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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-13 and 18-20, in the reply filed on 01/02/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 14-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/02/2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/12/2023, 05/19/2023, and 06/14/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 2, 4, 6, 10-11, and 13 are objected to because of the following informalities:
In claim 2, it is believed “implanted microfluidic device” should read “implantable microfluidic device”.
In each of claims 4 and 6, change “implantable device” to “implantable microfluidic device” for consistency with claim 1.
In each of claims 10, 11, and 13, it is believed “being injecting” should read “being injected”.
In each of claims 10, 11, and 13, change “microfluidic implantable device” to “implantable microfluidic device” for consistency with claim 1.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
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 4-5, 7-13, and 20 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 4 recites the limitation "the difference of pressure" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the inlet and the outlet of the implantable device" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites “selected from the group comprising…culture media, oxygen carrier…”, which appears to be an attempt to set forth a list of alternatives from which a selection is to be made (typically referred to a Markush claim). It has been held that “If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim.” (see MPEP 2173.05(h)). Therefore, claim 7 is indefinite due to the “comprising” language of the Markush grouping.
Claim 7 recites the limitation "the circulating system" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the liquid secreted by the ex-vivo skin explant" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the output port" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the collected fractions" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the at least one biomarker of interest" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the step (g) of connecting the tubings to a circulating system" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "the step (h) of collecting the liquid secreted by the ex-vivo skin explant" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the at least one compound of interest" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the step (g) of connecting the tubings to a circulating system" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation “the step (h) of collecting the liquid secreted by the ex-vivo skin explant" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the at least one compound of interest" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "the step (g) of connecting the tubings to a circulating system" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation “the step (h) of collecting the liquid secreted by the ex-vivo skin explant" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation “the composition being injecting in the hypodermis of the ex-vivo skin explant by using the microfluidic implantable device”; however, this is at odds with what is stated in independent claim 1, from which claim 11 depends. Claim 1 recites that the microfluidic device is inserted “through the dermis” rather than the hypodermis, and neither claim 1 nor claim 11 recites removing the microfluidic device from the dermis and inserting it through the hypodermis. Therefore, it is unclear how injection in the hypodermis by using the microfluidic device could be achieved.
Claim 12 recites the limitation "the step (g) of connecting the tubings to a circulating system" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation "the step (g) of connecting the tubings to a circulating system" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation “the step (h) of collecting the liquid secreted by the ex-vivo skin explant" in lines 4-5. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation “the composition being injecting in the dermis or hypodermis”; however, this is at odds with what is stated in independent claim 1, from which claim 13 depends. Claim 1 recites that the microfluidic device is inserted “through the dermis” rather than the hypodermis, and neither claim 1 nor claim 13 recites removing the microfluidic device from the dermis and inserting it through the hypodermis. Therefore, it is unclear how injection in the hypodermis by using the microfluidic device could be achieved.
Dependent claims are rejected for the same reason(s) as the base claim(s) upon which they depend.
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.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Descargues (US Patent Application Publication 2015/0132737) in view of Holmgaard et al. (Comparison of Open-Flow Microperfusion and Microdialysis Methodologies When Sampling Topically Applied Fentanyl and Benzoic Acid in Human Dermis Ex Vivo) (already of record).
Regarding claim 1, Descargues discloses an in-vitro method for culturing an ex-vivo skin explant (Abstract) comprising:
providing an ex-vivo skin explant comprising the epidermis, dermis, epidermal appendages, and hypodermis (para. 52-57);
immersing the skin explant in a liquid matrix capable of solidifying so that the upper surface of the epidermis is not covered (para. 79-80), which matrix is itself contained in a cell culture insert the bottom of which consists of a porous membrane (para. 16);
solidifying the matrix so as to trap the immersed part of the skin explant (para. 18), where the upper surface of the epidermis is not covered (para. 18, 79), and to cause the solidified matrix to adhere to the side walls and the porous membrane of the insert (para. 18);
putting the culture insert containing the skin explant obtained the solidifying step in a culture chamber containing appropriate culture medium (para. 17-19, 94, 146); and
culturing the skin explant (para. 94, 146).
Descargues discloses that the study of topical application of substances on cultured skin explants is experimentally valuable (para. 5, 11) and envisions applying his method for the study of topical applications on the skin explant via the uncovered epidermis (para. 133, 150).
Descargues is silent as to the method comprising inserting an implantable microfluidic device through the dermis so that the device is positioned substantially parallel to the epidermis and traverses the skin explant from side to side, both ends of the device protruding slightly beyond the skin explant and connecting the two ends of the implantable microfluidic device to two separate tubings, and wherein the hypodermis comprises between 5 and 15 mm of hypodermis.
As to the limitation regarding the implantable microfluidic device, Holmgaard et al. discloses a method of studying topical applications of substances on an ex vivo skin explant (Title, Abstract) comprising inserting an implantable microfluidic device (called probe; reads on a microfluidic device as the probe is microscale and handles microliter-scale fluid amounts) (Abstract, p. 1809 col. 2 last paragraph-p. 1811 col. 1 first paragraph, p. 1812 col. 2 first paragraph) through the dermis of an ex vivo skin explant so that the device is positioned substantially parallel to the epidermis and traverses the skin explant from side to side with both ends of the device protruding slightly beyond the skin explant (p. 1811 col. 2 second-to-last paragraph) (Figs. 1-3, pp. 1809-1812), and connecting the two ends of the implantable microfluidic device to two separate tubings (p. 1809 col. 2 last paragraph-p. 1811 col. 1 first paragraph, p. 1812 col. 2 first paragraph) (Figs. 1-3, pp. 1809-1812). Holmgaard et al. discloses that this technique allows for the study of penetration of topical substances applied to the epidermis of the skin explant via analysis of fluid collected from the microfluidic device inserted through the dermis (Abstract, p. 1811 col. 2 second paragraph-p. 1813 col. 2 last paragraph).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the method disclosed by Descargues to comprise inserting an implantable microfluidic device through the dermis so that the device is positioned substantially parallel to the epidermis and traverses the skin explant from side to side, both ends of the device protruding slightly beyond the skin explant and connecting the two ends of the implantable microfluidic device to two separate tubings, as Holmgaard et al. discloses that it was known in the art to use an implantable device in such a manner to allow for the study of penetration of topical substances applied to the skin, and the skilled artisan would have been motivated to modify the method to enable study of topical substances as envisioned by Descargues.
As to the limitation of between 5 and 15 mm of hypodermis, Descargues discloses that the skin explant comprises skin layers including the hypodermis (para. 53-57) and that the skin explant has a thickness of preferably between 2 and 10 mm (para. 66), and therefore the thickness of the hypodermis layer of the skin explant must necessarily be no more than 2 and 10 mm. Therefore, Descargues discloses a range overlapping the claimed range of between 5 and 15 mm. It has been held that in the case where a claimed range overlaps or lies inside a range disclosed by the prior art, a prima facie case of obviousness exists (MPEP §2144.05). Therefore, the noted limitation does not introduce a patentable distinction over the prior art.
Regarding claim 2, Descargues in view of Holmgaard et al. teaches a portion of the implantable microfluidic device passing through the ex-vivo skin explant, as set forth above, and Holmgaard et al. discloses wherein the portion of the implanted microfluidic device that passes through the ex-vivo skin explant is porous (p. 1809 col. 2 last paragraph-p. 1811, p. 1816 col. 2 second paragraph); therefore, the prior art combination arrives at the claimed subject matter.
Regarding claim 3, Descargues in view of Holmgaard et al. teaches the porous portion, as set forth above, and Holmgaard et al. further discloses wherein the porous portion is obtained by making pores having a microscale diameter (p. 1809 col. 2 last paragraph-p. 1811, p. 1816 col. 2 second paragraph).
However, the prior art combination does not teach the particular range of about 40 µm to about 250 µm.
Nonetheless, it has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions of the claim, as discussed above, and the skilled artisan would have recognized that the pore size affects exchange of a substance of interest across the porous portion (see p. 1816 col. 2 second paragraph of Holmgaard et al.). Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover an optimum or workable range for the pore size by routine experimentation.
Regarding claim 4, Descargues in view of Holmgaard et al. teaches the step of connecting the two ends of the implantable microfluidic device to two separate tubings, as set forth above.
Descargues is silent as to the connecting step as claimed; however Holmgaard et al. further discloses connecting the tubings to a circulating system comprising a pump for providing a continuous or discontinuous/pulsatile flow (p. 1811 col. 2 second-to-last paragraph, p. 1812 col. 2 first paragraph) (reads on the claimed means for providing a continuous or discontinuous/pulsatile flow and/or for modulating the difference of pressure between the inlet and the outlet of the implantable device, a limitation invoking 112(f) and interpreted to cover a pump, consistent with Applicant’s specification), said connecting being mediated by input and output ports at an inlet and an outlet of the implantable device (p. 1809 col. 2 last paragraph-p. 1811 col. 1 first paragraph, p. 1812 col. 2 first paragraph) (Figs. 1-3, pp. 1809-1812), wherein the connecting allows for perfusion of a fluid through the skin explant to enable a sample to be drawn to study the penetration of a topical substance applied to the skin (Abstract, p. 1811 col. 2 second paragraph-p. 1813 col. 2 last paragraph).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to further comprise connecting the tubings to a circulating system comprising a pump (reads on a means for providing a continuous or discontinuous/pulsatile flow) wherein said connecting is mediated by input and output ports at an inlet and an outlet of the implantable device, based on the teachings of Holmgaard et al., to enable fluid perfusion for collection of a sample to study topical substance penetration through the skin.
Regarding claim 5, Descargues in view of Holmgaard et al. teaches a fluid perfused within the skin explant, as set forth above, and Holmgaard et al. discloses wherein the flow rate of the fluid perfused is 1 µL/min (falls within the claim range) (p. 1812 col. 2 first paragraph); therefore, the prior art combination arrives at the claimed subject matter.
Regarding claim 6, the limitation of “the difference of pressure” is best understood as an optional limitation, as claim 4, from which claim 6 depends, recites providing a pressure difference in the alternative (“means for providing a continuous or discontinuous/pulsatile flow and/or for modulating the difference of pressure between the inlet and the outlet of the implantable device”). The prior art combination teaches another of the list of alternatives, ad discussed in the rejection of claim 4, above, and therefore claim 6 does not introduce a patentable distinction over the prior art.
Regarding claim 7, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the skin explant, as set forth above.
Descargues is silent as to a step of injecting a compound as claimed; however Holmgaard et al. further discloses injecting a perfusate comprising an electrolyte composition and/or 1% human serum albumin (reads on culture media or a drug) via a circulating system through the skin explant to enable a sample to be drawn to study the penetration of a topical substance applied to the skin (Abstract, p. 1811 col. 1 third paragraph-p. 1813 col. 2 last paragraph).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to further comprise injecting a perfusate comprising an electrolyte composition and/or 1% human serum albumin (reads on culture media or a drug) via a circulating system (thus rendering the method a method for administering a compound of interest wherein the compound is culture media or a drug), based on the teachings of Holmgaard et al., to enable fluid perfusion for collection of a sample to study topical substance penetration through the skin.
Claims 8 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Descargues (US Patent Application Publication 2015/0132737) in view of Holmgaard et al. (Comparison of Open-Flow Microperfusion and Microdialysis Methodologies When Sampling Topically Applied Fentanyl and Benzoic Acid in Human Dermis Ex Vivo) (already of record) as applied to claim 1, above, and in further view of Baumann et al. (Skin microdialysis: methods, applications and future opportunities—an EAACI position paper) (already of record).
Regarding claim 8, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the skin explant as set forth above.
Descargues is silent as to a step of collecting liquid secreted as claimed; however, Holmgaard et al. further discloses collecting liquid secreted by the ex-vivo skin explant through an output port of the implantable microfluidic device so as to study an interaction of a compound applied to the skin and the skin (Abstract, p. 1811 col. 2 second paragraph-p. 1813 col. 2 last paragraph).
Furthermore, Baumann et al. discloses that it was known in the art to use skin microdialysis to collect liquid secreted by skin following application of a drug or other stimulus, and then isolate and identify at least one biomarker of interest contained in the collected liquid to study an interaction between the skin and the drug or other stimulus (Abstract, p. 3 col. 2 last paragraph-p. 4 col. 1 second-to-last paragraph).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to comprise collecting liquid secreted by the skin explant through an outlet port of the implantable microfluidic device and isolating and identifying a biomarker of interest in the collected liquid (thus rendering the method a method for further detecting at least one biomarker of interest as claimed), based on the teachings of Holmgaard et al. and Baumann et al., to enhance the experimental utility of the method in elucidating interactions between skin and drugs and other stimuli.
Regarding claim 10, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the dermis of the skin explant as set forth above.
Descargues is silent as to injecting a composition and collecting liquid secreted by the skin explant as claimed; however, Holmgaard et al. further discloses applying a topical composition to the skin explant after connecting the tubings to a circulating system (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph) and subsequently collecting liquid secreted by the skin explant to determine an interaction between the composition and the skin (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph).
Furthermore, Baumann et al. discloses that it was known in the art to use skin microdialysis techniques to study the effects of injected compositions as well as topical compositions (Abstract) and specifically discloses that it was known in the art to inject a composition comprising at least one compound of interest via the probe of a skin microdialysis system to study an interaction between the at least one compound of interest and skin (p. 3 col. 1 para. 2).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to comprise injecting a composition comprising at least one compound of interest after connecting the tubings to a circulating system and prior to collecting liquid secreted by the skin explant, the composition injected in the dermis by using the microfluidic implantable device (thus rendering the method a method for assessing the activity of at least one compounds intradermally injected as claimed), based on the teachings of Holmgaard et al. and Baumann et al., in order to enhance the experimental utility of the method in elucidating interactions between skin and injected compounds of interest.
Regarding claim 11, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the dermis of the skin explant as set forth above.
Descargues is silent as to injecting a composition and collecting liquid secreted by the skin explant as claimed; however, Holmgaard et al. further discloses applying a topical composition to the skin explant after connecting the tubings to a circulating system (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph) and subsequently collecting liquid secreted by the skin explant to determine an interaction between the composition and the skin (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph).
Furthermore, Baumann et al. discloses that it was known in the art to use skin microdialysis techniques to study the effects of injected compositions as well as topical compositions (Abstract) and specifically discloses that it was known in the art to inject a composition comprising at least one compound of interest via the probe of a skin microdialysis system to study an interaction between the at least one compound of interest and skin (p. 3 col. 1 para. 2).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to comprise injecting a composition comprising at least one compound of interest after connecting the tubings to a circulating system and prior to collecting liquid secreted by the skin explant, the composition injected in the dermis by using the microfluidic implantable device (thus rendering the method a method for assessing the activity of at least one compounds injected as claimed), based on the teachings of Holmgaard et al. and Baumann et al., in order to enhance the experimental utility of the method in elucidating interactions between skin and injected compounds of interest. As to the limitation of the composition being injected in the hypodermis, Holmgaard et al. discloses wherein the microfluidic device is inserted through the dermis, as discussed above, and therefore it is understood that a composition injected via the microfluidic device would permeate to the hypodermis, which is adjacent to the dermis.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Descargues (US Patent Application Publication 2015/0132737) in view of Holmgaard et al. (Comparison of Open-Flow Microperfusion and Microdialysis Methodologies When Sampling Topically Applied Fentanyl and Benzoic Acid in Human Dermis Ex Vivo) (already of record) as applied to claim 1, above, and in further view of National Cancer Institute (Skin Cancer Treatment (PDQ®)).
Regarding claim 9, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the skin explant as set forth above.
Descargues is silent as to applying a topical composition and collecting liquid secreted as claimed; however, Holmgaard et al. further discloses applying a topical composition to the epidermis after connecting the tubings to a circulating system (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph) and subsequently collecting liquid secreted by the skin explant to determine penetration of the composition through the skin (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph).
Furthermore, National Cancer Institute discloses that it was known in the art of skin treatment to apply biomarkers topically to treat skin conditions (“Biologic therapy”, p. 21).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to comprise applying topically to the epidermis of the skin explant a composition comprising at least one biomarker of interest after connecting the tubings to a circulating system and prior to collecting liquid secreted by the skin explant (thus rendering the method a method for assessing permeation of at least one biomarker of interest as claimed), based on the teachings of Holmgaard et al. and National Cancer Institute, to enhance the experimental utility of the method in studying skin penetration of topical biologic drugs.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Descargues (US Patent Application Publication 2015/0132737) in view of Holmgaard et al. (Comparison of Open-Flow Microperfusion and Microdialysis Methodologies When Sampling Topically Applied Fentanyl and Benzoic Acid in Human Dermis Ex Vivo) (already of record) as applied to claim 1, above, and in further view of Van Der Merwe et al. (US Patent Application Publication 2003/0180942).
Regarding claim 12, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the skin explant as set forth above.
Descargues is silent as to injecting an oxygen carrier as claimed; however, Holmgaard et al. further discloses injecting a perfusion fluid for perfusing through the skin explant after a step of connecting the tubings to a circulating system (p. 1811 col. 1 third paragraph-p. 1813 col. 2 last paragraph).
Furthermore, Van Der Merwe et al. discloses using a perfusion fluid comprising an oxygen carrier while perfusing living cells in order to support metabolic function of the living cells (Abstract, para. 6).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the method taught by Descargues in view of Holmgaard et al. to comprise injecting an oxygen carrier after connecting the tubings to a circulating system (thus rendering the method a method for oxygenating the ex-vivo skin explant as claimed), based on the teachings of Holmgaard et al. and Van Der Merwe et al., in order to support the metabolic functioning of the skin explant.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Descargues (US Patent Application Publication 2015/0132737) in view of Holmgaard et al. (Comparison of Open-Flow Microperfusion and Microdialysis Methodologies When Sampling Topically Applied Fentanyl and Benzoic Acid in Human Dermis Ex Vivo) (already of record) as applied to claim 1, above, and in further view of De Kock et al. (Inflammation Alters the Secretome and Immunomodulatory Properties of Human Skin-Derived Precursor Cells).
Regarding claim 13, Descargues in view of Holmgaard et al. teaches inserting the implantable microfluidic device into the dermis of the skin explant as set forth above.
Descargues is silent as to applying a topical composition and collecting liquid secreted as claimed; however, Holmgaard et al. further discloses applying a topical composition to the epidermis after connecting the tubings to a circulating system (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph) and subsequently collecting liquid secreted by the skin explant to determine an interaction of the composition with the skin (p. 1811 col. 2 second-to-last paragraph-p. 1813 col. 2 last paragraph).
Furthermore, De Kock discloses that understanding the inflammation state of skin explants is of great clinical importance (Abstract) and further discloses a method comprising treating a skin cell sample with a composition comprising a cocktail of pro-inflammatory cytokines and subsequently collecting cell secretions to analyze an inflammation response (p. 3 para. 2, p. 4 para. 1-3).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to further modify the method taught by Descargues in view of Holmgaard et al. to comprise injecting a composition comprising a cocktail of pro-inflammatory cytokines after connecting the tubings to a circulating system and prior to collecting liquid secreted by the skin explant, the composition being injected in the dermis using the microfluidic device (thus rendering the method a method for studying inflammation of skin as claimed), based on the teachings of Holmgaard et al. and De Kock, to enhance the experimental utility of the method in studying skin inflammation response.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Takeuchi et al. (US Patent Application Publication 2017/0274121) is directed to a system for perfusing artificial skin tissue including a channel traversing the skin tissue from side to side through the dermal tissue layer.
Strüver et al. (Development of a Perfusion Platform for Dynamic Cultivation of in vitro Skin Models) is directed to a method of culturing a skin model in a perfusion platform comprising a cell culture insert and connected to a peristaltic pump.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOLLY KIPOUROS whose telephone number is (571)272-0658. The examiner can normally be reached M-F 8.30-5PM.
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799