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 June 22, 2026.
Claim Amendments
Applicant’s amendment to the claims filed 06/22/2026 is acknowledged.
Claims 12-14 have been cancelled.
Claims 20-23 are newly added.
Claims 1-2, 4, 7-11, 15-19 are amended.
Claims 1-11, 15-23 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.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 02/24/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. Applicant’s remarks filed on 06/22/2026 have been carefully considered but are found to be moot or otherwise obviated by the new grounds of rejection in this action.
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 21 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.
This rejection is newly applied, necessitated by amendment.
Claim 21 recites a “hockey-shaped brush.” The limitation is found to be indefinite because the term “hockey” does not describe a shape. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 21 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly applied, necessitated by amendment.
Claim 21 recites a “hockey-shaped brush.” The limitation is new matter because the disclosure as originally filed does not describe a brush having a “hockey” shape. Paragraph 26 of the specification describes a “specially designed brush,” and Figure 1 appears to depict a modified oropharyngeal swab having an angled segment towards the sampling end such that the modified swab reaches the nasopharynx of a human subject when inserted into the oral cavity. Compare to, Matti et al. (2021) “An alternative way to perform diagnostic nasopharyngeal swab for SARS-CoV-2 infection” American Journal of Otolaryngology, 42(2), 102828, 4 pages. The original disclosure neither describes a “hockey-shaped brush,” as instantly claimed, nor brushes having the shapes of hockey-related objects, e.g., hockey sticks. For these reasons, claim 21 includes new matter.
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 1-3, 5-11, 17-19 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over CN 114149958 A to Li et al., published 2022-03-08.
This rejection is newly applied, necessitated by amendment.
CN 114149958 A to Li et al. was published in a non-English language. This rejection relies on a machine translation generated by Espacenet.com, and a copy of said machine translation has been provided with this action.
Li discloses methods of culturing nasal mucosa organoids from nasopharyngeal swabs, the method comprising non-invasively collecting nasopharyngeal swab samples from a nasopharynx of a human subject, culturing the nasopharyngeal swab samples in a matrix (Matrigel®) containing one or more niche factors for stimulating three-dimensional nasopharyngeal organoids growth, and obtaining one or more three-dimensional human nasopharyngeal organoid after culturing the nasopharyngeal swab samples in the matrix for 6-12 days. See, Abstract, and pages 1-2 of the translation. See also, Example 1 on pages 3-4.
Accordingly, the difference between the invention as claimed in claim 1 and that of Li is the numerical range of days the cell culture is performed.
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In this case, claim 1 recites that the cell culture is performed for 14-21 days, and Li discloses performing the cell culture for 6-12 days. However, one of ordinary skill in the art would have recognized that the culturing time is a result-effective variable effecting cellular growth and differentiation, and the optimal culturing time depends on the culturing conditions as a whole, including, e.g., temperature, gas overlay, pH level and biologically-active media components. Further, Li discloses that the organoids grow rapidly and can be “stably cultured for a long time” (Abstract). Therefore, one of ordinary skill in the art would have been led to optimize the culturing time through routine experimentation. For these reasons, absent a secondary consideration, the claimed range of 14-21 days for cell culture would have been prima facie obvious over the prior art.
Accordingly, the invention as claimed in claim 1 would have been prima facie obvious over the prior art.
Regarding dependent claim 2, the organoids have a spherical structure. See, Examples 1-11 on pages 4-6, and Figures 1-11.
Regarding dependent claim 3, the organoids are digested to a uniform diameter of about 20-30 µm for passaging. See, Examples 5 and 9 on page 5.
Regarding dependent claim 5, the organoids are passaged using an enzyme (TrypLE™). See, Examples 5 and 9 on page 5. The differences in culturing time has been addressed above with respect to claim 1.
Regarding dependent claim 6, the enzyme is an animal origin-free, recombinant enzyme (TrypLE™). See, Example 5 on page 5.
Regarding dependent claim 11, Li discloses a step of dissociating the one or more three-dimensional human nasopharyngeal organoids into a single cell suspension during passaging. See, Example 5 and 9 on page 5. The claim language “for creating one or more two-dimensional human nasopharyngeal organoids” describes a purpose or intended use of the obtained cell suspension without necessarily resulting in a structural or manipulative difference that patentably distinguishes the claimed invention from that of the prior art. Rather, since Li’s suspension would have been capable of creating one or more two-dimensional human nasopharyngeal organoids, the purpose or intended use limitation is met by the prior art. See, MPEP 2111.02. Claims 17-19, reciting characteristics or properties of the “two-dimensional human nasopharyngeal organoids” of claim 11, are included in the basis of this rejection because, as discussed above, creation of the two-dimensional human nasopharyngeal organoids is only described as a purpose or intended use of the obtained suspension, and no step of creating one or more two-dimensional human nasopharyngeal organoids is positively recited in claims 11, 17-18.
The claims further recite the organoids comprise p63α+ epithelial cells, SCGB1A1/CC10+ secretory club cells, acetyl-α-Tubulin+ ciliated cells and MUC5AC+ mucus secretory goblet cells (claim 7); the organoids contain four proximal respiratory epithelial cell types (claims 8), wherein the proximal epithelial cell types are basal cells, club cells, ciliated cells and goblet cells (claim 9); and the organoids comprise sialic acid receptors (claim 22), wherein the sialic acid receptors comprise human and avian sialic acid receptors (claim 23).
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). See, MPEP 2112.
In this case, the limitations of claims 7-9, 17-18 and 22-23, describing the epithelial cell types and phenotypic traits of the organoids as obtained from the nasopharynx of a human subject, are directed to an intended result or functional property of performing the process steps (manipulative actions) positively recited in claim 1. A recitation of an intended result or functional property of the claimed process must result in a manipulative difference between the claimed process and the cited prior art in order to patentably distinguish the claimed process from the cited prior art. If the prior art process is capable of performing the intended result, or if the functional property naturally flows from the prior art process, then the 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, but only that the subject matter is, in fact, present in the cited prior art. As outlined above, the manipulative actions positively recited by the claims would have been prima facie obvious over the cited prior art. In particular, Li obtains the organoids by non-invasively collecting nasopharyngeal swab samples from a nasopharynx of a human subject, as claimed, and, therefore, the intended result or functional property limitations of claims 7-9, 17-18 and 22-23, describing the epithelial cell types and phenotypic traits of the organoids as obtained from the nasopharynx of a human subject, would have naturally flowed from performing the process steps taught by Li. Moreover, Li recognizes that the organoids contain a variety of cellular components, including ciliated cells, secretory cells, basal cells and goblet cells, and the tissue characteristics of epithelial cells are well reserved in vitro. See, Abstract, and page 1 of the translation. Accordingly, absent evidence to the contrary, the intended result or functional property recitations are not found to patentably distinguish the claimed invention from the cited prior art.
Regarding dependent claim 10, the claim recites that the three-dimensional nasopharyngeal organoids are usable as tools to study transmission, tropism, and innate host responses of emerging respiratory viruses comprising influenza virus, 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, the purpose or intended use recitations are not found to necessarily result in a structural or manipulative difference that patentably distinguishes the claimed invention from that of the prior art. Rather, the claimed process of making the organoids would have been prima facie obvious over the prior art, and, consequently, the products made would have been capable of performing the recited purpose or intended use. Moreover, Li recognizes that the organoids provide an ideal model for studying the mutation, infection and spread of coronaviruses, immune mechanisms and development of antiviral drugs and vaccines. See, page 7 of the translation. For these reasons, the limitations of claim 10 are not found to patentably distinguish the claimed invention from that of the prior art.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over CN 114149958 A to Li et al., published 2022-03-08, as applied to claims 1-3, 5-11, 17-19 and 22-23 above; in further view of Matti et al. (2021) “An alternative way to perform diagnostic nasopharyngeal swab for SARS-CoV-2 infection” American Journal of Otolaryngology, 42(2), 102828, 4 pages.
This rejection is newly applied, necessitated by amendment.
Dependent claim 20 recites that the swabbing step uses a brush to access the nasopharynx of the human subject via the oral cavity of the human subject. In contrast, Li discloses the nasopharyngeal swabs are inserted into the nasal cavity of the subject for sampling. See, page 2 of the translation.
Matti is relevant prior art for teaching an alternative way to perform nasopharyngeal swabbing for subjects having a coronavirus infection. In patients with severe coagulopathies or diseases such as HHT, nasopharyngeal swabbing through the nasal cavity possesses the risk of nose-bleeding, and, for subjects having conditions like advanced stage sinonasal neoplasms or unfavorable anatomical characteristics, such swabbing may not be feasible. To address this problem, Matti developed a modified oropharyngeal swab having an angled segment towards the sampling end such that the modified swab reaches the nasopharynx of a human subject when inserted into the oral cavity. See, Abstract, pages 1-2, and Figures 1-2.
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 Li by accessing the nasopharynx of the human subject via the oral cavity using a modified oropharyngeal swab, as found in Matti, with a reasonable expectation of success because accessing the nasopharynx via the nasal cavity may not be feasible, or may pose the risk of nose-bleeding, in subjects with particular complications, such as severe coagulopathies, diseases like HHT, advanced stage sinonasal neoplasms and unfavorable anatomical characteristics.
Regarding dependent claim 21, Matti discloses the modified oropharyngeal swab has an angled segment towards the sampling end such that the modified swab reaches the nasopharynx of a human subject when inserted into the oral cavity. See, page 2 and Figure 1. Such a structure may be considered as resembling a hockey stick.
Claims 4 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over CN 114149958 A to Li et al., published 2022-03-08, as applied to claims 1-3, 5-11, 17-19 and 22-23 above; in further view of 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.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 4, Li discloses the organoid medium contains fibroblast growth factors. See, page 2 of the translation. Li does not disclose that the media contains fibroblast growth factor, R-spondin and Noggin.
Rajan is relevant prior art for disclosing a non-invasive method for generating human three-dimensional nasopharyngeal organoids (human nose organoids, HNOs), wherein the method comprises non-invasively collecting nasopharyngeal samples via nasal washes and mid-turbinate swabbing, 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.
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The niche factors comprise fibroblast growth factor (FGF), R-spondin 1 and Noggin. See, airway organoid (AO) media recipe in Supplementary Table 1. Rajan further teaches passaging the organoids on day 14 using an enzyme (trypsin) and/or mechanical shearing. See, e.g., Abstract; pages 2-3, and 11; and Figure 1.
The organoids are described as having a spherical structure (fig. 1A-C), a diameter of approximately 70 μm (fig. 1C, based on scale bar), and a differentiated cell population comprising KRT5+ basal cells, SCGB1A1/CC10+ secretory club cells, MUC5AC+ goblet cells, and acetylated-α-Tubulin+ ciliated cells (pg. 2-3, 12; fig. 1E-G).
Therefore, prior to the effective filing date of the instantly claimed invention, one of ordinary skill in the art would have recognized that the media compositions of either Li or Rajan would have been suitable for the generation of airway organoids comprising basal cells, secretory club cells, goblet cells and ciliated cells. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to substitute the media composition of Li with the media composition of Rajan, which comprises FGF, R-spondin and Noggin, with a reasonable expectation of success because the Rajan’s media composition successfully generated organoids which could be maintained and passaged in vitro while retaining the in vivo characteristics of human airway epithelia (Results, pg. 3), and 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 15, Rajan teaches a step of dissociating the one or more three-dimensional human nasopharyngeal organoids into a single cell suspension, and seeding the cells in an insert pre-coated with bovine collagen I until reaching a confluent monolayer, i.e., in generating air-liquid interface (ALI) cultures. The ALI cultures retained the in vivo characteristics of human airway epithelia and provided useful models of respiratory virus infection. See, e.g., Abstract; pages 2-3, and 11; and Figure 1.
However, Rajan teaches the type I collagen is bovine type I collagen, and claim 15 recites the type I collagen is rat tail type I collagen. Nonetheless, rat tail was known in the art as a source of type I collagen for cell culture prior to the effective filing date of the instantly claimed invention. Official Notice taken, if necessary. Accordingly, one of ordinary skill in the art would have understood that either rat tail type I collagen or bovine type I collagen may be suitable for culturing airway organoids. Therefore, 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 previously 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
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 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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