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 27, 2023.
Claim Listing
The instantly pending claims are the original claims filed 07/27/2023.
Claims 1-19 are pending and under examination.
Priority
The instant application 18/359,916 was filed on 07/27/2023. This application claims priority based on U.S. Provisional Application 63/395,316 filed 08/04/2022.
Effective filing dates:
The following limitations are found to lack sufficient written support in applicant’s priority application, U.S. Provisional Application 63/395,316:
the spherical structure has an average diameter between 20 μm and 100 μm (claim 3);
the enzyme comprises an animal origin-free, recombinant enzyme (claim 6);
the cells are differentiated for at least 8 days (claim 16); and
the ciliated cells are increased by 24-fold in the two-dimensional human nasopharyngeal organoids when compared with that in the one or more three-dimensional human nasopharyngeal organoids (claim 18).
For these reasons, claims 3, 6, 16 and 18 are not found to benefit from the earlier filing date of U.S. Provisional Application 63/395,316. If applicant believes that one or more of said limitations are sufficiently supported by the priority application, applicant may respond by identifying specifically where written support may be found.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/07/2025 and 11/10/2025 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 Objections
Claims 7-9 and 15 are objected to because of the following informalities:
In claim 7, the term p63a+ should be p63α+ instead.
In claim 8-9, the phrase respiratory proximal epithelial cell types should be proximal respiratory epithelial cell types instead.
In claim 15, the phrase one or more three-dimensional human nasopharyngeal organoids should be the one or more three-dimensional human nasopharyngeal organoids instead.
Appropriate action 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.
Claim 7 is 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 7 recites that the nasopharyngeal organoids are “rich” in p63α+ epithelial cells, SCGB1A1/CC10+ secretary club cells, acetyl-α-Tubulin+ ciliated cells and MUC5AC+ mucus secretary goblet cells. The term “rich” is a relative term which renders the claim indefinite. The term “rich” is not defined by the claim, and the specification does not provide a standard for ascertaining the requisite degree. For example, one of ordinary skill in the art would not have been reasonably apprised of the number and/or density of each cell type is required to meet the “rich” limitation. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 7-13, 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rajan et al. (15 Feb 2022) “The human nose organoid respiratory virus model: an ex vivo human challenge model to study respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapeutics” MBio, 13(1), e03511-21.
Rajan discloses a non-invasive method for generating human three-dimensional nasopharyngeal organoids (human nose organoids, HNOs), comprising:
non-invasively collecting nasopharyngeal swab samples;
culturing the nasopharyngeal swab samples in a matrix containing one or more niche factors for stimulating the three-dimensional nasopharyngeal organoids growth; and
obtaining one or more three-dimensional human nasopharyngeal organoids after culturing the nasopharyngeal swab samples in the matrix for 14-21 days.
See, e.g., Abstract; pages 2-3, and 11; and Figure 1. Figure 1A reproduced, below:
PNG
media_image1.png
261
1033
media_image1.png
Greyscale
Therefore, Rajan anticipates the method according to claim 1.
Claim 11 further recites a step of dissociating the one or more three-dimensional human nasopharyngeal organoids into a single cell suspension for the creation of one or more human two- dimensional nasopharyngeal organoid. This additional step is also disclosed by Rajan, i.e., in generating air-liquid interface (ALI) cultures. See, e.g., Abstract; pages 2-3, and 11; and Figure 1.
Regarding dependent claim 2, Rajan teaches the three-dimensional nasopharyngeal organoids
comprise a spherical structure. See, e.g., Figures 1A to C.
Regarding dependent claim 3, the claim recites that ten spherical structure has an average diameter between 20 μm and 100 μm. Figure 1C shows that Rajan’s organoids have a diameter of about 70 μm, based on the provided scale bar.
Regarding dependent claims 4 and 12, Rajan teaches the niche factors comprise fibroblast growth factor (FGF), R-Spondin 1 and Noggin. See, airway organoid (AO) media recipe in Supplementary Table 1 (attached).
Regarding dependent claims 5 and 13, Rajan teaches the one or more three-dimensional human nasopharyngeal organoids cultured on day 14 are passaged using an enzyme (trypsin) and/or mechanical shearing. See, e.g., Abstract; pages 2-3, and 11; and Figure 1.
Regarding claims 7-9, 17-18, Rajan discloses that the differentiated cell population contained KRT5-positive basal cells, SCGB1A1/CC10-postive secretory club cells, MUC5AC-postive goblet cells, and acetylated alpha tubulin-positive ciliated cells. See, e.g., pages 2-3, 12; and Figures 1E to G.
Accordingly, Rajan expressly discloses the limitations of dependent claims 8-9 and 17.
Rajan does not expressly disclose (1) the organoids contain p63α+ epithelial cells, as claimed in claim 7, or (2) the ciliated cells are increased by 24-fold in the two-dimensional human nasopharyngeal organoids when compared with that in the one or more three-dimensional human nasopharyngeal organoids, as claimed in claim 18.
A recitation of an intended result or functional property of the claimed process must result in a manipulative difference between the claimed invention and the cited prior art in order to patentably distinguish the claimed invention from the cited prior art. If the prior art process is capable of achieving the intended result recitation, or if the functional property naturally flows from performing the process of the prior art, then the cited prior art reads on the intended result or functional property recitation. There is no requirement that the cited prior art expressly teach or suggest the intended result or functional property recitation. See MPEP 2111.04 (Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure).
In this case, the recitations (1) and (2) describe an intended result or functional property that naturally flows from performing the process steps positively recited in the claims. The recitations (1) and (2) do not clearly limit the claimed process to a particular manipulative action that patentably distinguishes the claimed invention from that of the cited prior art. Rather, as outlined above, the manipulative actions positively recited by the claims, i.e., the process steps of claims 1 and 11, are taught by the cited prior art (Rajan). Accordingly, the prior art process would have been capable of achieving the claimed intended results, and/or the claimed functional properties would have naturally flowed from performing the prior art process, and thus the prior art process reads on the intended result or functional property recitations. For these reasons, recitations (1) and (2) are not found to patentably distinguish the claimed invention from the cited prior art.
Regarding dependent claims 10 and 18, the claims recite that the three-dimensional (claim 10) or two-dimensional (claim 18) nasopharyngeal organoids serve as useful tools to study the transmission, tropism, and innate host responses of emerging respiratory viruses comprising influenza virus (claim 10) or coronavirus (claim 19), which help to evaluate the pathophysiological characteristics of the emerging respiratory viruses.
Purpose or intended use recitations must result in a structural or manipulative difference to patentably distinguish the claimed invention from that of the prior art. If the product made by the prior art process is capable of performing the intended use recited by the claims, then the prior art satisfies the intended use limitation. See, e.g., In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963); In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962); In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997). See MPEP 2111.02.
In this case, as outlined above, the processes of making and the products made (three- and two-dimensional organoids), as found in the cited prior art (Rajan), are found to be structurally or manipulatively the same as those of the invention as claimed. No structural or manipulative difference is found to clearly and patentably distinguish the claimed invention from that of the prior art. Moreover, similar to the recited intended use, Rajan acknowledges that airway organoids (AO) are known as robust models of respiratory viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus (pg. 9), and Rajan’s organoids were used to study infection of respiratory syncytial virus (RSV) and SARS-CoV-2. See, e.g., Abstract; page 9; and Figures 2-5. Accordingly, since Rajan’s organoids are capable of performing the recited purpose or intended use, as claimed in claims 10 and 19, the prior art satisfies the purpose pr intended use limitation.
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 6, 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Rajan et al. (15 Feb 2022) “The human nose organoid respiratory virus model: an ex vivo human challenge model to study respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapeutics” MBio, 13(1), e03511-21, as applied to claims 1-5, 7-13, 17-19 above.
Regarding dependent claims 6 and 14, the claims recite the enzyme comprises an animal origin-free, recombinant enzyme.
Rajan teaches the enzyme is trypsin. See, e.g., page 11. However, Rajan does not expressly teach that the trypsin is a recombinant, animal-origin free trypsin.
Recombinant, animal-origin free trypsin was known in the art prior to the effective filing date of the instantly claimed invention. One of ordinary skill in the art would have understood recombinant, animal-origin free trypsin to be a suitable alternative to animal-derived trypsin for passaging cells while reducing the risk of contamination. Official Notice taken, if necessary.
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 process of Rajan by using a recombinant, animal-origin free trypsin (enzyme), as known in the art, with a reasonable expectation of success because recombinant, animal-origin free trypsin to be a suitable alternative to animal-derived trypsin for passaging cells while reducing the risk of contamination.
Regarding dependent claim 15, the claim recites the one or more three-dimensional human nasopharyngeal organoids dissociated into a single cell suspension is further seeded in an insert pre-coated with rat tail collagen I until reaching a confluent monolayer.
Rajan teaches the one or more three-dimensional human nasopharyngeal organoids dissociated into a single cell suspension is further seeded in an insert pre-coated with bovine collagen I until reaching a confluent monolayer. See, e.g., page 11.
Accordingly, the difference is that the claims recite rat tail type I collagen; whereas, Rajan teaches bovine type I collagen.
Rat tail type I collagen was known in the art prior to the effective filing date of the instantly claimed invention. One of ordinary skill in the art would have understood rat tail type I collagen to be a suitable alternative to bovine type I collagen for culturing cells. Official Notice taken, if necessary.
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 substitute bovine type I collagen, as found in Rajan, with rat tail type I collagen, as known in the art, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding dependent claim 16, Rajan teaches that a single cell suspension was seeded in a pre-coated insert, and then, after 4 days, confluent monolayers were cultured using differentiation medium until 21 days. See, e.g., page 11.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMES JOSEPH GRABER/Examiner, Art Unit 1631