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 .
Claims 1-68 are the currently pending claims hereby under examination.
Claim Objections
Claims 16-19, 20-24, 27, 64-65, and 67 are objected to because of the following informalities:
In claim 16, line 1: "the storage container”, lacks proper antecedent basis and should read "the at least one storage container”;
In claims 17 (lines 1-2), 18 (line 2), 19 (lines 1), 21 (lines 1-2 and 2), 22 (lines 2 and 3), 23 (line 2), and 24 (lines 1-2): "said stimulating and collecting material” lacks proper antecedent basis and should read "said at least one stimulating and collecting material”;
In claim 20, lines 1-2: "the storage container”, lacks proper antecedent basis and should read "the at least one storage container”;
In claim 21, line 1, “The device of claim 21” appears to be a typographical error that should read “The device of claim 20”;
In claim 21, line 1: “said preservative” lacks proper antecedent basis and should read "said at least one preservative”;
In claim 21, line 3: “said storage container” lacks proper antecedent basis and should read "said at least one storage container”;
In claim 27, line 1: “A method of collection a sweat sample” is grammatically incorrect and should be “A method of collecting a sweat sample”;
In claim 64, line 2: "the stimulating and collecting material” lacks proper antecedent basis and should read" the at least one sweat stimulating and collecting material”;
In claim 65, line 1: "the stimulating and collecting material” lacks proper antecedent basis and should read" the at least one sweat stimulating and collecting material”;
In claim 67, line 1: “said preservative” lacks proper antecedent basis and should read "said at least one preservative”; and
In claim 67, lines 1-2: "the stimulating and collecting material” lacks proper antecedent basis and should read" the at least one sweat stimulating and collecting material”.
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 14, 17-18, 30, 34, 51-52, and 61-63 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claim 14 recites "the at least one sweat stimulating and collecting iontophoresis material” in lines 1-2, but there is a lack of antecedent basis for this limitation in the claim. The Examiner is interpreting this to read "the at least one sweat stimulating and collecting material".
Claim 17 recites “The device of claim 15” in line 1 and "said desiccant” in line 1, but there is a lack of antecedent basis for this limitation in the claim. The Examiner is interpreting this to read "said at least one desiccant" and depend on claim 16 in order to maintain proper antecedent basis.
Claim 18 recites “the device of claim 1 and "said storage container” in line 1, but there is lack of proper antecedent basis for this limitation in the claim. The Examiner is interpreting this to read as “said at least one storage container” and claim 18 to depend on claim 15 in order to maintain proper antecedent basis.
Claim 30 recites "at least one sweat-stimulating component” in line 1, but there is a lack of antecedent basis for this limitation in the claim. The Examiner is interpreting this to read as "at least one sweat-stimulating substance” as shown in claim 29 lines 2-3.
Claim 34 recites "said stimulating and collecting material” in lines 2-3, 3, and 5, but there is a lack of antecedent basis for this limitation in the claim. The Examiner is interpreting this to read as "said material”.
Claims 51 and 52 are rejected by virtue of their dependence from claim 34.
Claim 61 refers to "at least one sweat stimulating and collecting iontophoresis material” in lines 2-3, but there is a lack of antecedent basis for this limitation in the claim. The Examiner is interpreting this to read as "at least one sweat stimulating and collecting material”.
Claims 62 and 63 are rejected by virtue of their dependence from claim 61.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-7, 11-14, 23, 25-26, 29-32, 53, 58, and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Peyser et al. (US-20070027383-A1), hereto referred as Peyser, and further in view of Sembrowich et al. (US-5036861-A), hereto referred as Sembrowich, and further in view of Heikenfeld et al. (WO-2018005438-A1), hereto referred as Heikenfeld.
Regarding claim 1, Peyser partially teaches that a sweat collecting device comprising at least one sweat stimulating and collecting material. Specifically, Peyser teaches a sweat collection device comprising a microfluidic collection layer with a sweat-inducing mechanism (Peyser, ¶[0067]), but does not expressly disclose that the microfluidic collection layer or channel itself is made of or contains an absorbent material, as required by the explicit definition in the present specification ([0018]). Sembrowich teaches a patch device that includes a sweat-inducing agent and collects sweat in the same material. (Sembrowich, col. 1, ll. 22–40: "Medical iontophoresis is employed to pharmacologically stimulate a sweating response using a test patch containing a sweat-inducing agent. The test patch collects the sweat and is then used to provide sweat for analysis...") and (col. 2, ll. 38–54: "Applying a direct current to skin patch 20 causes the pharmacologic solution to be transdermally introduced... Once introduced, the pharmacologic solution stimulates sweat... Once the sweat reaches the skin surface, skin patch 20 is removed and the sweat is collected..."). This demonstrates the use of a single material or pad that both stimulates sweat and collects it, satisfying the functional integration required by the claim. While Sembrowich satisfies the functional requirement of a single material for sweat stimulation and collection, Heikenfeld supports the understanding that sweat collection systems may employ either absorbent materials or microfluidic channels as a matter of design choice, with both approaches being functionally interchangeable. Heikenfeld teaches that sweat collectors may include absorbent gels, textiles, cavities, or microfluidic channels capable of transporting sweat away from the skin (Heikenfeld, ¶[0014]). Heikenfeld further explains that different types of collectors may be selected or combined based on their absorptive and transport properties to meet performance objectives (Heikenfeld, ¶[0012], [0014]). This establishes that the selection between a material-based system (e.g., absorbent gel) and a channel-based system (e.g., Peyser's microfluidics) was known in the art and considered functionally equivalent in achieving reliable sweat collection. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Peyser in view of Sembrowich and Heikenfeld to provide a collection layer comprising or containing an absorbent material (such as a gel, pad, or absorbent channel) capable of absorbing the sweat it stimulates, as required by the specification’s definition. The combination would have been feasible because Peyser provides the device framework, Sembrowich demonstrates the integration of stimulation and collection in a single pad, and Heikenfeld supports interpreting channels as absorbent materials. The benefit of this combination would be to improve sweat sample integrity and reliability by maximizing sample absorption, minimizing analyte loss, and simplifying device design.
Regarding claim 2, the combined Peyser, Sembrowich, and Heikenfeld teaches that the at least one sweat stimulating and collecting material includes a sweat stimulant (Peyser, ¶[0067]: “administering sweat inducing agents such as pilocarpine with or without a penetration enhancer or iontophoresis”, this shows the sweat stimulating and collecting material includes the sweat stimulant pilocarpine).
Regarding claim 3, the combined Peyser, Sembrowich, and Heikenfeld teaches that the sweat stimulant includes at least one of pilocarpine, methacholine, or carbachol (Peyser, ¶[0067]: “sweat inducing agents such as pilocarpine with or without a penetration enhancer or iontophoresis”, this shows pilocarpine is included as a sweat stimulant).
Regarding claim 4, the combined Peyser, Sembrowich, and Heikenfeld teaches that the device comprises at least one sweat stimulating and collecting material, but does not disclose that the material further includes at least one preservative. Rather, the combined Peyser, Sembrowich, and Heikenfeld teaches a device comprising at least one sweat stimulating and collecting material (Peyser, ¶[0067]) for the purpose of measuring analytes such as glucose collected in the patch (Peyser, ¶[0043]). However, Peyser does not disclose that the sweat stimulating and collecting material further includes at least one preservative. Sembrowich teaches that a material for stimulating sweat may further include a preservative to maintain and preserve an analyte such as glucose in the collected sweat. Sembrowich states that the sweat can be “pharmacologically modified to contain the constituent (e.g. glucose)” (Sembrowich, col. 1, lines 55-65), and further explains, “Once introduced, the pharmacologic solution stimulates sweat in the eccrine sweat gland and preserves glucose levels in the secretion as the secretion moves to the skin surface through the lumen of the gland” (Sembrowich, col. 2, lines 48-54). Sembrowich also describes that when iontophoresis is used, the gel contains agents which, “when transdermally introduced, modify the sweat gland secretion mechanism so that the secretion appearing at the surface of the skin contains glucose which is preserved in the sweat at levels in equilibrium with (or in a known relationship to) those found in plasma. ... An example of such a compound is glucose-6-phosphate… the glucose transport inhibitor used in gel 34 is phlorizin” (Sembrowich, col. 3, lines 1-27). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Sembrowich to include at least one preservative in the sweat stimulating and collecting material. The combination would be possible because Sembrowich teaches inclusion of preservatives compatible with the device and methods of Peyser, and it would be obvious to apply this to maintain analyte stability during sweat collection, as both arts analyze glucose. The benefit of this combination would be to enable more accurate measurement of analytes such as glucose by preserving their concentration during transport and collection.
Regarding claim 5, the combined Peyser, Sembrowich, and Heikenfeld does not teach that the at least one preservative is non-ionic and skin safe. Rather, the combined Peyser, Sembrowich, and Heikenfeld establish a device comprising at least one sweat stimulating and collecting material that includes a preservative for maintaining analyte stability during collection and storage, as shown above in claim 4, but it does not expressly disclose that the preservative is non-ionic and skin safe. Peyser, however, teaches the use of alcohols (such as ethanol and other higher alcohols) as penetration enhancers in the sweat stimulating and collecting material (Peyser, ¶[0057]). Alcohols are well known in the art to possess antimicrobial properties and are routinely used as preservatives in pharmaceutical and cosmetic formulations. They are also non-ionic and widely recognized as skin safe at the concentrations employed for topical application. It would have been prima facie obvious before the effective filing date of the claimed invention to modify the combined Peyser, Sembrowich, and Heikenfeld in view of Peyser by using alcohol as the preservative, since alcohol is already present in the Peyser device for direct skin contact and is known to be both non-ionic and skin safe. The motivation to do so would be to reduce the number of different chemicals in the formulation, simplify manufacturing, and ensure compatibility with iontophoresis, while maintaining analyte stability. The feasibility of this combination is clear, as alcohol is already present in the device in direct skin contact, and its use as a preservative would require no substantive modification. The benefit of this combination would be a sweat collection device that effectively preserves analytes, is simple and cost-effective to manufacture, and ensures user safety during skin contact.
Regarding claim 6, the combined Peyser, Sembrowich, and Heikenfeld teaches that the device further comprises an iontophoresis electrode associated with the at least one sweat stimulating and collecting material (Peyser, ¶[0067]: "chemically (e.g., by administering sweat inducing agents such as pilocarpine with or without a penetration enhancer or iontophoresis)", this teaches the use of iontophoresis for administering a sweat stimulant, indicating an iontophoresis electrode is part of the device; ¶[0057]: "Pilocarpine may also be driven into the skin using iontophoresis. The present inventors have shown that the infusion of pilocarpine into the skin using iontophoresis increases the amount of sweat by about 20 fold per unit area", this shows that the patch/device uses iontophoresis to administer the sweat stimulant, which necessarily requires an iontophoresis electrode associated with the sweat stimulating and collecting material; ¶[0086]: "the detector typically comprises at least two electrodes, which are typically activated by the measurement device when it is brought into electrical contact with the patch", this shows the patch/device includes at least two electrodes for activation; ¶[0087]: "the interface layer comprises at least one electrode, which is activated by the measurement device when placed into electrical contact with the patch", this explains that an electrode is present in the device and can be activated for measurement or stimulation; ¶[0139]: "Cotton pads soaked in a buffered saline and 1% pilocarpine solution were applied respectively to the negative and positive electrodes of a standard iontophoresis device A charge (dose) of 10 mA-min at a current of 1 mA was applied to the electrodes as they were held tightly against the skin of the subjects with elastic straps", this directly shows the use of positive and negative electrodes in an iontophoresis device for sweat stimulation, which aligns with the claim requirement for an iontophoresis electrode associated with the sweat stimulating and collecting material).
Regarding claim 7, the combined Peyser, Sembrowich, and Heikenfeld does not fully teach that the device further comprises a second iontophoresis electrode associated with a sweat stimulating material. Rather, Peyser teaches that “Cotton pads soaked in a buffered saline and 1% pilocarpine solution were applied respectively to the negative and positive electrodes of a standard iontophoresis device,” indicating the use of two separate electrodes in contact with sweat stimulating material (pilocarpine), which corresponds to the claimed first and second iontophoresis electrodes (Peyser, ¶[0139]). However, while these pads are associated with the stimulating and collecting material, they are not the material itself. Sembrowich explicitly discloses a skin patch having two separate pads each containing a pharmacologic stimulating solution and each associated with an iontophoresis electrode. Specifically, Sembrowich (col. 2, ll. 38–54) states: “Applying a direct current to skin patch 20 causes the pharmacologic solution to be transdermally introduced... Once introduced, the pharmacologic solution stimulates sweat in the eccrine sweat gland...” and FIG. 2 describes “patches 30 and 32 containing pharmacologic solutions and electrodes 26 and 28” where the electrodes are connected and function through the collecting pads (Sembrowich, col. 2, ll. 55-64). This structure teaches a first and second sweat stimulating pad each associated with its own electrode for iontophoresis. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined Peyser, Sembrowich, and Heikenfeld view of Sembrowich to provide a sweat stimulation and collection system comprising two sweat stimulating pads each associated with a respective iontophoresis electrode, as taught in Sembrowich. The combination would have been feasible because both references teach the use of multiple electrodes and sweat stimulating materials in iontophoresis patches, and it would have been obvious to use such a configuration to ensure uniform delivery and stimulation across the skin. The benefit of this combination would be improved control and efficiency of pilocarpine delivery, as well as consistent sweat stimulation and collection using standard iontophoresis techniques.
Regarding claim 11, the combined Peyser, Sembrowich, and Heikenfeld teaches that the device further comprises at least one pressure-providing material associated with the at least one sweat stimulating and collecting material (Peyser, ¶[0055]: "The patch may also comprise an adhesive or an adhesive layer, for example, to help adhere the patch to the skin surface The adhesive material may comprise an annular overlay layer or it may comprise a layer of adhesive contemporaneous and coextensive with at least one other patch layer Any suitable adhesive may be used For example, common pressure sensitive adhesives known in the transdermal patch arts, such as silicone, polyacrylates, and the like, may be used", this teaches that a pressure-providing adhesive layer is associated with the sweat stimulating and collecting material, ensuring close contact with the skin; ¶[0060]: "the measurement device... is brought into contact with the patch and force is applied to the patch in a manner sufficient to cause an increase in the transport of sweat to the skin The applied pressure over the collection patch results in fluid from the sweat gland lumen being expressed and delivered to the skin surface", this teaches that the device may include a component or mechanism for applying pressure to the patch, thereby functioning as a pressure-providing material to promote coupling of the sweat stimulating and collecting material to the skin).
Regarding claim 12, the combined Peyser, Sembrowich, and Heikenfeld does not teach that the device further comprises at least one wicking material associated with at least one sweat stimulating and collecting material. Rather, the combined Peyser, Sembrowich, and Heikenfeld teaches a patch comprising a microfluidic collection layer and a sweat stimulating mechanism, and describes that the microfluidic collection layer may collect sweat by capillary or “wicking” action (Peyser, ¶[0015]; ¶[0067]). Peyser further teaches that the patch may include a waste reservoir for sweat collection (Peyser, ¶[0063]). However, Peyser does not disclose at least one distinct wicking material associated with at least one sweat stimulating and collecting material. Heikenfeld teaches that a device for collecting sweat may include a wicking waste reservoir (138) associated with waste collectors and a stimulant gel (sweat stimulating material), where the wicking component assists in collecting excess sweat and transporting it away from the skin (Heikenfeld, ¶[0012]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Heikenfeld to include at least one wicking material associated with at least one sweat stimulating and collecting material. One of ordinary skill in the art would have recognized that integrating a wicking material with the sweat stimulating and collecting material, as described in Heikenfeld, would improve sweat collection efficiency and prevent pooling or backflow within the patch. The benefit of this combination would be enhanced and more reliable sweat transport into the waste reservoir, resulting in more efficient and functional sweat collection for analysis.
Regarding claim 13, the combined Peyser, Sembrowich, and Heikenfeld does not teach that the at least one wicking material has a capillary pressure less than a capillary pressure of the at least one sweat stimulating and collecting material. Rather, the combined Peyser, Sembrowich, and Heikenfeld teach an additional wicking material as shown above in claim 12. However, it does not disclose a wicking material having a capillary pressure less than the capillary pressure of the sweat stimulating and collecting material. Heikenfeld teaches that the wicking waste reservoir (138) is designed to have a capillary pressure less than that of the stimulant gel (140), such that fluid is collected into the waste reservoir without drawing fluid out of the stimulant gel (Heikenfeld, ¶[0012]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Heikenfeld in order to have a wicking material that has a capillary pressure less than a capillary pressure of the sweat stimulating and collecting material. The combination would have been feasible because the combined Peyser and Heikenfeld describe sweat collection devices that utilize reservoirs, stimulant gels, and wicking components for fluid management, and Heikenfeld provides explicit guidance on controlling capillary pressure between associated materials. One of ordinary skill in the art would have recognized that adapting the capillary pressures as taught by Heikenfeld would prevent fluid loss from the stimulant gel while enabling efficient sweat transport to the waste reservoir. The benefit of this combination would be improved reliability and selectivity of sweat collection, minimizing interference with the stimulant gel while promoting efficient transport of sweat to the waste reservoir.
Regarding claim 14, the combined Peyser, Sembrowich, and Heikenfeld does not disclose that the at least one sweat stimulating and collecting iontophoresis material has a degree of hydration such that the volume of the at least one sweat stimulating and collecting material is at least one of 1%, 5%, 10%, 20%, 50%, 90% or less than the volume of the at least one sweat stimulating and collecting material in a fully hydrated state. Rather, the combined Peyser, Sembrowich, and Heikenfeld teaches a sweat collection device comprising a sweat stimulating and collecting iontophoresis material (Peyser, ¶[0067]: "the microfluidic collection layer is combined with a sweat-inducing layer, or one or more mechanisms for inducing sweat..."), but does not disclose any specific degree of hydration or a relationship between hydration state and material volume. Heikenfeld teaches that sweat collectors may comprise gels (such as agar) as suitable materials for collecting sweat (Heikenfeld, ¶[0014]). It is well known to those skilled in the art that gels, including agar, swell upon hydration and their volume varies with water content. Therefore, a person of ordinary skill in the art would recognize that gels (including agar) used as sweat collecting materials, as taught by Heikenfeld, are well known to undergo marked volume changes during hydration and drying cycles, readily covering at least a substantial portion of the claimed degrees of hydration, such as 1%, 5%, 10%, 20%, 50%, and 90% of their fully hydrated volume. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Heikenfeld to employ a sweat stimulating and collecting iontophoresis material comprising a hydrogel (such as agar) with a degree of hydration such that its volume changes by at least one of 1%, 5%, 10%, 20%, 50%, or 90% or less than the volume in a fully hydrated state. One of ordinary skill in the art would understand that drying a hydrogel before use predictably increases its subsequent fluid uptake capacity, much like a common sponge. One of ordinary skill in the art would recognize that reducing the initial water content of the hydrogel allows the material to absorb more sweat during use, and would reasonably select an amount of drying (such as 50%) as a matter of routine optimization to maximize sweat uptake based on device needs or diagnostic requirements. The motivation for doing so is clear: increasing the hydrogel’s capacity to collect sweat improves the efficiency of analyte collection and enables more robust diagnostic analysis. The benefit of this combination would be to provide a hydrogel that is capable of absorbing a greater volume of sweat, resulting in improved sample collection, more accurate analysis, and increased flexibility of the device for a range of sweat volumes. The combination would have been feasible because both references describe sweat collection devices using hydrophilic materials, and it would have been obvious to employ a material with a variable hydration state as needed for efficient collection.
Regarding claim 23, the combined Peyser, Sembrowich, and Heikenfeld teaches that the device further comprises an extraction solution to remove collected sweat sample from said stimulating and collecting material, wherein the extraction of sweat sample is at least one greater than 20%, 50%, or 90% of the collected sample (Peyser, ¶[0078]: "a buffer (e.g., phosphate buffered saline, or the like) is used to assist in the collection of sweat For example, the collection layer may include a channel (e.g., microfluidic channel, tubing, etc.) or passage through which the buffer may be perfused", this teaches use of a buffer/extraction solution to collect and remove sweat sample; ¶[0080]: "buffer is moved through the device by allowing a pressurized bolus of buffer to enter the microfluidic channel and push sweat containing glucose from the collection layer into, and ultimately, through the detector layer", this explains the extraction solution (buffer) is introduced under pressure to move the sweat from the collection layer for analysis, and is designed to extract the entire volume of collected sample, thus fully supporting extraction greater than 20%, 50%, or 90% of the collected sample, see also ¶[0078]-[0082]).
Regarding claim 25, the combined Peyser, Sembrowich, and Heikenfeld teaches that the at least one sweat stimulating and collecting material includes a sweat stimulant and a fluid to enhance diffusion of the sweat stimulant into the skin (Peyser, ¶[0057]: "the patch comprises pilocarpine with or without a penetration or permeation enhancer to induce sweat chemically or pharmacologically", this shows the sweat stimulating material includes a sweat stimulant (pilocarpine) and that a penetration enhancer (which may be a fluid) can be used to enhance diffusion; ¶[0057]: "Examples of suitable permeation enhancers include, but are not limited to ethanol and other higher alcohols, N-decylmethylsulfoxide (nDMS), polyethylene glycol monolaurate, propylene glycol monolaurate, dilaurate and related esters, glycerol mono-oleate and related mono, di and trifunctional glycerides, diethyl toluamide, alkyl or aryl carboxylic acid esters of polyethyleneglycol monoalkyl ether, and polyethyleneglycol alkyl carboxymethyl ethers", this further supports that various fluid penetration enhancers can be included to promote the diffusion of the sweat stimulant into the skin).
Regarding claim 26, the combined Peyser, Sembrowich, and Heikenfeld does not teach that the sweat stimulant is carbachol. Rather, the combined Peyser and Heikenfeld teaches a sweat collection device comprising a sweat stimulating and collecting material including a sweat stimulant (see claims 1 and 15 above), but does not disclose that the sweat stimulant is carbachol. Heikenfeld teaches that the stimulant reservoir may include carbachol as a slowly metabolizing chemical stimulant (Heikenfeld, ¶[0013]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the sweat stimulating and collecting material of the combined Peyser, Sembrowich, and Heikenfeld to the sweat stimulant carbachol as taught by Heikenfeld. The combination would have been feasible because both Peyser and Heikenfeld describe sweat stimulation via iontophoresis and the use of chemical stimulants in similar collection device formats, making the substitution of one well-known sweat stimulant for another within the same functional context routine. One of ordinary skill in the art would have recognized that carbachol, identified by Heikenfeld as a slowly metabolizing chemical stimulant suitable for iontophoresis, could be substituted for pilocarpine or other stimulants in Peyser to achieve longer or more sustained sweat collection, as carbachol provides extended stimulation times (Heikenfeld, ¶[0013]). The benefit of this combination would be to provide longer sweat collection times or more sustained stimulation, as explicitly described by Heikenfeld.
Regarding claim 29, the combined Peyser, Sembrowich, and Heikenfeld partially teaches a method of stimulating and collecting sweat, comprises: stimulating the production of sweat in a subject by delivering at least one sweat-stimulating substance out of a material and into contact with the skin of a subject, and collecting at least a portion of the sweat in the material. Specifically, the combined Peyser, Sembrowich, and Heikenfeld teaches a sweat collection device comprising a microfluidic collection layer with a sweat-inducing mechanism (Peyser, ¶[0067]), but does not expressly disclose that the microfluidic collection layer or channel itself is made of or contains an absorbent material, as required by the explicit definition in the present specification ([0018]). Sembrowich teaches a patch device that includes a sweat-inducing agent and collects sweat in the same material. (Sembrowich, col. 1, ll. 22–40: "Medical iontophoresis is employed to pharmacologically stimulate a sweating response using a test patch containing a sweat-inducing agent. The test patch collects the sweat and is then used to provide sweat for analysis...") and (col. 2, ll. 38–54: "Applying a direct current to skin patch 20 causes the pharmacologic solution to be transdermally introduced... Once introduced, the pharmacologic solution stimulates sweat... Once the sweat reaches the skin surface, skin patch 20 is removed and the sweat is collected..."). This demonstrates the use of a single material or pad that both stimulates sweat and collects it, satisfying the functional integration required by the claim. While Sembrowich satisfies the functional requirement of a single material for sweat stimulation and collection, Heikenfeld supports the understanding that sweat collection systems may employ either absorbent materials or microfluidic channels as a matter of design choice, with both approaches being functionally interchangeable. Heikenfeld teaches that sweat collectors may include absorbent gels, textiles, cavities, or microfluidic channels capable of transporting sweat away from the skin (Heikenfeld, ¶[0014]). Heikenfeld further explains that different types of collectors may be selected or combined based on their absorptive and transport properties to meet performance objectives (Heikenfeld, ¶[0012], [0014]). This establishes that the selection between a material-based system (e.g., absorbent gel) and a channel-based system (e.g., Peyser's microfluidics) was known in the art and considered functionally equivalent in achieving reliable sweat collection. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Sembrowich and Heikenfeld to provide a collection layer comprising or containing an absorbent material (such as a gel or wicking textile) capable of absorbing the sweat it stimulates, as required by the specification’s definition, for the advantage of unifying sweat stimulation and collection in a single absorbent structure. The combination would have been feasible because Peyser provides the device framework, Sembrowich demonstrates the integration of stimulation and collection in a single pad, and Heikenfeld supports interpreting channels as absorbent materials. The benefit of this combination would be to improve sweat sample integrity and reliability by maximizing sample absorption, minimizing analyte loss, and simplifying device design.
Regarding claim 30, the combined Peyser, Sembrowich, and Heikenfeld teaches that delivering at least one sweat-stimulating component further comprises use of an electric current to transport said at least one sweat-stimulating substance to the skin (Peyser, ¶[0057]: "Pilocarpine may also be driven into the skin using iontophoresis. The present inventors have shown that the infusion of pilocarpine into the skin using iontophoresis increases the amount of sweat by about 20 fold per unit area", this teaches that the sweat-stimulating substance (pilocarpine) is delivered into the skin using iontophoresis, which is the use of an electric current to transport the substance to the skin; ¶[0067]: "the microfluidic collection layer may include a mechanism for inducing sweat that acts mechanically (e.g., by using an occlusive backing layer, a vacuum, etc.), chemically (e.g., by administering sweat inducing agents such as pilocarpine with or without a penetration enhancer or iontophoresis), or thermally (e.g., by applying a heater, or initiating an exothermic chemical reaction, etc.)", this further supports that the method includes delivery of a sweat-stimulating substance via iontophoresis, which is the use of electric current to drive the substance into the skin).
Regarding claim 31, the combined Peyser, Sembrowich, and Heikenfeld teaches the method of claim 29, further comprising the use of a fluid to enhance diffusion of the sweat-stimulating substance into the skin (Peyser, ¶[0057]: "the patch comprises pilocarpine with or without a penetration or permeation enhancer to induce sweat chemically or pharmacologically. The use of a penetration enhancer may help increase the rate at which the pilocarpine enters the body and thereby, increase the onset of the enhanced sweat response. Examples of suitable permeation enhancers include, but are not limited to ethanol and other higher alcohols, N-decylmethylsulfoxide (nDMS)...", this teaches that a fluid (such as ethanol or other enhancers) is used to enhance diffusion of the sweat-stimulating substance into the skin).
Regarding claim 32, the combined Peyser, Sembrowich, and Heikenfeld teaches that the fluid is included in said material (Peyser, ¶[0067]: "the microfluidic collection layer is combined with a sweat-inducing layer... chemically (e.g., by administering sweat inducing agents such as pilocarpine with or without a penetration enhancer...)", with ¶[0067]: "the mechanism for inducing sweat may be included within the microfluidic channel within the microfluidic collection layer. For example a buffer within the microfluidic channel may include a pilocarpine solution", and with the structure of the collection layer as shown in FIG. 2B and described in ¶[0063], this supports that a penetration enhancer (a fluid) can be included in the sweat-inducing and collecting material (the microfluidic collection layer), showing that the fluid is included in said material; See also Peyser, ¶[0078]-[0080]: "the buffer...is used to assist in the collection of sweat...the collection layer may include a channel...through which the buffer may be perfused", supporting that the buffer containing the enhancer and/or stimulant is physically present in the microfluidic collection layer (i.e., the material), so the fluid is included in said material during operation).
Regarding claim 53, the combined Peyser, Sembrowich, and Heikenfeld does not expressly disclose that stimulating the production of sweat in a subject results in the generation of sweat at a rate of 5 nL/min/gland. Rather, the combined Peyser, Sembrowich, and Heikenfeld, as shown above in claim 29, teaches stimulating and collecting sweat using an absorbent material, but does not disclose or limit the sweat rate to 5 nL/min/gland. However, Heikenfeld, teaches that sweat generation rates can be selected and adjusted based on chemical stimulation, disclosing an example rate of 1 nL/min/gland (Heikenfeld, ¶[0020]), showing that sweat stimulation parameters are controlled to achieve a desired rate. A person of ordinary skill in the art would recognize that higher rates (e.g., 5 nL/min/gland) are achievable by routine adjustment of device settings (such as stimulant concentration or current). Peyser additionally shows that a sweat gland can produce “about 2 nL/min to about 20 nL/min”, showing that the rate of 5 nL/min/gland is well within the expected range (Peyser, ¶[0083]). It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the method of the combined Peyser, Sembrowich, and Heikenfeld and Heikenfeld by routine optimization of stimulation parameters to achieve sweat at a rate of 5 nL/min/gland, as the art teaches such control and selection. The benefit would be improved flexibility and tailoring of sweat collection to specific analytical requirements.
Regarding claim 58, the combined Peyser, Sembrowich, and Heikenfeld does not expressly teach that the material is an iontophoresis material. Peyser teaches that iontophoresis may be used to deliver pilocarpine into the skin to induce sweating (Peyser, ¶[0057]: "Pilocarpine may also be driven into the skin using iontophoresis. The present inventors have shown that the infusion of pilocarpine into the skin using iontophoresis increases the amount of sweat by about 20 fold per unit area"), and mentions that the microfluidic collection layer may include sweat-inducing mechanisms including iontophoresis (Peyser, ¶[0067]). However, Peyser does not describe that the same material or patch used to collect sweat is also used to perform iontophoresis. Sembrowich, in contrast, clearly discloses a sweat patch in which the sweat-inducing function via iontophoresis and the sweat collection function are both performed by the same material. (Sembrowich, FIG. 1-3, col. 1, ll. 22–40: "Medical iontophoresis is employed to pharmacologically stimulate a sweating response using a test patch containing a sweat-inducing agent. The test patch collects the sweat and is then used to provide sweat for analysis...") and (col. 2, ll. 38–54: "Applying a direct current to skin patch 20 causes the pharmacologic solution to be transdermally introduced... Once introduced, the pharmacologic solution stimulates sweat... Once the sweat reaches the skin surface, skin patch 20 is removed and the sweat is collected..."). Additionally, Sembrowich describes the structure of the patch: "patches 30 and 32 containing pharmacologic solutions" and are coupled with electrodes for iontophoretic delivery (Sembrowich, FIG. 2, col. 2, ll. 55–68). This demonstrates that the same patch material that performs iontophoresis also serves to collect the induced sweat. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined Peyser, Sembrowich, and Heikenfeld in view of Sembrowich to ensure that the sweat stimulating and collecting material is itself an iontophoresis material. The combination would have been feasible because Peyser already uses iontophoresis as a sweat-inducing method, and Sembrowich teaches a fully integrated patch design where the same material serves both roles. The benefit of this combination would be simplification of the device architecture and improved efficiency in sweat collection by co-locating sweat induction and collection in the same material.
Regarding claim 68, the combined Peyser, Sembrowich, and Heikenfeld does not teach that the sweat collection device may further comprise at least one analyte sensor. Rather, the combined Peyser, Sembrowich, and Heikenfeld teach a stimulating and collecting material as shown in claim 1 above, but does not explicitly teach an analyte sensor. Peyser teaches several sensor and detection configurations for measuring analytes collected in sweat: “Several types of suitably sensitive detectors may be used... electrochemical-based, or may be fluorescent-based” (Peyser, ¶[0085]-[0087], [0094]). This includes enzymatic glucose sensors that produce a measurable current in proportion to the glucose concentration in sweat. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Peyser to include a sensor or detection chemistry for analyte sensing. The combination would have been feasible because Peyser explicitly teaches the integration of detection mechanisms within the collection patch, and such detection chemistries are suitable for both in situ analysis and post-collection analysis of stored samples. The benefit of this combination would be to enable real-time or near real-time monitoring and quantification of sweat analytes, as well as allowing reliable detection and quantification of analytes from stored samples, thereby improving device functionality and enabling diagnostic or therapeutic decision-making even when analysis occurs after a delay.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over by Peyser et al. (US-20070027383-A1), hereto referred as Peyser, and further in view of Sembrowich et al. (US-5036861-A), hereto referred as Sembrowich, and further in view of Heikenfeld et al. (WO-2018005438-A1), hereto referred as Heikenfeld, and further in view of Glenn et al. (US-3289671-A), hereto referred as Glenn.
The combined Peyser, Sembrowich, and Heikenfeld teaches claim 1 as described above.
Regarding claim 8, the combined Peyser, Sembrowich, and Heikenfeld does not disclose that the sweat stimulating material may include sodium chloride. Rather, the combined Peyser, Sembrowich, and Heikenfeld teaches a device comprising at least one sweat stimulating and collecting material, but does not disclose that the sweat stimulating material may include sodium chloride (Peyser, ¶[0067]). Sembrowich suggests using a salt solution for iontophoresis, but does not specify sodium chloride (Sembrowich, col. 2, ll. 63-68). Glenn teaches that a sweat stimulating material may include sodium chloride, specifically a pad saturated with a saline solution such as sodium chloride to promote good conductivity for iontophoresis (Glenn, col. 2, lines 67–72). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Glenn to include sodium chloride in the sweat stimulating material. The combination would have been feasible because both Peyser and Glenn disclose sweat stimulation and collection devices utilizing iontophoresis, and it would have been obvious to substitute or supplement the sweat stimulating material of Peyser with sodium chloride as taught by Glenn, since sodium chloride is a common and well-known electrolyte for improving conductivity in iontophoresis systems. The benefit of this combination would be to enhance the efficiency and reliability of sweat stimulation via iontophoresis by promoting good conductivity, as demonstrated in Glenn (Glenn, col. 1, lines 8–12; col. 2, lines 67–72).
Claims 9-10 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Peyser et al. (US-20070027383-A1), hereto referred as Peyser, and further in view of Sembrowich et al. (US-5036861-A), hereto referred as Sembrowich, and further in view of Heikenfeld et al. (WO-2018005438-A1), hereto referred as Heikenfeld, and further in view of Berner et al. (US-20030195403-A1), hereto referred as Berner.
The combined Peyser, Sembrowich, and Heikenfeld teaches claim 1 and claim 29 as described above.
Regarding claim 9, the combined Peyser, Sembrowich, and Heikenfeld does not fully teach that the system comprises a housing, wherein the iontophoresis electrode, second iontophoresis electrode, at least one sweat stimulating and collecting material, and sweat stimulating iontophoresis material are disposed at least partially within the housing. Rather, the combined Peyser, Sembrowich, and Heikenfeld teaches a housing, iontophoresis electrode, second iontophoresis electrode, at least one sweat stimulating and collecting material, and sweat stimulating material as shown in claim 7 above, but does not disclose that the iontophoresis electrode, second iontophoresis electrode, at least one sweat stimulating and collecting material, and sweat stimulating material are disposed at least partially within the housing. Berner teaches that the iontophoresis electrodes (12 and 14), sweat collecting reservoirs (4 and 6) containing conductive mediums (8 and 10), and sweat stimulating materials (preferably cylindrical hydrogel pads) are assembled together and disposed within a housing (housing 32), which is shown in exploded view in Figure 2. The housing is described as a plastic case or other suitable structure that is configured to be worn on the subject's arm in a manner similar to a wrist watch. When assembled, the conductive media are in contact with the electrodes and are contained within the housing, providing an operational iontophoretic sampling device with all key components at least partially within the housing (Berner, ¶[0093]–[0094]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, and Heikenfeld in view of Berner to dispose the iontophoresis electrode, second iontophoresis electrode, at least one sweat stimulating and collecting material, and sweat stimulating material at least partially within the housing, as taught by Berner. The combination would have been feasible because both references describe wearable sweat sampling and stimulation devices, and it would have been obvious to incorporate Berner's configuration of integrating all necessary components into a single, unitary, wearable housing for improved convenience, user comfort, and protection of device elements. The benefit of this combination would be a more robust, user-friendly, and portable sampling device (Berner, ¶[0094]).
Regarding claim 10, the combined Peyser, Sembrowich, Heikenfeld, and Berner does not teach that the at least one sweat stimulating and collecting material is adapted to be removable from the housing. Rather, the combined Peyser, Sembrowich, Heikenfeld, and Berner teaches a device comprising at least one sweat stimulating and collecting material, but does not disclose that the sweat stimulating and collecting material is adapted to be removable from the housing (as shown above in claim 9). Berner teaches that the sweat stimulating and collecting material (hydrogel pads) are separable and adapted to be removably placed within the housing of the device (Berner, ¶[0094]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Peyser, Sembrowich, Heikenfeld, and Berner in view of Berner to adapt the sweat stimulating and collecting material to be removable from the housing, as taught by Berner. The com