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 .
Applicant cancels claims 3 and 11-12. Claims 1-2, 4-10 and 13-22 are currently pending. Claims 18-19 and 21-22 remain withdrawn as being drawn to a nonelected group. Claims 1-2, 4-10, 13-17 and 20 are under examination. Any objection or rejection of record in the previous
Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s
amendments and/or arguments. This action is Final.
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 1-2, 4-10, 13-17 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions (i.e., product of nature, a law of nature, a natural phenomenon, or an abstract idea) without significantly more. This rejection is maintained and modified as necessitated by amendments.
Every claimed invention must be examined to determine whether the claimed invention complies with 35 U.S.C. 101, particularly whether the claimed invention falls within a 35 U.S.C. 101 judicial exception of non-patentable subject matter (e.g., an abstract idea, law of nature, natural phenomenon, natural product etc.). Phenomena of nature, though just discovered, natural products, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work. See MPEP 2106. As per the “2019 Revised Subject Matter Eligibility Guidance” (Federal Register Vol. 84, No. 4, available 01-07-2019), claims drawn to a process, machine, manufacture or composition of matter are further analyzed according to a two-part process to determine if A) the claim(s) is/are “directed to” a judicial exception because the claims(s) recite(s) a judicial exception (i.e. prong one) that is not integrated into a practical application (i.e. prong two) and, if so, if B) the claim(s) provide(s) an inventive concept, i.e. recite(s) additional elements that amount to significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES
Claims 1-2, 4-10, 13-17 and 20 are directed to one of the statutory classes. Claims 1-2, 4-10, 13-17 and 20 are directed to a method for characterizing a physiological effect of a composition comprising two or more active drug compounds (Process).
Step 2A, Prong One — Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES
Claims 1-2, 4-10, 13-17 and 20 recite the abstract idea of receiving and processing data using mental steps. Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection (see MPEP 2106.04). Abstract ideas include certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, determining, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include:
• Characterizing a physiological effect of a composition comprising two or more active drug compounds (mental process, human is capable of receiving/ collecting data, observing/evaluating, organizing information; claims 1-2, 4-10, 13-17 and 20).
• A composition validation screen (CVS), in which screen 3D microtissue derived from a primary patient sample is exposed to the composition of step b), so as to characterize a physiological effect of said composition on the 3D microtissue (mental process, human is capable of receiving/ collecting data, observing/evaluating, organizing information; claims 1-2, 4-10, 13-17 and 20).
• One parameter representing the characterized physiological step is determined (mental process, human is capable of receiving/ collecting data, observing/evaluating/determining, organizing information; claims 1-2, 4-10, 13-17 and 20).
• Range finding step (mental process, human is capable of receiving/ collecting data, observing/evaluating, organizing information; 1-2, 4-10, 13-17 and 20).
• Obtaining a molecular profile (mental process, human is capable of receiving/ collecting data, observing/evaluating, organizing information; claims 4-5 and 16-17).
• Using the molecular profile to detect genetic aberrations, mRNA or protein expression level (mental process, human is capable of receiving/ collecting data, observing/evaluating, organizing information; claim 5).
• Using the molecular profile to correlate at least one parameter which characterizes the physiological effect as obtained in the composition selection screen (CSS) or the composition validation screen (CVS) of said 3D microtissue (mental process, human is capable of receiving/ collecting data, comparing date, observing/evaluating, organizing information; claims 16 and 17).
Therefore, the claims recite elements that constitute one or more judicial exceptions
Step 2A, Prong Two — Does the Claim Recite an Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. However, absent are any additional elements recited in the claim beyond the judicial exceptions which integrate the exception into a practical application of the exception. The “integration into a practical application” requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
The claim analysis continues with identifying additional elements beyond the judicial exceptions that might evidence integration of the judicial exceptions into a practical application. The steps or elements in addition to the judicial exceptions are: “a composition selection screen (CSS), in which screen a 3D microtissue derived from one or more cell lines is exposed to said composition comprising two or more active drug compounds”, “3D microtissues derived from one or more cell lines are exposed to different concentrations of each compound of the composition and then removing the compound”, “feeding the dataset into a database” “application of a defined bolus”, which is not indicative of integration into practical application. These steps, recited at a high level of generality, comprise routine data gathering, which is considered an insignificant extra-solution activity. This data gathering is required for using the judicial exceptions. (See MPEP 2106.05(g)). There are no further/additional steps which applies either the identified judicial exception into practical application. Thus, a careful evaluation of the claims as a whole fails to reveal the practical application of the judicial exception to, e.g., effect an improvement to the functioning of a computer or other technology/technical field, effect a particular treatment or prophylaxis for a disease or medical treatment, implement a particular machine that is integral to the claim, or effect a transformation or reduction of a particular article to a different state or thing, or to apply the judicial exception in another meaningful way beyond generally linking its use to a particular technological environment. Accordingly, the claims do not integrate the judicial exception(s) into a practical application and is therefore directed to a judicial exception.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to “significantly more” than the judicial exception(s) itself. The claims as a whole are analyzed to determine whether any additional element/step, or combination of additional elements/steps, in addition to the identified judicial exception(s) is sufficient to ensure that the claim amounts to “significantly more” than the exception(s).
The eligibility analysis proceeds with identifying any additional elements or limitations, separate from the judicial exceptions, that might potentially render the claims directed to a judicial exception patent eligible. To render the claims patent- eligible, these elements must comprise meaningful limitations that add to or transform the judicial exception to the effect that it amounts to significantly more than the natural correlation or abstract idea itself - i.e. provide an “inventive concept’. The elements that are in addition to the judicial exception comprise: a composition selection screen (CSS), in which screen a 3D microtissue derived from one or more cell lines is exposed to said composition comprising two or more active drug compounds, a 3D microtissues derived from one or more cell lines are exposed to different concentrations of each compound of the composition and then removing the compound, application of a defined bolus and feeding the dataset into a database. When considered separately and in combination, these elements do not add significantly more to the judicial exception. These steps are well-understood, routine and conventional activities in the field. For example, Sundaram et al. (U.S. Patent Application Publication US 2014/022246 A1, published August 14, 2014), cited on the IDS filed January 29, 2025, discloses a composition selection screen (CSS), in which screen a 3D microtissue derived from one or more cell lines is exposed to said composition comprising two or more active drug compounds, a 3D microtissues derived from one or more cell lines are exposed to different concentrations of each compound of the composition and then removing the compound, and feeding the dataset into a database. Additionally, Kelm et al. (United States Patent Application Publication US 2018/0252703 A1, published September 06, 2018, effectively filed August 22, 2016) and Domenyuk et al. (U.S. Patent Application Publication US 2019/0078093 A1, published March 14, 2019, effectively filed March 18, 2017, disclose use of application by a defined bolus.
The claims recite an abstract idea with additional elements. Because these elements are not inventive concepts, the claims do not integrate the abstract idea into a practical application. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Accordingly, the claims do not qualify as patent-eligible subject matter.
For further information, please see the latest revision of MPEP 2104-2106 {Patent Subject Matter Eligibility Under 35 U.S.C. 101}, including MPEP 2106.04 {Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception} and 2106.05 {Eligibility Step 2B: Whether a Claim Amounts to Significantly More}, as well as the guidance on Subject Matter Eligibility, including the 2019 Guidance issued Jan. 7, 2019, and the October 2019 Update, provided on the USPTO website at https:/Awww.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter- eligibility.
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 1-2, 4-10, 13-17 and 20 are rejects under 35 U.S.C. 103 as being as being unpatentable over Vinci et al. (“Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation”, BMC Biol 10, 29, published March 22, 2012, in view of Domenyuk et al. (U.S. Patent Application Publication US 2019/0078093 A1, published March 14, 2019, effectively filed March 18, 2017). This is a new rejection as necessitated by amendments.
Regarding claim 1, Vinci teaches a method for characterizing a physiological effect of a composition comprising two or more active drug compounds (Page 2, Right Column, Last Two Paragraph, Page 10, Left Column, Last Paragraph, Figure 1 and Table 2). Vinci teaches a range finding step (RFS), in which step a plurality of 3D microtissues derived from one or more cell lines are exposed to different concentrations of each active drug compound of the composition, so as to determine suitable concentration ranges of the active drug compounds (Table 2 and Figures 7 and 8). Vinci teaches the 3D microtissue is exposed to each active drug compound one or more times (Table 2). Vinci teaches a composition selection screen (CSS), in which screen a 3D microtissue derived from one or more cell lines is exposed to said composition comprising two or more active drug compounds (Abstract, Page 2, Right Column Second Paragraph and Table 2). Vinci teaches a composition validation screen (CVS), in which screen 3D microtissue derived from a primary patient sample is exposed to the composition of step b), so as to characterize a physiological effect of said composition on the 3D microtissue (Abstract, Page 2, Right Column, Second-Fourth Paragraph, Page 10, Left Column, Last Two Paragraphs and Tables 1 and 2).
Regarding claim 2, Vinci teaches at least one parameter representing the characterized physiological effect is generated or determined in the method (i.e., cell viability/size, volume etc., Page 10, Left Column, Third Paragraph—Right column, Last Paragraph, Table 2 and Figure 1).
Regarding claim 4, Vinci teaches a step of obtaining a molecular profile of at least one of the 3D microtissues derived from one or more cell lines, and the 3D microtissues derived from a primary patient sample (Page 4, Right Column, Second Paragraph, Page 14, Right Column, First Paragraph, Page 17, Left Column, First Paragraph and Right Column, First Paragraph, Page 10, Right Column, First Paragraph, Figure 3 and Table 1).
Regarding claim 5, Vinci teaches the step of molecular profiling is used to detect genomic aberrations, and/or mRNA or protein expression levels (Page 14, Right Column, First Paragraph, Page 17, Left Column, First Paragraph and Right Column, First Paragraph, Page 10, Right Column, First Paragraph, Figure 3 and Table 1).
Regarding claim 6, Vinci teaches the parameter representing the characterized physiological effect is determined over time in at least one of step a), b) and/or c)(Page 10, Right column, Last Paragraph and Figures 1-6).
Regarding claim 7, Vinci teaches the parameter representing the characterized physiological effect is the size of the 3D microtissue (Page 2, Right Column, Last Two Paragraphs, Page 4, Left Column, Second Paragraph, Page 10, Left Column, Last Two Paragraphs, Page 16, Left Column, Third Paragraph and Figures 1 and 8).
Regarding claim 8, Vinci teaches the size is actual size, relative size and/or relative size change over time is determined in at least one of step a), b) and/or c) (Page 2, Right Column, Last Two Paragraphs, Page 4, Left Column, Second Paragraph, Page 10, Left Column, Last Two Paragraphs, Page 16, Left Column, Third Paragraph and Figures 1 and 8).
Regarding claim 9, Vinci teaches the size determination of the 3D microtissue refers to at least one parameter consisting of diameter, perimeter and volume (Page 2, Right Column, Last Two Paragraphs, Page 4, Left Column, Second Paragraph, Page 10, Left Column, Last Two Paragraphs, Page 16, Left Column, Third Paragraph and Figures 1 and 8).
Regarding claim 10, Vinci teaches the size is determined in at least one of step a), b) and/or c) over a period of >1 and <20 days (Page 2, Right Column, Last Two Paragraphs, Page 4, Left Column, First-Second Paragraphs and Figures 1-3).
Regarding claim 13, Vinci teaches the composition comprising two or more active drug compounds is removed after the microtissue was exposed thereto for a given period of time (Page 16, Left Column, Last Paragraph).
Regarding claim 14, Vinci teaches a step of composition toxicity testing is provided, in which step a microtissue representing connective tissue is exposed to the composition of step b) (Page 10, Right Column, Fourth Paragraph—Right Column, First Paragraph).
Regarding claim 15, Vinci teaches at least one 3D microtissue has been produced in a hanging drop culture system or a low adhesion well culture system (Page 2, Left Column, Third Paragraph and Right Column, Last Paragraph and Page 12, Right Column, Third Paragraph).
Regarding claim 16, Vinci teaches the molecular profile of at least one 3D microtissue is correlated with at least one parameter which characterizes the physiological effect as obtained in the composition selection screen (CSS) or the composition validation screen (CVS) of said 3D microtissue (Page 10, Left Column, Last Two Paragraph, Page 17, Right Column, Last Paragraph).
Regarding claim 17, Vinci teaches creating or feeding a database with datasets (Page 12, Left Column, Second Paragraph, Page 14, Left Column, Second Paragraph and Page 16, Right Column, First Paragraph). Vinci teaches at least one molecular profile of at least one 3D microtissue (Page 4, Right Column, Second Paragraph, Page 14, Right Column, First Paragraph, Page 17, Left Column, First Paragraph and Right Column, First Paragraph, Page 10, Right Column, First Paragraph and Figure 3). Vinci teaches at least one parameter which characterizes the physiological effect as obtained in the composition selection screen (CSS) or the composition validation screen (CVS) of said 3D microtissue Page 10, Left Column, Third Paragraph—Right column, Last Paragraph, Table 2 and Figures 1-7).
Regarding claim 20, Vinci teaches composing the compositions comprising two or more active drug compounds (Page 17, Right Column, Last Paragraph).
Vinci does not explicitly teach or suggest exposing the 3D microtissue is exposed to each active drug compound by application of a defined bolus.
Domenyuk teaches predicting and monitoring a drug response invitro (Page 1, [0009], Page 9, [0087] and [0091] and Page 17, [0128]-[0129]). Domenyuk teaches administering more than one active drug (Page 7, [0056], Page 36, [0224], Pages 71-72, [0508], Page 38-39, [0243], Page 42, [0262] and [0272], Page 46, [0324], Pages 99-100, [1063], Page 116, [1082] and Page 119, [1141]). Domenyuk teaches using three-dimensional structures (Page 33, [0197]). Domenyuk teaches obtaining a molecular profile (Pages 12-13, [0110] and Page 116, [1082]). Domenyuk teaches characterizing a physiological effect of a composition on a tissue (Page 9, [0089]-[0091], Page 26, [0146] and Page 36, [0222]). Domenyuk teaches at least one parameter representing the characterized physiological effect is generated or determined in the method (Pages 12-13, [0110], Page 29, [0170]-[0171], Page 30, [0177] and Table 2). Domenyuk teaches a composition validation screening and composition selection screen (Page 18, [0132], Page 115-116, [1080] Page 1, [0008], Page 51, [0368]-[0369] and Page 52, [0374]-[0376]). Domenyuk teaches a toxicity screening (Page 36, [0231], Page 37, [0239] and Page 72, [0516]). Domenyuk teaches administering the active drug to the tissue by application of a defined bolus (Page 74, [0547] and Pages 47-48, [0338]). Domenyuk teaches using the customized arrays disclosed within allows for detecting biomarkers/biosignatures that lead to improved cross-validated error rates in multivariate prediction models (Page 26, [0146]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Vinci, with the teachings of Domenyuck to expose the 3D microtissue to the active drug compounds by application of defined bolus. This would allow for detecting biomarkers/biosignatures that lead to improved cross-validated error rates in multivariate prediction models as taught by Domenyuck (Page 26, [0146]).
Additional Relevant Prior Art
Kelm et al. (United States Patent Application Publication US 2018/0252703 A1, published September 06, 2018, effectively filed August 22, 2016)
Kelm is relevant to instant claims in that Kelm discloses dose (bolus) dependent size determination of 3D microtissues being treated with at least 3 active drug compounds as well as using a range finding step (Page 7, [0181] and Page 5, [0122]-[0131]).
Response to Arguments
Applicant’s argument and amendments filed October 10, 2025, with respect to the rejections under 35 U.S.C. § 102 and 35 U.S.C. 112b have been fully considered and are persuasive. Therefore, these rejections have been withdrawn.
However, upon further consideration, new grounds of rejections under 35 U.S.C. § 103 are made in view of Applicant’s amendments to claims. As discussed above, newly cited Vinci and Domenyuck disclose an in vitro method for characterizing a physiological effect of a composition comprising two or more active drug compounds, the method comprising a range finding step, in which step a plurality of 3D microtissues derived from one or more cell lines are exposed to different concentrations of each active drug compound of the composition, so as to determine suitable concentration ranges of the active drug compounds, and the 3D microtissue is exposed to each active drug compound at least one or more time, by application of a defined bolus.
Applicant’s arguments and amendments filed October 10, 2025, with respect to the
rejections under U.S.C. § 101 have been fully considered but are not deemed to be persuasive.
As discussed above adding the range finding step as well as application of a defined bolus does not add something more to the judicial exception in that it does not describe how it solves the particular problem, but merely describes limitations for finding a suitable concentration as well as how to apply the active drug compounds, which are routine data gathering techniques, to characterize the physiological effect. Applicant asserts that the instant invention may also be used in the treatment of cancer by application of the defined bolus as well as providing advantageous anti-cancer effects, as disclosed in the specification. It is not proper to import claim limitations from the specification or outside knowledge into the claims. “Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the language is broader than the embodiment.” Superguide Corp. v. Direc TV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004). While the specification may disclose the instant invention being used in the treatment of cancer by application of the defined bolus and providing advantageous anti-cancer effects, these limitations are not recited in the instant claims. Therefore this rejection is maintained as set forth above.
Therefore, for all these reasons, and those listed above, Vinci in view of Domenyuck are deemed to render the instant invention obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684