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 .
Detailed Action
This action is in response to the papers filed July 23, 2026.
Claim Amendments
Applicant’s amendment to the claims filed 07/23/2026 is acknowledged.
Claims 7-8, 10-12 and 26 have been cancelled.
Claims 5-6 are amended.
Claims 1-6, 9, 13-25, 27-28 are pending.
Claims 5, 14, 16-25, 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-4, 6, 9, 13 and 15 are under examination.
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.
Election/Restrictions
Applicant’s reply filed 07/23/2026 to the Requirement for Restriction/Election mailed 04/23/2026 is acknowledged. See also, attached interview summary.
Applicant elected without traverse:
Group 1, drawn to a method for determining whether an agent has an effect on a ciliated organoid having apical-out polarity.
Epithelial cell type: airway epithelial cell, wherein the airway epithelial cell is a normal human bronchial epithelial cell (NHBE).
Class of screening agents: a chemical or biological agent, wherein the chemical or biological agent is a cytotoxic reagent.
Determining characteristic: organoid motility.
Claims 5, 14, 16-25, 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/23/2026. Rejoinder of nonelected inventions will be reconsidered if a generic claim is finally held to be allowable.
Priority
The instant application 18/568,091 was filed on 12/07/2023. This application is a national stage of international application PCT/US2022/072815 filed 06/08/2022, claiming priority based on U.S. Provisional Applications Nos. 63/274,126 filed 11/01/2021, and 63/208,201 filed 06/08/2021.
Effective filing dates: Sufficient written support for the instantly claimed invention is not found in applicant’s priority documents. Accordingly, the instantly pending claims are found to have an effective filing date of 06/08/2022, based on the filing date of international application PCT/US2022/072815. If applicant believes sufficient written support for the invention as claimed is found in one or more priority documents, applicant may respond by particularly pointing out where support may be found by page and line number.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/09/2024 and 02/21/2025 have been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, or by applicant in an information disclosure statement (IDS), they have not been considered.
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 1-4, 6, 9, 13 and 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.
The preamble of claim 1 recites “[a] method for determining whether an agent has an effect on a ciliated organoid having apical-out polarity,” and the body of claim 1 recites a step of “contacting a ciliated organoid with an agent.” The claims are found to be indefinite because there is a lack of nexus between the preamble of claim 1 and the steps set forth in the body of claim 1. In particular, it is unclear whether “a ciliated organoid” in the contacting step should be considered the same “a ciliated organoid having an apical-out polarity” in the preamble. Therefore, it is unclear whether an apical-out polarity is a required limitation of the ciliated organoid recited in the contacting step.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend. Amending claim 1, line 3, to recite “the ciliated organoid” would be remedial.
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 1-4, 6, 9, 13 and 15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
The claim is directed to a process, which is a statutory category of invention.
With respect to the judicial exception, the claim is directed to an abstract idea in the form of a mental process, and thus directed to a judicial exception. Specifically, the claim recites a method for determining whether an agent has an effect on a ciliated organoid having apical-out polarity, the method comprising:
contacting a ciliated organoid with an agent,
comparing a characteristic of the organoid after the contacting with the same characteristic of the organoid before the contact, and
when the characteristic after the contacting has changed as compared to the characteristic before the contacting, determining that the agent has an effect on the organoid, or when the characteristic after the contacting has not changed as compared to the characteristic before the contacting, determining that the agent does not have an effect on the organoid.
Accordingly, the claimed invention is directed to a screening process for an agent, e.g., for a determining the effectiveness of a candidate drug, or for determining the toxicity of a potential pollutant or contaminant. The claimed invention particularly recites the mental processes performed by the practitioner of the screening, i.e., the practitioner is to compare the state of the organoid upon exposure to the agent to the state of a standard organoid, and then the practitioner is to determine (i) the agent has an effect on the organoid when the state of the organoid has changed relative to the standard or (ii) the agent has no effect on the organoid when the state of the organoid has not changed relative to the standard.
The claims are not found to recite additional elements that integrate the judicial exception into a practical application. The contacting step describes the necessary materials and preliminary steps required to perform the mental processes recited in the comparing and determining steps, i.e., an organoid must be obtained and exposed to the candidate agent before the mental processes based thereupon can be performed. Therefore, the contacting step amounts to insignificant pre-solution activity with respect to the judicial exception. To the extent that the claimed invention may be considered to implicitly include detection or measurement of the “characteristic” used to describe the state of the organoid relative to the standard, such a limitation would be directed to mere data gathering of the necessary information used as input to the mental processes in the comparing and determining steps.
The limitation of “a ciliated organoid having apical-out polarity” generally links use of the judicial exception to a particular technological environment. In this case, describing the organoid as a ciliated organoid having apical-out polarity fairly limits the practical use of the claimed invention to screening agents for their effect on the epithelial lining of internal organs or structures, e.g., the lungs, the airway passages, the fallopian tubes, the middle or inner ear, and the ependyma. However, at the time of filing, the making of ciliated organoids having apical-out polarity was well-understood, routine, conventional activity in the art. For example, Co et al. (2019) "Controlling epithelial polarity: a human enteroid model for host-pathogen interactions" Cell reports, 26(9), 2509-2520, describes a process of making a ciliated organoid having apical-out polarity and use of the organoid for modeling host-pathogen interactions. See, e.g., Abstract; Figures 1A-E. Sachs et al. (2019) “Long‐term expanding human airway organoids for disease modeling” The EMBO journal, 38: e100300, 20 pages, further describes an airway organoids (AO) and use of the organoids for disease modeling. See, e.g., Abstract, Figure 1. In one example, organoids were infected with a virus (RSV), and the motility of infected organoids was compared to the motility of uninfected organoids to determine the effects of viral exposure on the organoids. See, e.g., pages 5-6 and 15, and Figure 4.Accordingly, absent evidence to the contrary, the invention as claimed is not found to reflect a technological improvement or otherwise cover a particular solution to a technological problem.
In sum, the additional elements, considered individually or in combination, do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception itself. Rather, the intended purpose of the instantly claimed process is the positively recited mental processes found the final contacting and determining steps. Thus, based on the evidence of record, the invention as claimed is directed to patent eligible subject matter. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 9, 13 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Co et al. (2019) "Controlling epithelial polarity: a human enteroid model for host-pathogen interactions" Cell reports, 26(9), 2509-2520.
Co discloses a ciliated organoid having apical-out polarity (termed “enteroids”) and use of the organoid for modeling host-pathogen interactions. Enteroids were derived from duodenal tissue of mice or from small intestinal ileal tissue of humans, infected with pathogens, and the characteristics of infected organoids were compared to the same characteristics of uninfected organoids to determine the effects of pathogen exposure on the organoids. Pathogens were allowed to invade for 1 hour. See, e.g., Abstract, Figures 1A-E, Figures 6-7, and pages e2-e4. In another example, enteroids were treated with a cytotoxic reagent (EDTA), and the characteristics of treated organoids were compared to the same characteristics of untreated organoids to determine the effects of the cytotoxic reagent on the organoids. See, e.g., Figure 3.
Co further teaches accessing the apical surface is challenging because the apical surface is enclosed within the spheroid. Previous studies have employed microinjection techniques to introduce microbes and agents of interest into the spheroid lumens; however, such techniques are slow and labor-intensive and results can be confounded by the accessibility of the epithelial surface due to accumulation of mucus and cell debris within the enclosed organoid lumen. To overcome these challenges, Co teaches reversing the epithelial polarity such that the apical surface of the organoid faces outward, thereby making the apical surface accessible to experimental challenges. See, e.g., page 2510.
For these reasons, Co is found to anticipate the process as claimed in claims 1, 9, 13 and 15.
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 1-4, 6, 9, 13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Sachs et al. (2019) “Long‐term expanding human airway organoids for disease modeling” The EMBO journal, 38: e100300, 20 pages; in view of Co et al. (2019) "Controlling epithelial polarity: a human enteroid model for host-pathogen interactions" Cell reports, 26(9), 2509-2520.
Sachs discloses airway organoids (AO) and use of the organoids for disease modeling. Airway organoids were derived from human broncho-alveolar resections or lavage material and contain ciliated cells. See, e.g., Abstract, Figure 1. In one example, organoids derived from lung cancer patients were subjected to in vitro anti-cancer drug screening, wherein the characteristics of treated organoids was compared to the characteristics of untreated organoids to determine the effects of drug exposure on the organoids. Organoids were examined 5 days after drug exposure. See, e.g., pages 4-5 and 15, and Figure 3D. The anticancer drugs disclosed in Sachs are found to broadly read on the instantly recited “cytotoxic reagent” of dependent claim 13 as shown by the obtained IC50 values in Figure 3D. In another example, organoids were infected with a virus (RSV), and the motility of infected organoids was compared to the motility of uninfected organoids to determine the effects of viral exposure on the organoids. Organoids were examined 5 hours after viral exposure. See, e.g., pages 5-6 and 15, and Figure 4.
Organoids derived from human broncho-alveolar resections or lavage material, as described in Sachs, would be expected to contain normal human bronchial epithelial cells as well as additional cell types, including stromal cells, vascular endothelial cells and/or immune cells, as claimed in claims 3-4, because the cellular composition of the organoids would be derived from that of the in vivo source material, in contrast to alternative de novo processes of constructing organoids, e.g., from induced-pluripotent stem cells. "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968).
The difference between the instantly claimed invention and that of Sachs is the limitation of an organoid having an “apical-out polarity,” as claimed in the preamble of claim 1.
The teachings of Co have been provided above and hereby incorporated by reference.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the organoids of Sachs to have an apical-out polarity, in view of Co, with a reasonable expectation of success because reversing the epithelial polarity such that the apical surface of the organoid faces outward would make the apical surface more accessible to experimental challenges. See, e.g., page 2510 of Co.
For these reasons, the invention as claimed in claims 1-4, 6, 9, 13 and 15 would have been prima facie obvious over the prior art.
Claims 1-4, 6, 9, 13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over US20170275592A1 to Sachs et al; in view of Co et al. (2019) "Controlling epithelial polarity: a human enteroid model for host-pathogen interactions" Cell reports, 26(9), 2509-2520.
Sachs discloses epithelial organoids, e.g., lung organoids, and use of the organoids for drug discovery screening, toxicity assays, infectious disease modeling and studies of pathogenetic mechanisms. See, e.g., Abstract; par. 5-25, 491, 541-544. The organoids are representative of the proximal lung epithelium, contain ciliated cells, and are thought to faithfully represent the in vivo situation. See, e.g., par. 466-467, 485. In working examples, organoids were derived from lung and/or trachea resections of human subjects, and organoids were found to contain cells having epithelia and mesenchymal phenotypes. See, e.g., Figure 25, and par. 589, 636-638.
Organoids derived from human lung and/or trachea resections, as described in Sachs, would be expected to contain normal human bronchial epithelial cells or tracheal epithelial cells as well as additional cell types, including stromal cells, vascular endothelial cells and/or immune cells, as claimed in claims 3-4, because the cellular composition of the organoids would be derived from that of the in vivo source material, in contrast to alternative de novo processes of constructing organoids, e.g., from induced-pluripotent stem cells. "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968).
In some embodiments, Sachs discloses a process of studying the effectiveness or toxicity of a drug, the method comprising: stimulating a normal, infected or diseased organoid with the drug, measuring a change in the characteristics of the organoids, e.g., organoid motility, and correlating the change with drug efficacy. Drugs are evaluated for their ability to modify, kill and/or treat a patient’s cells, or drugs are evaluated for toxicity rather than therapeutic effects. See, e.g., par. 26-33, 492-517, 545, 555-562, 573-575. In a working example, lung organoids were infected with a virus (RSV) and changes in organoid motility was measured, demonstrating the model may be used to test the efficacy of antiviral drugs. See, e.g., par. 643.
The difference between the instantly claimed invention and that of Sachs is the limitation of an organoid having an “apical-out polarity,” as claimed in the preamble of claim 1.
The teachings of Co have been provided above and hereby incorporated by reference.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the organoids of Sachs to have an apical-out polarity, in view of Co, with a reasonable expectation of success because reversing the epithelial polarity such that the apical surface of the organoid faces outward would make the apical surface more accessible to experimental challenges. See, e.g., page 2510 of Co.
For these reasons, the invention as claimed in claims 1-4, 6, 9, 13 and 15 would have been prima facie obvious over the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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