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 .
Status of the Claims
Claims 1-15 are pending.
Claims 1-15 have been examined on their merits.
Claim Objections
Claim 1 is objected to for the following informalities: claim 1 step b) recites “b) of mounting.” The preposition “of” is unnecessary, and this should simply be “b) mounting”, to make the clause active and bring it into grammatical conformity with the rest of the claim.
Claim 5 is objected to for the following informalities: the claim recites sub steps with both opening and closing parentheses (e.g., “step (a)”) while stylistically in the earlier claims only a closing parenthesis us used (e.g., “step a)” as in claim 1). For consistency, the claims should use the format already established in claim 1.
Claims 8 and 9 are likewise objected to for inconsistently using both opening and closing parentheses (e.g., “step (a)”).
Claim Interpretation
Claim 1 recites steps “a) injecting (a skin biopsy) . . . a’) of mounting (the injected skin biopsy) . . . b) incubating the injected skin biopsy obtained in step a).”
Therefore, step b) sequentially occurs after step a). However, specifically step b) states that this occurs after “step a)” generically, and therefore, may, but does not necessarily require step a’) which is a sub-step of step a).
It is also noted that step a’) is not required for any other specific step.
Therefore, because step a’) is a sub step, because step b) can be performed generically after step a), and because step a’) is not specifically requires in any subsequent step, step a’) is considered optional.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “the model of inflamed skin” in steps c) and d) of claim 1. Claim 15 also recites “the skin model.” There is insufficient antecedent basis for this limitation in the claim because a model of inflamed skin is not established in any of the prior steps. While the preamble of claim 1 recites “An in vitro method for evaluating the anti-inflammatory efficacy of a compound in an ex vivo model”, the recitation of “the model of inflamed skin” in steps c) and d) still lacks antecedent basis because it is unclear in which step there is a model of inflamed skin (i.e., what is considered an inflamed model). Additionally, while step c) further states “the model of inflamed skin obtained at the end of step b)” (implying that there can be a model of inflamed skin after step b)), step d) does not establish a subsequent step. Therefore, taken together, it is unclear when a model of inflamed skin is established.
Claim 1 also recites “better” which is a relative term which renders the claim indefinite. The term “better” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For compact prosecution any amount of activation is considered “better.”
Claim 6 recites “the at least one mixture” of the composition used in step b). The claim is indefinite because step b) only establishes “a mixture” and therefore, it is unclear if the “at least one mixture” refers to that mixture or another possible mixture. For compact prosecution, it has been interpreted as referred to the mixture established in step b).
Claim 2-15 are rejected under 35 USC 112(b) for their dependency on claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 14 and 15 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being in improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 14 states that “wherein the steps b) and c) are carried out simultaneously.” However, independent claim 1 step c) requires “contacting . . . the model of inflamed skin obtained at the end of step b)” and therefore requires performing step b) before step c). Therefore, claim 14, which carries out these steps simultaneously, is not further limiting.
Claim 15 states “wherein the step c) . . . takes places prior to steps a) of activating and b) of polarizing.” However, independent claim 1 step c) requires “contacting . . . the model of inflamed skin obtained at the end of step b).” Additionally, step b) requires “incubating the injected skin biopsy obtained in step a).” Therefore, claim 1 requires the sequence of steps a), b), and c), and as a result, performing step c) prior to a) and b) in claim 15 is not further limiting.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Applicant is directed to the subject matter eligibility test for products processes (MPEP 2106; specifically, MPEP 2106(III) flowchart).
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory category of invention (Step 1), if so, then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, Prong One), if so, then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, Prong Two), and if not, then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to Step 1, claims 1-15 are drawn to a process, “a method”, which is a statutory category (thus, Step 1, YES).
In regard to Step 2A, Prong One, this part of the eligibility analysis evaluates whether the claim recites a judicial exception.
Claim 1 recites “An in vitro method for evaluating the anti-inflammatory efficacy of a compound in an ex vivo model of inflamed skin. The method comprises the steps a) injecting, a’) of mounting (i.e., mounting), b) incubating, c) contacting, d) measuring, e) comparing, and f) identifying.
Steps of measuring, comparing, and identifying “can be performed in the human mind, or by a human using a pen and paper” (CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011)). Therefore, claim 1 recites a mental process, which is a judicial exception.
As discussed in MPEP 2106.04(a)(2)(III), “[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work” (Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012), quoting Benson, 409 U.S. at 67, 175 USPQ at 675)) (thus, Step 2A, Prong One, YES).
In regards to Step 2A, Prong Two, this part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception.
With respect to Step 2A, prong two, limitations that may be enough to qualify as additional elements that integrate the judicial exception into a practical application include:
Improvements to another technology or technical field.
Improvements to the functioning of the computer itself.
Applying the judicial exception with, or by use of, a particular machine.
Effecting a transformation or reduction of a particular article to a different state or thing
Adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application.
Other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
With respect to Step 2A, prong two, limitations that were found not to be enough to qualify as additional elements that integrate the judicial exception into a practical application include:
Adding the words ‘‘apply it’’ (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well understood, routine and conventional activities previously known to the industry
Adding insignificant extra-solution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea
Generally linking the use of the judicial exception to a particular technological environment or field of use.
In the instant claim 1, although the claims recite steps injecting into a reticular dermis biopsy a composition comprising an effective amount of anti-CD3 antibody and anti-CD28 antibody to activate dermal resident T cells (step a); mounting the injected skin biopsy in a cell culture insert (step a’); incubating the skin biopsy skin biopsy in a composition comprising IL-1β, etc. (step b); and contacting the model of inflamed skin obtained at the end of step b) with a candidate compound (step c), these steps all built up to the final steps of measuring, comparing, and identifying in steps d), e), and f) respectively.
Therefore, method steps a), a’), b), and c) are all insignificant extra-solution activity and amount to mere gathering for the mental process (the judicial exception). See MPEP 2106.05(g), determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)). Therefore, the claim does not additional elements that integrate the judicial exception as a whole into a practical application (thus, Step 2A, Prong Two, NO).
In regard to Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the judicial exception.
As discussed above, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception, but rather, are all mere data gathering steps for a final step of the mental processes of measuring, comparing, and identifying.
Furthermore, the additional elements of comprising treating ex vivo mammalian skin biopsies with anti-CD3/CD28 antibodies for the activation of resident T cells (step a)); performing the method on ex vivo on porous membrane inserts (step a’)); incubating skin biopsies with cytokines comprising least IL-1b, IL-23, and TGF-b to derive Th1 and Th17 polarized cells (step b)); and testing candidate compounds (step c)), for the purpose of measuring and comparing expression markers and identifying the efficacy of compounds were all routine in the art in the art before the effective filing date.
Specifically, Cote-Sierra (WO2014182655A1) evidences methods comprising taking ex vivo human skin samples, activating Th17 cells with exposure or incubation with CD3/CD28 and cytokines (e.g., TGFβ), mounting the skin to a transwell, liquid-air interface (i.e., to a culture insert the bottom of which consists of a porous membrane), contacting skin with a test compound for the purpose of measuring the production of pro-inflammatory cytokines (markers, e.g., IL17a and IL22) as compared to controls (Claims 1-7; Fig. 2A) and determining whether the compound can be used for treatment (thus, efficacy; claim 7).
This is further confirmed by Fujiyama et al. (J Allergy Clin Immunol, 2016, on IDS 07/19/2024) who evidences methods for taking ex vivo mammalian skin biopsies, incubating those biopsies with anti-CD3/CD28 antibodies and cytokines (including IL-23, and TGF-β) to expand T cells including Th17 and Th1 sub-types, and contacting those biopsies with test compounds in order to measure, compare, and identify markers (e.g., IL-17A) associated with inflammation (Abstract, p517; Methods, p518; Fig.8, p526; Induction of Th1/Th2/Th17 cells, p528.e1) where known in the art before the effective filing date.
This is confirmed by Descargues (US20150132737A1, on IDS 07/19/2024), who evidences methods comprising taking healthy ex vivo mammalian skin biopsies specifically, mounting those biopsies in an insert whose bottom is made of a porous membrane and testing candidate compounds for the purpose of highlighting a physiological or morphological modification associated with the efficacy of treatment and selecting a compound if the modifications obtained are those requested for the treatment of a disorder (claims 1 and 22-23).
This is further confirmed by Hashizume et al. (Acta Dermato-Venereologica, 2010, on IDS 07/19/2024) who evidences methods comprising taking healthy mammalian skin biopsies, incubating those biopsies with anti-CD3/CD28 antibodies and cytokines to expand T cells (Title, Abstract, p468; Table 1; p469) which can be used to measure cellular response when tested against inflammatory compounds (Relevance of lymphocytes derived from inflammatory skin lesions, 471; Fig. 4, p471).
This is further confirmed by Vielhaber et al. (EP2019316B1, 2009, on IDS 07/19/2024) who evidences methods of taking ex vivo human skim samples for modelling, simulating or analyzing a selected effect of a selected treatment by observing the effects of a substance applied to the skin (claims 1 and 3) and assessing immunestimulation or immunesuppression (claim 10), which a person of ordinary skill in the art would have recognized measures inflammation.
Furthermore, evidenced by Stoitzner et al. (Experimental Dermatology, 2014), it was known in the art that antibodies could be injected into skin biopsies (Abstract, p909; Administration of targeting antibodies to human skin, p910).
Additionally, as evidenced by Mailer et al. (Scientific Reports, 2015, on IDS 07/19/2024), it is known in the art that the cytokine IL-1β can be used in vitro to promote differentiation of naïve T cells to Th17 cells (Abstract, p1; Fig. 2, p4).
As a result, the additional elements individually or in combination with the judicial exception were routine in the art, and therefore, do not provide an inventive concept, and therefore, the claim as a whole does not amount to significantly more than the judicial exception (thus, Step 2B: NO).
Regarding dependent claims 2-15, the claims neither add additional elements that are sufficient to amount to significantly more than the judicial exception (e.g., the claims are directed to routine or conventional embodiments of the data gathering steps).
Therefore, the claims are not considered to recite something significantly different than a judicial exception and thereby are not directed to patent eligible subject matter.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US12071648B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant invention and the patent are drawn to an in vitro method for evaluating the anti-inflammatory efficacy of a compound in an ex vivo model of inflamed skin comprising a) injecting a first composition, using a hollow needle into the reticular dermis of a healthy mammalian skin biopsy having a thickness of 3 mm to 1 cm, which is a mammalian skin fragment comprising at least the epidermis, the dermis, the epidermal appendages and a portion of the hypodermis, wherein the first composition comprises an effective amount of an anti-CD3 antibody and an anti-CD28 antibody for activating dermal resident T cells, thus allowing homogeneous diffusion of the first composition into all tissues of the biopsy, and activation of the resident T cells of the dermis in the injected mammalian skin biopsy; a′) mounting the injected mammalian skin biopsy obtained at the end of step a) in a cell culture insert the bottom of which consists of a porous membrane and said insert being arranged in a container or well, so as to allow the 3D integrity of the injected mammalian skin biopsy to be maintained; b) incubating the injected mammalian skin biopsy deposited in step a) for at least 3 days in the presence of a second composition comprising an effective amount of a mixture comprising at least IL-1β, IL-23, and TGF-β for obtaining polarization of the T cells activated in step a) into LTh1 polarized T cells and/or LTh17 polarized T cells, and synthesis of inflammation markers, to form the ex vivo model of inflamed skin; c) contacting the ex vivo model of inflamed skin with a candidate compound, wherein the ex vivo model of inflamed skin comprises LTh1-polarized T cells and/or LTh17-polarized T cells; d) measuring an expression level of at least two inflammation markers of the model of inflamed skin; e) comparing the expression level of said at least two inflammation markers obtained in step d) with a control expression level; and f) identifying the anti-inflammatory efficacy of said candidate compound when the expression level of said at least two inflammation markers measured in step d) is lower than the control expression level, wherein said ex vivo model reflects more precisely and reproducibly the environment of inflamed skin as observed in vivo in a physiological context. Additionally, the embodiments in the dependent claims all overlap.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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