DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a 371 of PCT/US2022/075191, filed 8/19/2022. This application claims benefit to U.S. Provisional Application Serial Number 63/370,751, filed 8/08/2022 and Serial Number 63/235,371, filed 8/20/2021. Claims 1-41 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-6 and 13-40 in the reply filed on 5/13/2026 is acknowledged. Claims 7-12 and 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/13/2026.
The traversal (Remarks, pp. 2-3) is on the grounds that a) the administered composition in Descargues is not a therapeutic compound product and b) that it would not be a search burden to examine the claims of Groups II and III at the same time as examining the claims of Group I. Traversal ‘b’ is not found persuasive because the restriction requirement is based on lack of unity of invention of this national stage application (371) of an international application (see 37 C.F.R. 1.499). Search burden is not a consideration when determining lack of unity of invention in national stage applications; hence, Applicant’s traversal based on search burden is unpersuasive.
Regarding Applicant’s allegation that the injected composition of tumor necrosis factor alpha (TNFa) and lipopolysaccharide (LPS) in Descargues does not contain any therapeutic compound (Remarks, pp. 2-3), tumor necrosis factor alpha (TNFa) is disclosed as a therapeutic compound in the instant disclosure (specification, p. 11, l. 34; PG-Pub, [0043]). Hence, Applicant’s allegation that the injected composition in Descargues does not contain any therapeutic compound is thoroughly unpersuasive as the injected composition in Descargues comprises tumor necrosis factor alpha (TNFa) which is listed as a therapeutic compound in the instant disclosure.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statements submitted on 2/16/2024 and 6/24/2026 have been considered by the examiner.
Claim Objections
Claim 18 is objected to because of the following informalities:
Claims are to be complete sentences. Claim 18 is missing a period. 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 19-20 and 22 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.
The terms “proximal substrate” and “distal substrate” in claims 19 and 20 are relative terms which renders the claim indefinite. The terms “proximal substrate” and “distal substrate” are indefinite because what the substrates are proximal or distal to is not defined by the claim and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention; hence, claims 19-20 are rejected under 35 U.S.C. 112(b) as being indefinite.
Regarding claim 22, the phrase "detecting a presence of level of subvisible particles" renders the claim indefinite because it is unclear whether the detecting is of the presence of subvisible particles or quantifying the amount of subvisible particles; hence, claim 22 is rejected under 35 U.S.C. 112(b) as being indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-6 and 13-40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 1-6 and 13-40 are drawn to methods comprising a mental step, i.e., a judicial exception, without significantly more.
The first question in the subject matter eligibility determination is “Is the claim to a process, machine, manufacture or composition of matter?” (Step 1)
Yes, claims 1-6 and 13-40 are drawn to methods, i.e., a process.
The second question (Step 2A, prong 1) in the subject matter eligibility determination asks “Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)?"
Yes, the claimed processes are drawn to processes comprising an abstract idea (mental step; judicial exception) and well understood, conventional and routine laboratory steps.
Regarding claims 1-6 and 13-40, the processes are drawn to selecting a condition of administration for a therapeutic compound product for subcutaneous administration comprising selecting or rejecting a condition of administration for further development based on the detected physiochemical and/or clinical characteristic of the therapeutic compound after administering the therapeutic compound to a live mammalian skin dermal/epidermal interface under a condition of administration, i.e., a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Step 2A, prong 2 asks “Does the claim recite additional elements that integrate the judicial exception into a practical application?”
Regarding claims 1-6 and 13-40, no, the claims do not integrate the judicial exception into a practical application because the claims do not recite any practical steps to be taken upon making the mental step of whether the candidate compound is suitable for the prevention and/or treatment of the disease or the mental step of determining a diagnosis, prognosis, stratification and/or monitoring of a therapy, of the disease in the subject.
The final question (Step 2B) in the subject matter eligibility determination to be asked is “Does the claim recite additional elements that amount to significantly more than the judicial exception?”
No, claims 1-6 and 13-40 do not recite additional elements that amount to significantly more than the judicial exception.
The live in vitro mammalian skin, administration of a therapeutic compound to the interface of the construct and detecting a physiochemical and/or clinical characteristic of the therapeutic compound after the administration are well-understood, routine and conventional techniques as detailed in the art rejections below.
These well-understood, routine, conventional activities are not part of a specific transformative method, but rather represent generalized method steps which are executed solely for the production of data for the mental step. Accordingly, claims 1-6 and 13-40 do not amount to significantly more than the judicial exceptions and are not patent eligible.
Thus, claims 1-6 and 13-40 are rejected under U.S.C. 101 as not being drawn to patent eligible subject matter.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-6, 13-20, 22-24, 27-28 and 30-40 are rejected under 35 U.S.C. 103 as being unpatentable over Kinderman et al., 2019 (NPL cite 1, IDS, 6/24/2026; herein “Kinderman”) in view of Descargues et al., US 2020/0400652 (US Patent Application Publication cite 1, IDS, 2/16/2024; herein “Descargues”).
Kinderman discloses methods of assessing the immunogenicity, i.e., a physiochemical and/or clinical characteristic of the therapeutic compound product in the interface, of subcutaneous administration of a therapeutic compound product based on a condition of administration, i.e., the concentration of the therapeutic and the formulation of the therapeutic, comprising administering a therapeutic compound product to the dermal/epidermal interface under a condition of administration, i.e., the concentration of the therapeutic and the formulation of the therapeutic; detecting a physiochemical and/or clinical characteristic of the therapeutic compound product in the interface, i.e., concentration-dependent precipitation of the therapeutic at the injection site and immunogenicity risk (Abst.) which a person of ordinary skill in the art at the time of filing would have found would obviously allow the selecting or rejecting the condition of administration for further development based on the detected physiochemical and/or clinical characteristic of the therapeutic compound.
Kinderman differs from the instant claims in that Kinderman administers the therapeutic compound subcutaneously to the dermal/epidermal interface in living mice whereas the instant claims require that the subcutaneous administration to the dermal/epidermal interface is in a live in vitro mammalian skin. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the subcutaneous administration to be to the dermal/epidermal interface in a live in vitro mammalian skin in view of the disclosure of Descargues.
Descargues teaches an ex vivo, i.e., in vitro, model for subcutaneous injection, comprising epidermis, dermis, interface therebetween and hypodermis over a porous membrane (Abst.) Descargues teaches that the skin explant can be human skin or pig skin [0037].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of Kinderman using Descargues live in vitro mammalian skin model for the subcutaneous injection in order to select or reject the condition of administration for further development based on the detected physiochemical and/or clinical characteristic of the therapeutic compound because it would reduce the number of animals sacrificed for the study; therefore, claims 1-6, 13-20, 22-25, 27-28 and 30-40 are prima facie obvious.
Regarding claim 2, a condition of administration in Kinderman comprises concentration of the therapeutic (Abst.); hence, a person of ordinary skill in the art at the time of filing would have found it obvious for concentration of the therapeutic to be a condition of administration in the method made obvious by Kinderman in view of Descargues; therefore, claim 2 is prima facie obvious.
Regarding claim 3, a condition of administration in Kinderman comprises a buffer because Kinderman teaches that adding phosphate buffered saline at neutral pH caused precipitation of an antibody therapeutic (p. 1956, “Development of an Assay to Predict In Vivo Aggregation”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for a buffer of the therapeutic formulation to be a condition of administration in the method made obvious by Kinderman in view of Descargues; therefore, claim 3 is prima facie obvious.
Regarding claim 4, Kinderman teaches that a physiochemical and/or clinical characteristic of the therapeutic compound product in the interface is precipitation as subcutaneous injection of some therapeutics drives precipitation of the therapeutic when it encounters the neutral pH of the interstitial fluid (p. 1956, “Development of an Assay to Predict In Vivo Aggregation”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for precipitation to be a physiochemical and/or clinical characteristic of the therapeutic compound product in the interface in the method made obvious by Kinderman in view of Descargues; therefore, claim 4 is prima facie obvious.
Regarding claim 5, Kinderman teaches that a physiochemical and/or clinical characteristic of the therapeutic compound product in the interface is precipitation as subcutaneous injection of some therapeutics drives precipitation of the therapeutic when it encounters the neutral pH of the interstitial fluid (p. 1956, “Development of an Assay to Predict In Vivo Aggregation”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the therapeutic compound product acquired the physiochemical and/or clinical characteristic after said administering in the method made obvious by Kinderman in view of Descargues; therefore, claim 5 is prima facie obvious.
Regarding claim 6, Kinderman teaches that the precipitation of the pH-sensitive antibody, i.e., therapeutic, and retention at the injection site is dependent on the concentration of the therapeutic and assays subcutaneous injections of multiple concentrations of the therapeutic (pp. 1957-1958, “Assessing the Impact of Antibody Retention on Pharmacokinetics and Immunogenicity”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the method made obvious by Kinderman in view of Descargues comprises repeating the method for two or more different conditions of administration; therefore, claim 6 is prima facie obvious.
Regarding claims 13, 15 and 17, a person of ordinary skill in the art at the time of filing would have found it obvious that the subcutaneous administration of the therapeutic composition to the dermal/epidermal interface would comprise pressing a needle comprising a cannula to a surface of the dermal layer, thereby inserting the needle in the interface of the live in vitro mammalian skin; and disposing the therapeutic compound product in the subcutaneous space via the needle, wherein the needle comprises an opening in fluid communication with the cannula, wherein administering comprises orienting the opening toward the dermal layer, wherein the administration is transdermal; therefore, claims 13, 15 and 17 are prima facie obvious.
Regarding claim 14, Descargues teaches that the subcutaneous injections into the in vitro living skin model comprises making a skin fold for the injection ([0010], [0028], [0127]). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the method made obvious by Kinderman in view of Descargues comprises pressing the needle against the dermal surface at an acute angle; therefore, claim 14 is prima facie obvious.
Regarding claims 18, 23 and 25, Descargues teaches that the in vitro mammalian live skin model comprises hypodermis (Abst.) and that the in vitro mammalian live skin model comprises human skin or pig skin [0037]. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein the in vitro mammalian skin further comprises a hypodermis that defines a subcutaneous space within the interface, wherein the in vitro mammalian skin is an in vitro human skin or wherein the in vitro mammalian skin is of a non-human mammal; therefore, claims 18, 23 and 25 are prima facie obvious.
Regarding claim 24, non-human primates are used as research models as a substitute for humans; hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein the in vitro mammalian skin is from a non-human primate research model; therefore, claim 24 is prima facie obvious.
Regarding claims 30-32, Kinderman teaches that the therapeutic composition comprises antibody labeled with a fluorophore (pp. 1957-1958, “Assessing the Impact of Antibody Retention on Pharmacokinetics and Immunogenicity”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein the therapeutic composition comprises antibody labeled with a fluorophore; therefore, claims 30-32 are prima facie obvious.
Regarding claims 39-40, Descargues teaches that the live in vitro mammalian skin is provided in media (Abst.). Descargues does not disclose that the media has been filtered with a centrifuge filter having a molecular weight cutoff of no more than 50 kDa; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein the media for the skin explant has been filtered to maintain sterility and/or to concentrate the medium wherein a centrifuge filter having a molecular weight cutoff of no more than 50 kDa would be an obvious filtration method; therefore, claims 39-40 are prima facie obvious.
Regarding claims 19-20, Kinderman teaches that the subcutaneous injection sites of the mice were surgically explanted and either 1) placed in a glass-bottom dish for ex vivo multiphoton imaging or 2) embedded and mounted with glass coverslips for confocal fluorescence microscopy (p. 1955, “Ex Vivo Multiphoton Imaging”, “Confocal Fluorescence Microscopy”).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein the in vitro mammalian skin is immobilized between proximal and distal glass substrates; therefore, claims 19-20 are prima facie obvious.
Regarding claim 33, Kinderman teaches analytical testing of the therapeutic composition before administration (p. 1956, “Development of an Assay to Predict In Vivo Aggregation”); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues comprising performing analytical testing on the therapeutic compound prior to said administering; therefore, claim 33 is prima facie obvious.
Regarding claim 34, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein said detecting comprises obtaining a background signal and subtracting the background signal because background subtraction is necessary in any scientific methodology to correctly remove the background from the signal; therefore, claim 34 is prima facie obvious.
Regarding claim 21, Descargues teaches that the skin explant is on a porous membrane (Abst.). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein providing the in vitro mammalian skin comprises providing the dermal layer of the skin model disposed on a porous substrate that comprises pores sized to accommodate diffusion of the therapeutic compound product, and wherein said administering comprises placing the porous substrate in fluid communication with a solution comprising the therapeutic compound product; therefore, claim 21 is prima facie obvious.
Regarding claims 16, 27-28 and 35-37, Kinderman teaches optically imaging the injection site with multiphoton laser scanning microscopy comprising second-harmonic generation (SHG) imaging (p. 1955, “Ex Vivo Multiphoton Imaging”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein detecting comprises optical imaging through the dermal layer wherein the optical imaging comprises multiphoton laser scanning microscopy and second-harmonic generation imaging; therefore, claims 16, 27-28 and 35-37 are prima facie obvious.
Regarding claim 22, Kinderman teaches visualizing 2-15 µm particles, i.e., subvisual, with multiphoton laser scanning microscopy at the injection site (pp. 1957-1958, “Assessing the Impact of Antibody Retention on Pharmacokinetics and Immunogenicity”); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues comprising detecting a presence of level of subvisible particles in the solution after said administering; therefore, claim 22 is prima facie obvious.
Regarding claim 38, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein administering the therapeutic compound comprises disposing the therapeutic compound product in the subcutaneous space via the needle, and wherein the needle remains disposed in the subcutaneous space during said imaging because leaving the needle disposed would allow registration of the injection site with the needle; therefore, claim 38 is prima facie obvious.
Claims 1-6, 13-20, 22-28 and 30-40 are rejected under 35 U.S.C. 103 as being unpatentable over Kinderman in view of Descargues and Santer et al., 2018 (cite U, attached PTO-892; herein “Santer”).
The discussion of Kinderman and Descargues regarding claims 1-6, 13-20, 22-25, 27-28 and 30-40 set forth in the rejection above is incorporated herein.
Although Descargues recites using human or pig live in vitro skin to study subcutaneous injections, neither Kinderman nor Descargues specifically teach performing the method in non-human mammalian skin, repeating the method with human skin and comparing the results; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues using non-human mammalian skin, repeating the method with human skin and comparing the results in view of the disclosure of Santer.
Santer teaches studying subcutaneous injection of therapeutic compositions in porcine skin and in human skin and comparing the biophysical properties of the injections across species (Abst.).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues using non-human mammalian skin, repeating the method with in vitro human skin and comparing physiochemical and/or clinical characteristics of the therapeutic compound administered to the in vitro human skin with those of the therapeutic compound administered to the in vitro mammalian skin i-s of the non-human mammal; therefore, claim 26 is prima facie obvious.
Claims 1-6, 13-20, 22-25 and 27-40 are rejected under 35 U.S.C. 103 as being unpatentable over Kinderman in view of Descargues and Danysz et al., US 2022/0218739 (cite A, attached PTO-892; herein “Danysz”).
The discussion of Kinderman and Descargues regarding claims 1-6, 13-20, 22-25, 27-28 and 30-40 set forth in the rejection above is incorporated herein.
Neither Kinderman nor Descargues teach using computed tomography (CT) scanning or magnetic resonance imaging (MRI) for imaging in the method; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the imaging to comprise CT scanning in view of Danysz.
Danysz teaches the subcutaneous injection of a therapeutic to dissolve Radiesse® dermal filler wherein the changes in volume and density over time are monitored with CT scanning [0231].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Kinderman in view of Descargues wherein the imaging comprises CT scans; therefore, claim 29 is prima facie obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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