accommodate a microarray utilizing different capture antibodies…multiplex biomarker detection.”) comprise a plurality of unique biomarker detectors arranged in a microarray on the biomarker detection membrane for multiplex detection of biomarkers in the biofluid (Figure 6, “Multiplexing VFI… (A) Design of the microarray of the multiplexing VFI membrane for CPS and PGA”; [Page 85, Right Column, Top] “platform to detect two bio-threat targets simultaneously, i.e. CPS and PGA (a biomarker for the bacterium Bacillus anthracis, which is the causative agent of anthrax)”)
Chen teaches a motivation to combine at [Page 85, Right Column] with “VFI platform to detect two bio-threat targets simultaneously.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that the coating on the lateral flow immunoassay could be used to show the presence of multiple analytes at the same time, which would be useful for determining results quickly and clearly. It would have been predictable to use the microarrays deposited for multiplex detection of analytes taught by Chen on any similar vertical flow immunoassay test membrane, as it would continue to operate with the function of detecting analytes using a vertical flow immunoassay test strip.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the vertical flow immunoassay membrane disclosed in Skakoon in view of Mayer further in view of Chen with the with the microarrays for multiplex detection deposited on a vertical flow immunoassay membrane taught by Chen, creating a single saliva testing device that shows results for multiple analytes in a single test in its immunoassay.
Claims 9 – 10, 14 – 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Skakoon in view of Mayer, further in view of Koczula, et. al., “Lateral flow assays”, hereinafter Koczula.
Regarding Claim 9, Skakoon in view of Mayer discloses as described above, The device of claim 1. For the remainder of Claim 9, Skakoon discloses a vertical flow immunoassay (VFI) and/or a lateral flow assay (LFA) (Fig 8, [0087] “plurality of lateral flow immunoassay test strips 804 internal to test housing 802…”) integrated with (Fig 8, [0087] “…internal to test housing 802”) the reservoir membrane or the biomarker detection membrane (Fig 8, [0087] “…lateral flow immunoassay test strips 804 internal to test housing 802”),
wherein the biomarker detection membrane comprises a VFI or LFA membrane ([0087] “lateral flow immunoassay test strips”)(Examiner notes that the test strips are membranes.)
Skakoon does not specifically disclose comprising one or more biomarker detection elements or one or more biomarker detection elements comprising antibodies.
Koczula teaches comprising one or more biomarker detection elements {Fig 1, [Page 111, Paragraph 3] “This review focuses on ”lateral flow immunoassays’ (LFIAs), in which antibodies are exclusively used as recognition elements”), or one or more biomarker detection elements comprising antibodies (Fig 1, [Page 111, Paragraph 3] “… ”lateral flow immunoassays’ (LFIAs), in which antibodies…used as recognition elements”),
The motivation for Claim 9 to combine Skakoon in view of Mayer with Koczula is the same as that described in more detail in Claim 7. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the broadly-described “lateral flow immunoassay test strips” disclosed by Skakoon with Koczula’s taught lateral flow immunoassay test strips with biomarker detectors such as antibodies, creating a single saliva testing device that used immunoassay test strips with antibody biomarker detector regions to detect antigens in saliva.
Regarding Claim 10, Skakoon in view of Mayer discloses as described above, The device of claim 9. For the remainder of Claim 10, the vertical flow immunoassay comprises:, Claim 9 (from which this claim depends) recites “further comprising a vertical flow immunoassay (VFA) and/or a lateral flow assay (LFA).” The limitations of that claim do not require that there is necessarily a vertical flow immunoassay present, therefore, in the absence of a VFI, there is no antecedent basis for the vertical flow immunoassay of claim 10. As the limitations of Claim 10 concern the vertical flow immunoassay, which is not required for Claim 9, the limitations of the claim are satisfied without the application of additional art, as the claimed invention does not require the vertical flow immunoassay.
Regarding Claim 14, Skakoon in view of Mayer discloses as described above, The method of claim 13. For the remainder of Claim 14, Skakoon does not specifically disclose detecting for the presence of a biological interaction between the biomarker detection membrane and the biomarker of the biological specimen.
Koczula teaches detecting for the presence of a biological interaction between the biomarker detection membrane ([Page 112, Paragraph 1] “The sample, together with the conjugated antibody bound to the target analyte, migrates along the strip into the detection zone…a porous membrane (usually composed of nitrocellulose) with specific biological components (mostly antibodies or antigens) immobilized in lines.”) and the biomarker of the biological specimen {Fig 1, [Page 112, Paragraph 1] including “…react with the analyte bound to the conjugated antibody”;[Page 111, Paragraph 3] “… ”lateral flow immunoassays’ (LFIAs), in which antibodies…used as recognition elements”; [Page 111, Paragraph 1] “A variety of biological sample can be tested using LFAs, including…saliva…”)).
The motivation for Claim 14 to combine Skakoon in view of Mayer with Koczula is the same as that described in more detail in Claim 7. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the broadly-described “lateral flow immunoassay test strips” disclosed by Skakoon with Koczula’s taught lateral flow immunoassay test strips with biomarker detectors such as antibodies, creating a single saliva testing device that used immunoassay test strips with antibody biomarker detector regions to detect antigens in saliva.
Regarding Claim 15, Skakoon in view of Mayer discloses as described above, The method of claim 14. For the remainder of Claim 15, Skakoon does not specifically disclose further comprising the step of determining a presence or an absence of the biological specimen from the user who provided the biofluid by introducing the biofluid to the biomarker detection membrane. However, Skakoon broadly discloses at [0087] “Test methodology and reading of results is performed in accordance with normal practice for lateral flow immunoassay test strip use. “ Per the broad definition of immunoassay provided by Merriam-Webster, “a technique or test used to detect the presence or quantity of a substance (such as a protein) based on its capacity to act as an antigen”, the step of determining a presence of the biological specimen from the user who provided the biofluid by introducing the biofluid to the biomarker detection membrane is performed by a “lateral flow immunoassay test strip”.
Koczula teaches the step of determining a presence or an absence of the biological specimen from the user who provided the biofluid Fig 1, [Page 112, Paragraph 1] including “…react with the analyte bound to the conjugated antibody”;[Page 111, Paragraph 3] “… ”lateral flow immunoassays’ (LFIAs), in which antibodies…used as recognition elements”; [Page 111, Paragraph 1] “A variety of biological sample can be tested using LFAs, including…saliva…”; Fig 3 pregnancy test positive or negative)(Examiner notes that an immunoassay “reacts with the analyte bound to the conjugated antibody”, and it would show an absence of biological specimen in its dry, non-reacted state.) by introducing the biofluid to the biomarker detection membrane ([Page 112, Paragraph 1] “The sample, together with the conjugated antibody bound to the target analyte, migrates along the strip into the detection zone…a porous membrane (usually composed of nitrocellulose) with specific biological components (mostly antibodies or antigens) immobilized in lines.”; [Page 111, Paragraph 1] “A variety of biological sample can be tested using LFAs, including…saliva…”)(
The motivation for Claim 15 to combine Skakoon in view of Mayer with Koczula is the same as that described in more detail in Claim 7. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the broadly-described “lateral flow immunoassay test strips” disclosed by Skakoon with Koczula’s taught lateral flow immunoassay test strips with biomarker detectors such as antibodies, creating a single saliva testing device that used immunoassay test strips with antibody biomarker detector regions to detect the presence (or absence) of antigens in saliva from a subject.
Regarding Claim 17, Skakoon in view of Mayer discloses as described above, The method of claim 13. For the remainder of Claim 17, Skakoon discloses further comprising the steps of removing the cap from the collection tube ((Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Fig 7A, Fig 8; [0086] “seal cap 720 can be removed…”);
connecting the cap (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Fig 7A, Fig 8) with the biomarker detection membrane (Figure A: Examiner-annotated “cap”: “seal cap 720” + “housing 802”; Fig 8, [0086] – [0087] “a housing 802, which includes a plurality of lateral flow immunoassay test strips 804 internal to test housing 802”) to the collection tube (Figure 7, Figure 8, “seal cap 720” attached to “collection vessel 702”; [0086] “seal cap 720, which allows access to the collected saliva in collection vessel 702”; Figure 8, “housing 802” attached to “collection vessel 702”; [0087] “inserted into housing 802”)
inverting the collection tube to flow the mixed biofluid and biological reagent through the biomarker detection membrane under gravity ([0084] “…attached collection vessel 102, is then inverted. Inversion allows the saliva held by collection vessel 102 to flow by gravity to make contact with test strips 606.”)(Examiner notes that the tube is inverted with the collection vessel, and the biofluid saliva sample is mixed with the reagent on the immunoassay test strips when the saliva contacts the strips.) or fluid impulse by shaking; and
detecting a presence or an absence of the biomarker in the biofluid by detecting a physio-chemical property perturbation (Fig 8, [0087] “lateral flow immunoassay strip”) such as by a color change (Fig 8; [0087] “Test methodology and reading of results is performed in accordance with normal practice or lateral flow immunoassay strip use”)(Examiner notes the 112(b) interpretation above.) via at least one of
Skakoon does not specifically disclose that the immunoassay test strips work by “color change”. Koczula teaches detecting a presence or an absence of the biomarker in the biofluid ([Page 113] Figure 3, detecting analyte in urine for pregnancy, “positive”, “negative”) by detecting a physio-chemical property perturbation via at least one of a color change ([Page 113] Figure 3, strip area from white to colored line(s) to show results; [Page 115, “Detection methods” Section] “…sensitivity of assays… the antibody–antigen conjugate and by the colorimetric read-out”) and an electrochemical change by an electrochemical reaction that activates or releases a volatile compound in or from the biomarker detection membrane.
Skakoon provides a motivation to combine at [0087] with “Test methodology and reading of results is performed in accordance with normal practice for lateral flow immunoassay test strip use. “ A person having ordinary skill in the art would recognize that a generic “lateral flow immunoassay test strip” as disclosed in Skakoon and depicted in Fig 8 in use would work by a “color change” such that a line appears on a formerly-colorless strip (the lines shown on the white background of the strip in Figure 8). This is how Koczula teaches that the lateral flow immunoassays work.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the broadly-described “lateral flow immunoassay test strips” disclosed by Skakoon with the lateral flow immunoassay test strips that work by color change line indications taught by Koczula, creating a single saliva testing device that shows results with color change indication on immunoassay test strips.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Skakoon in view of Mayer further in view of Skakoon et. al., (US 2013/0092690 A1), hereinafter Skakoon 2013.
Regarding Claim 11, Skakoon in view of Mayer discloses as described above, The device of claim 1. For the remainder of Claim 11,
Skakoon does not disclose an insert body shaped for insertion into a reservoir of the collection tube; a flange on the insert body configured to be supported by an entrance wall of the collection tube a bottom surface having a central opening; and wherein the piercing end corresponds to a spike extending from the bottom surface.
Skakoon 2013 teaches a tube assembly biological specimen container with a piercer movably disposed in the tube to pierce a membrane to facilitate the mixing interaction of a biological specimen with a reagent. Specifically for Claim 11, Skakoon 2013 teaches an insert body shaped for insertion ([0034] “…pierce and guide sealing membrane 207”) into a reservoir of the collection tube (Figures 1, 2, and 7; [0034] “Actuating member 209 configured as a piercer movably assembles onto the vessel wall 209 portion of ampoule cap housing 201 via guide walls 307”)
a flange on the insert body ([0034] “seal lip 309…”) configured to be supported by an entrance wall of the collection tube ([0034] “…which sealingly rides along seal surface 211, which is a portion of the outer side of vessel walls 301”);
a bottom surface having a central opening (Figure 9, an opening within the center of the rounded “shearing edge 901” feature); and
wherein the piercing end corresponds to a spike extending from the bottom surface (Fig 9, “piercing tip 313”)
Skakoon 2013 provides a motivation to combine at [0036] with “its piercing tip 313 has punctured sealing membrane 207 and created a flap 501 out of a portion of sealing membrane 207.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that a sharp, pointed member performing a puncture action could achieve a clean break through the membrane by creating a flap, likely reducing the effort required to make the puncture.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine Skakoon in view of Mayer’s disclosed saliva mouthpiece and tube assembly with a piercing swab (that punctures a membrane to form a liquid connection between saliva samples and flow immunoassay test cards) with Skakoon 2013’s piercing end shaped like a spike (that punctures membrane to form a liquid connection between saliva samples and a reagent), creating a single all-in-one saliva sampling tube-shaped device that can pierce a membrane with a pointed member while it is inserted into the test card housing to let saliva flow onto a test card, minimizing possibilities of lost sample through leakage.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Skakoon in view of Mayer, further in view of Skakoon 2013, further in view of Fountain, et. al., (United States Patent US 5,396,986), hereinafter Fountain.
Regarding Claim 12, Skakoon in view of Mayer, further in view of Skakoon 2013 discloses as described above, The device of claim 11. For the remainder of Claim 12, Skakoon does not disclose wherein the piercing end corresponds to a plurality of physically separated spikes.
Fountain teaches a tube-shaped mixing capsule in which the materials are kept separated in chambers and brought together at the time they are to be mixed, with a two-spiked member that can be depressed and puncture a membrane in the tube, allowing for the liquid in the first chamber to mix with the second chamber. Specifically for Claim 12, Fountain teaches wherein the piercing end corresponds to a plurality of physically separated spikes (Figs 4 and 5, [Col 2, Lines 40 – 43] “Cutting means 19 is any projection capable of piercing partition 37. It is preferably two projections…)
Skakoon in view of Mayer, further in view of Skakoon 2013 teaches a spiked tip on a rounded plastic profile to puncture a membrane to allow material within a tube to flow and mix into another chamber, which is the same function as Fountain’s spiked tips on the rounded plastic profile to puncture a membrane to allow material flow and mixing. Fountain provides a motivation to combine at [Col 2, lines 40 – 42] “Cutting means 19 is any projection capable of piercing partition 37. IT is preferably two projections…” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that two spiked projections is an optional design choice to effectively perform the function of piercing a membrane in a tube when depressed into it.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the single plastic spiked tip on a rounded plastic profile (to puncture a membrane) disclosed in Skakoon in view of Mayer, further in view of Skakoon 2013 for Fountain’s taught multiple spiked tips on a rounded plastic profile (to puncture a membrane), creating a single all-in-one saliva sampling tube-shaped device that can pierce a membrane with multiple spikes while it is inserted into the test card housing to let saliva flow smoothly into a test card chamber.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Skakoon in view of Mayer, further in view of Koczula, further in view of O’Farrell, “Multiplex Assays Part 2: The Power of Spot Arrays in Multiplex Assays”.
Regarding Claim 18, Skakoon in view of Mayer, further in view of Koczula discloses as described above, The method of claim 17. For the remainder of Claim 18, Skakoon does not disclose wherein the biomarker detection membrane comprises an array of detection spots, or an array of detection spots including an array for multiplex detection of a plurality of unique biomarkers, and a positive control.
O’Farrell teaches wherein the biomarker detection membrane ([Page 1] Figure, lateral flow immunoassays shown; [Page 2, 2nd – 3rd Paragraph] “multiplexed LFIs”, “flow rate through an analytical membrane, typically nitrocellulose…”); comprises an array of detection spots ([Page 2, 1st Paragraph] “spot arrays in lateral flow fields”), or an array of detection spots including an array for multiplex detection of a plurality of unique biomarkers ([Page 3, 1st Full paragraph] “One of the most powerful potential applications of the SymbolicsTM lateral flow arraying process is the generation of multiplexed arrays for different analytes on a single strip”), and a positive control ([Page 1] Figure, “CTRL” line; [Page 2, 3rd Paragraph] “…migration through the device to the test and control lines.”)
O’Farrell provides a motivation to combine at [Page 3, 1st Full paragraph] with “One of the most powerful potential applications of the SymbolicsTM lateral flow arraying process is the generation of multiplexed arrays for different analytes on a single strip.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that the array coating on the lateral flow immunoassay could be used to show the presence of multiple analytes using symbols, which would be useful for determining results for multiple analytes in the same test, increasing test result speed for subjects. It would have been predictable to use the spot arrays deposited for multiplex detection of analytes taught by O’Farrell on any similar lateral flow immunoassay test strip, as it would continue to operate with the function of detecting analytes using a lateral flow immunoassay test strip.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the “lateral flow immunoassay test cards” disclosed in Skakoon with the with the spot arrays deposited on lateral flow immunoassay test sheets for multiplex detection of analytes taught by O’Farrell, creating a single saliva testing device that shows results with numeric-shaped color change indication for multiple analytes on a single immunoassay test strip to increase the efficiency of testing for subjects.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Skakoon in view of Meyer, further in view of Carrio et. al., “Automated Low-Cost Smartphone-Based Lateral Flow Saliva Test Reader for Drugs-of-Abuse Detection”, hereinafter Carrio.
Regarding Claim 20, Skakoon in view of Mayer, further in view of Koczula discloses as described above, The method of claim 17. For the remainder of Claim 20,
Skakoon does not disclose further comprising detecting the color change by a digital imaging capture device of a smartphone, and analyzing the detected color change from an image captured by the digital imaging capture device with a data analysis algorithm software to quantify a color change parameter, including at least one of intensity, color wavelength, and distribution thereof.
Carrio teaches a smartphone-based lateral flow immunoassay reader for detecting color and intensity changes at detection zones associated with the colorimetric tests. Specifically for Claim 20, Nelis teaches further comprising detecting the color change by a digital image capture device of a smartphone ([Page 29571, 2nd Full Paragraph] “we present a novel algorithm to qualitatively analyze lateral flow tests using computer vision and machine learning techniques running on a smartphone device.”; [Page 29576, 1st Full Paragraph] “The positions of the camera (a mobile device in our case)”; [Page 29576, Bottom] “…capturing and processing the test images…Apple iPhone 4, 4S and 5.”), and analyzing the detected color change from an image captured by the digital imaging device with a data analysis algorithm software ([Page 29576, Top] “the computer vision algorithms used in the image processing stage are described. Finally, the machine learning algorithms used for lateral histogram classification are presented”; [Page 29591; “Conclusion” Section] “…results…those obtained by the test reader app…”; [Page 29576, Bottom] “…capturing and processing the test images…”) to quantify a color change parameter, including at least one of intensity ([Page 29575, “Interpretation of Results” Section, Paragraph 6] “The intensity of the colored line in the test region…concentration of the analyte present in the specimen.”), color wavelength (Figure 2, Red lines and Blue patch)(Examiner notes that the wavelength is a color), and distribution thereof ([Page 29575, “3.2. Interpretation of Results” Section, Paragraphs 3 - 5] “Negative: Two colored lines appear on the membrane.”, “Positive: Only one colored line appears in the control region”, “Invalid result: No control line is formed”)
Carrio provides a motivation to combine at [Page 29571, Top] with “By using a computer vision algorithm, the user-specific bias is eliminated (ability to interpret), which may affect the result obtained” and [Page 29573, Paragraph 4] “The proposed image processing methodology can be applied to any line presence or absence-based or color interpretation-based immunoassay tests on the market.” A person having ordinary skill in the art before the effective filing data of the claimed invention would recognize that using a smartphone method of determining color change on an immunoassay test strip would improve a person’s ease in determining the color-associated results on an immunoassay test card.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the saliva test device with flow immunoassay disclosed in the Skakoon with the smartphone-implemented immunoassay test reader, creating a single saliva testing device that interprets its immunoassay results using a smartphone application.
Response to Arguments
Applicant's arguments filed 20 March 2026 have been fully considered but they are not persuasive.
Regarding the 35 U.S.C. 102 and 103 Rejections:
Applicant argues at [Page 12, Bottom] – [Page 13, Top] that Mayer does not teach a “piercing element” within the meaning of claim 1. Looking to the 35 U.S.C. 103 rejection above, Mayer teaches the “tip of the swab 210” of Figure 2A – C such that [0069] “cause the tip of the swab 210 to puncture the solution chamber 206”. The swab tip is a piercing element that pierces, or “punctures” the solution chamber. The argument is not persuasive.
Applicant argues at [Page 13, 1st Full Paragraph] that the element of “a biomarker detection membrane configured to connect to the cap after the reservoir membrane is removed to detect one or more biomarkers in the biofluid” is not disclosed, taught, or suggested by the cited references because Skakoon’s disclosed test strips are neither a membrane, nor part of a cap or a test for biomarkers.
As described above, Skakoon discloses a [0087] “plurality of lateral flow immunoassay test strips” and [0087] “Test methodology and reading of results is performed in accordance with normal practice for lateral flow immunoassay strip use.” As evidenced by Koczula, “Lateral flow assays,” [Page 112, Paragraph 1 ], “A typical lateral flow test strip…consists of overlapping membranes that are mounted on a backing card for better stability and handling”. Also evidence by Koczula, “Lateral flow assays,” [Page 111, Introduction, Paragraph 1], “The lateral flow assay (LFA) is a paper-based platform for the detection and quantification of analytes in complex mixtures”, and [Page 117, “Conclusion section”] with “The unique and remarkable properties of LFAs have contributed to the detection of disease biomarkers…the principle of the method has remained unchanged for decades”. Based on Skakoon’s disclosure of a lateral flow immunoassay test strip using in accordance with normal practice, Skakoon discloses a membrane as part of the test strip, which is used as a test for biomarkers.
Regarding the test strips as part of a cap, looking to the 35 U.S.C. analysis above and Examiner-annotated Figure A: Examiner-annotated Skakoon Figure 8 of “cap”: Skakoon discloses a collective cap including “seal cap 720” + “housing 802” that can attach as a collective cap unit to the “collection vessel 702” tube. The “housing 802” portion includes a place that stores the lateral flow assay strips, such that the lateral flow assay strips are part of the cap.
The argument is not persuasive.
Applicant summarily argues at [Page 13, 2nd Full Paragraph] that the remainder of the claims are dependent upon the independent claims, and are patentable over the cited prior art for at least the same aforementioned reasons. Based on the 35 U.S.C 103 analysis herein and the discussion of arguments above, the dependent claims are not patent-eligible under 35 U.S.C. 103. The argument is not persuasive.
Applicant argues at [Page 13, 3rd Full Paragraph] that regarding claims 5, 23, and 25, none of the cited references are understood to teach a reservoir membrane that is removed after the biological reagent is introduced to the biofluid in a collection tube. Looking to the 35 U.S.C. 103 rejection above, as claimed relative to the “devices”, the removal of the reservoir membrane is functionally claimed such that the apparatus must be configured to allow for the removal of the reservoir membrane after the biological reagent is introduced to the biofluid. Skakoon discloses an assembly including a peelable or puncturable sealed-foil covering [0086]. As discussed above, a sealed-foil covering that is both puncturable and peelable is configured such that it can functionally be peeled off after it has been punctured. Puncturing the membrane is sufficient to allow the sample to flow and contact the test strips with the saliva collection device inserted into housing 802. The sealed-foil covering is also configured such that the peelable foil covering could be peeled-off and removed after it has been punctured, by removing the saliva collection device from the housing and peeling the foil covering after the sample saliva fluid has contacted the test strip (and the biological reagent thereon). The argument is not persuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MELISSA J MONTGOMERY whose telephone number is (571)272-2305. The examiner can normally be reached Monday - Friday 7:30 - 5:00 ET.
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/MELISSA JO MONTGOMERY/Examiner, Art Unit 3791
/PATRICK FERNANDES/Primary Examiner, Art Unit 3791
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