Prosecution Insights
Last updated: April 19, 2026
Application No. 18/466,854

METHOD FOR ASSESSING RESPIRATORY VIRAL INFECTIONS

Non-Final OA §101§103§112
Filed
Sep 14, 2023
Examiner
PAULUS, ERIN VIRGINIA
Art Unit
1631
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The University of Hong Kong
OA Round
1 (Non-Final)
43%
Grant Probability
Moderate
1-2
OA Rounds
2y 3m
To Grant
99%
With Interview

Examiner Intelligence

Grants 43% of resolved cases
43%
Career Allow Rate
3 granted / 7 resolved
-17.1% vs TC avg
Strong +80% interview lift
Without
With
+80.0%
Interview Lift
resolved cases with interview
Typical timeline
2y 3m
Avg Prosecution
37 currently pending
Career history
44
Total Applications
across all art units

Statute-Specific Performance

§101
8.8%
-31.2% vs TC avg
§103
34.8%
-5.2% vs TC avg
§102
14.5%
-25.5% vs TC avg
§112
32.6%
-7.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 7 resolved cases

Office Action

§101 §103 §112
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 1-13 are pending and examined on the merits. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The instant application claims domestic benefit from U.S. provisional application 63 / 406 , 742 filed on September 15, 2022 . Information Disclosure Statement The information disclosure statements (IDS) submitted on November 3, 2023 and February 24, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Applicant is reminded that 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, 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 appl icant regards as his invention. Claim s 1- 13 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. With regard to claim s 1 , 4, and 10 , t he term “ precision-cut ” in line s 1 , 1, and 2 respectively is a relative term which renders the claim indefinite. The term “ precision-cut ” 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. As claimed, it is not clear how one would determine that a bronchial tissue sample is “precision cut” thus rendering the scope unclear . Appropriate correction is required. Dependent claims 5-9 and 11-13 are included in the basis of the rejections because they do not clarify the scope of “ prescision -cut”. With regard to claim s 1 and 10 , t he term “ cilia-rich ” in line 3 is a relative term which renders the claim indefinite. The term “ cilia-rich ” 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. As claimed, it is not clear what amount of cilia would constitute “cilia-rich” epithelium thus rendering the scope unclear . Appropriate correction is required. Dependent claims 1- 9 and 11-13 are included in the basis of the rejections because they do not clarify the scope of “ cilia-rich ”. With regard to claims 1 and 13 , the limitation “providing a semi-quantitative and normalized approach to supplement data ” appears to omit method steps or other essential elements regarding the details of the broadly-claimed semi-quantitative and normalized approach and how it is to be used to supplement data thus rendering the scope of the claim indefinite. Appropriate correction is required. Dependent claims 1-1 2 are included in the basis of the rejections because they do not clarify the scope of “providing a semi-quantitative and normalized approach to supplement data” . With regard to claim 2 , the term “unwanted tissues” in line 9 is subjective term which renders the claim indefinite. A claim may be rendered indefinite by reference to subjective term (see MPEP 2173.05(b), IV). T he phrase “unwanted tissue ” is not defined by the claim, the specification does not provide a standard for some standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claim 3 is included in the basis of this rejection because it does not clarify the scope of “unwanted” tissue. With regard to c laim 7 , which depends from claim 1, claim 7 recites the limitation "unwanted tissues" in line 1 . There is insufficient antecedent basis for this limitation in the claim as there is no prior recitation of unwanted tissues in claim 1. Appropriate correction is required. With regard to c laim 10 , which depends from claim 1, claim 10 recites the limitation "the virus infection" in line 1. There is insufficient antecedent basis for this limitation in the claim as there is no prior recitation of a virus infection. Appropriate correction is required. With regard to c laim 1 3 , which depends from claim 1, claim 13 recites the limitation "the ex vivo cultures of human bronchus" in line 3. There is insufficient antecedent basis for this limitation in the claim as all prior recitations are to an ex vivo model of human bronchus and ex vivo cultures. Therefore it is unclear if the recited ex vivo culture is intended to differ from the previously recited ex vivo model. Appropriate correction is required. 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 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. MPEP 2106.04 states: In addition to the terms "laws of nature," "natural phenomena," and "abstract ideas," judicially recognized exceptions have been described using various other terms, including "physical phenomena," "products of nature," "scientific principles," "systems that depend on human intelligence alone," "disembodied concepts," "mental processes," and "disembodied mathematical algorithms and formulas." It should be noted that there are no bright lines between the types of exceptions, and that many of the concepts identified by the courts as exceptions can fall under several exceptions. For example, mathematical formulas are considered to be a judicial exception as they express a scientific truth, but have been labelled by the courts as both abstract ideas and laws of nature. Likewise, "products of nature" are considered to be an exception because they tie up the use of naturally occurring things, but have been labelled as both laws of nature and natural phenomena. Thus, it is sufficient for this analysis for the examiner to identify that the claimed concept (the specific claim limitation(s) that the examiner believes may recite an exception) aligns with at least one judicial exception. Claim 1 recites a method for assessing respiratory viral infections and claim 13 depends from claim 1. Claims 1 and 13 are drawn to a statutory category of a process and are eligible under Step 1 . Claim 1 recites “assessing infectivity, tropism, and pathogenesis of one or more respiratory viruses in the ex vivo model and providing a semi-quantitative and normalized approach to supplement data from the ex vivo model…”. The broadest reasonable interpretation of “assessing” includes observation and decision-making and the broadest reasonable interpretation of “providing a semi-quantitative and normalized approach” is application of mental concept or framework. Thus, claim 1 recites a concept that falls into the mental processes group of abstract ideas. Claim 13 recites “the step of providing a semi-quantitative and normalized approach comprising utilizing a post-staining or scoring analysis”. Per Example 5 and Fig. 3 on pages 12-13 of the specification, the post-staining or scoring analysis is a determination of the percentage of cells in a tissue sample exposed to a virus which are antigen-positive based on staining, which could be performed via observation and estimation or manual counting . Subsequently, a label is given to each tissue sample based on the percentage of antigen-positive cells (i.e., sparse, +, ++, +++, or -) and the assessed level of viral infectivity is determined based on the percentage of antigen-positive cells and the associated label . Thus, the post-staining or scoring analysis is performed via estimation and/or counting and associated decision-making and therefore recites concepts that fall into the mathematical concepts and /or mental processes group of abstract ideas. Thus , claims 1 and 13 are drawn to the judicial exception of abstract ideas under Step 2A, Prong One . This judicial exception is not integrated into a practical application because the additional method steps are no more than insignificant extra-solution activity and mere instructions to apply an exemption . Claim 1 recites additional steps of preparing one or more precision-cut human bronchial tissues and exposing cilia-rich epithelium within the bronchial tissues to establish an ex vivo model . These method steps are performed in order to generate the conditions required for use of the recited judicial exception of assessing infectivity, tropism, and pathogenesis and providing a semi-quantitative and normalized approach to supplement data from the ex vivo model. Claim 13 provides additional limitations regarding the details of the semi-quantitative and normalized approach used to supplement data. The claim limitations to providing a semi-quantitative and normalized approach to supplement data from the ex vivo model for pandemic risk assessment utilizing post-staining or scoring analysis comprise the judicial exception of abstract ideas with no details of how to implement the abstract idea into a meaningful practical application beyond general instructions to apply the abstract idea to the ex vivo model. Thus, the judicial exceptions are not integrated into a practical application under Step 2A, Prong Two . The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception under Step 2B because the instant disclosure teaches well-understood, routine, and conventional methods which are implemented for the steps of preparing one or more bronchial tissue samples and exposing the cilia rich epithelium which would be well known to one having ordinary skill in the art, as shown in the prior art references of Chan 2013a and Chan 2013b applied below in the 103 rejections. Both Chan 2013a and Chan 2013b teach use of a human bronchial tissue samples and the ciliated epithelium (see Chan 2013a Supplemental annex) in order investigate infectivity, tropism, and pathogenesis of respiratory viruses . Thus, the additional elements recited in the claims are no more than well-understood, routine, and conventional activities commonly known in the art under Step 2B . 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. 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, 4- 6 , and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Cha n, MC et al. (2013, Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract. The Lancet Resp. Med. , 1 (7), 534-542 , found in IDS dated 11/03/2023, hereafter “Chan 2013a”). With regard to claim 1 , Chan 2013a teaches investigation of a novel influenza A H7N9 virus in comparison to known influenza A viruses , which is considered to reasonably read on assessing respiratory viral infections , comprising a comparison of tropism, replication, and infection patterns across influenza viruses in order to investigate the pathogenesis of the novel H7N9 virus and, ultimately, H7N9’s overall risk as a pandemic threat (Abstract). Chan 2013a teaches use of ex vivo tissue samples from human bronchus (Abstract) wherein fresh human bronchus biopsies (Supplementary appendix, Pg. 7, Ex vivo culture of human respiratory tract) were cut into multiple 2-3 mm fragments (Supplementary appendix, Pg. 7, Influenza virus infection of ex vivo cultures), which is considered to reasonably read on “precision-cut” human bronchial tissues. Chan 2013a does not directly teach exposure of “cilia-rich” epithelium within the bronchial tissues, however, Chan 2013a does teach assessment of viral infection in ciliated bronchial epithelial cells (Abstract ; Fig. 2 ; Pg. 539, left col., 1 st para.). Therefore, one having ordinary skill in the art would recognize that ciliated cells w ould be located in the epithelium of bronchial tissues and that those cells would need to be exposed in order to assess viral infection in ciliated cells. Additionally, Chan 2031a teaches that individual genetic and environmental variability associated with donors of bronchial tissue samples may result in differing infection phenotypes and that genetic or other host factors could play a role in infection susceptibility (Pg. 539, left col., 1 st para., lines 16-22). Chan 2013a teaches that supplemental data from patients/individuals is important in understanding the pathogenesis of H7N9 (Pg. 540, left col., 2 nd full para.) and highlights a need for investigation of the reported differences between the novel H7N9 virus and other known avian influenza viruses, particularly investigation into the biological basis related to reports of increased H7N9 infection occurrence in older patients and increased disease seve rity associated with increased age (Pg. 540, right col., 1 st para.). This is considered to reasonably read on a semi-quantitative and normalized approach to supplement data. Further , Chan 2013a teaches overall comparison of the replication kinetics (Fig. 1 A ) and tropism (Fig. 2 A, C, E, and G ) of H7N9 with those of known highly pathogenic avian influenza viruses and known low pathogenic avian influenza viruses (Abstract) in order to determine whether the novel H7N9 virus is adapted for infection of mammalian species and , therefore, would represent a pandemic risk (Pg. 541, right col., last para.) This is also considered to reasonably read on a semi-quantitative and normalized approach to supplement data. Therefore, Chan 2013a teaches wherein a semi-quantitative and normalized approach can be used alongside data from an ex vivo bronchial tissues in order to assess pandemic risk of a respiratory virus. With regard to claim 4 , Chan 2013a teaches that the bronchial tissues are incubated with a sterile surgical pathology sponge to establish an air-liquid interface in 24-well culture plates (Supplemental appendix, Pg. 7, Ex vivo culture of human respiratory tract) . Although Chan 2013a is silent as to positioning such that the airway epithelium is facing upwards, Chan 2013a teaches culture of ex vivo bronchial tissues for subsequent viral infection (Supplementary appendix, Pg. 8, Influenza virus infection of ex vivo cultures) and assess ment of infection in epithelial cells (Pg. 536, Results, 1 st and 2 nd paras. And Fig. 2). Therefore, one having ordinary skill in the art would recognize that facing the epithelial surfac e upward would be beneficial in order to perform subsequent experiments. With regard to claim 5 , Chan 2013a teaches that the bronchial tissues are placed into culture medium and incubated at 37°C (Supplemental appendix, Pg. 7, Ex vivo culture of human respiratory tract). With regard to claim 6 , Chan 2013a teaches that the culture medium is F-12K nutrient mixture with L-glutamine, and antibiotics (Supplemental appendix, Pg. 7, Ex vivo culture of human respiratory tract). With regard to claim 9 , Chan 2013a teaches wherein the respiratory viruses comprise influenza A viruses (i.e., influenza A H7N9, H5N1, H7N7, and H1N1) (Abstract). With regard to claim 10 , Chan 2013a teaches wherein the ex vivo bronchial tissues were infected using a viral titer of 1x10 6 TCID 50 /ml and incubated at 37°C (Supplementary appendix, Pg. 8, Influenza virus infection of ex vivo cultures). Chan 2013a is silent as to the CO 2 percentage in that particular method. However, Chan 2013a indicates that incubator settings of 37°C and 5% CO 2 are used for maintenance of alveolar epithelial cell culture ( Supplementary appendix, Pg. 6, Human alveolar epithelial cells isolation) and human pneumocyte and macrophage cultures ( Supplementary appendix, Pg. 7, Infection of human pneumocytes and peripheral blood monocyte derived macrophages in vitro). Therefore, one of ordinary skill in the art could have reasonably ascertained that incubator settings of 37°C and 5% CO 2 could be used for incubation of ex vivo bronchial tissues with a reasonable expectation of success and would have been motivated to use these settings in order to standardize experimental conditions across cell and tissue cultures. With regard to claim 11 , Chan 2013a teaches wherein , after viral infection, viral replication in bronchial tissues was determined via assessing viral yield in the cell free supernatant from bronchial tissue samples at 1, 24, and 48 hours post infection and wherein increasing viral titers in cell supernatants indicated productive virus replication ( Supplementary appendix, Pg. 8, Influenza virus infection of ex vivo cultures and Fig 1A). With regard to claim 12 , Chan 2013a teaches wherein , after viral infection, bronchial tissues are incubated for 24 hours and then the tissues are fixed in 10% formalin and processed for immunohistochemi cal staining (Supplementary appendix, Pg. 8, Influenza virus infection of ex vivo cultures and Fig. 2 ). With regard to claim 13 , Chan 2013a teaches a post-staining analysis comparing the viral infection of the novel H7N9 virus to viral infection of H5N1 in bronchial tissues (Fig. 2 A, C, E, and G and Pg. 536, Results, 2 nd para.) as well as a post-staining scoring analysis comparing viral infection of the novel H7N9 virus to viral infection of other avian influenza viruses in bronchial tissues (Table 1 and Pg. 536, Results, 2 nd para.) Claims 2-3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Chan 2013a as applied to claims 1, 4-6, and 9-13 above, and further in view of Chan, MC et al. (2010. Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract. American J. of Path. , 176 (4), 1828-1840, found in IDS dated 11/03/2023, hereafter “Chan 2010”) , Yaghi et al. (2010. Primary human bronchial epithelial cells grown from explants. JoVE , (37), 1789, hereafter “ Yaghi ”) and Bals et al. (2004). Isolation and air–liquid interface culture of human large airway and bronchiolar epithelial cells. J. of Cystic Fibrosis , 3 , 49-51, hereafter “Bals”) . With regard to claim 2 , as detailed above, Chan 2013a teaches investigation of a novel influenza A H7N9 virus in comparison to known influenza A viruses comprising a comparison of tropism, replication, infection patterns across influenza viruses in order to investigate the pathogenesis of the novel H7N9 virus and, ultimately, H7N9’s overall risk as a pandemic threat (Abstract). Chan 2013a teaches use of ex vivo tissue samples from human bronchus (Abstract) wherein fresh human bronchus biopsies were obtained from patients undergoing surgical resection of lung tissue and cut into multiple 2-3 mm fragments (Supplementary appendix, Pg. 7, Influenza virus infection of ex vivo cultures) , which is considered to reasonably read on collecting bronchial tissues from at least one patient and cutting tissue samples into squares . Chan 2013a does not teach the wherein the bronchial tissue samples were from patients with lung carcinoma, nor does Chan 2013a detail the specific steps for obtaining the bronchial tissue samples. Chan 2013a does teach use of methods previously described and references Chan 2010 (Supplementary appendix, Pg. 5, In vitro and ex vivo cell cultures and Pg. 11, References). Chan 2010 teaches investigation of the pathogenesis of a novel H1N1pdm influenza A virus by comparison of tropism , viral replication and host response to H1N1pdm virus with known other H1N1 influenza A viruses in ex vivo human bronchial tissue (Abstract). Chan 2010 teaches wherein bronchi were obtained from lung carcinoma patients undergoing surgical resection. Chan 2010 further teaches wherein bronchial tissues were placed in culture medium comprising F-12K nutrient mixture with L-glutamine and antibiotics, incubated at 37°C with a sterile surgical pathology sponge to establish an air-liquid interface in 24-well culture plates prior to viral infection experiments (Pg. 1831, Ex vivo Culture of Conjunctiva, Nasopharynx, Bronchi, and Lung). Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the bronchial tissues obtained from lung carcinoma patients as taught by Chan 2010 for the bronchial tissues obtained from patients undergoing surgical resection as taught by Chan 2013a with a reasonable expectation of success. Based on the similarity of the culture methods and subsequent viral infection experiments, a skilled artisan would have recognized that bronchial tissue from lung carcinoma patients could be used in the method of Chan 2013a with the same expected results. One having ordinary skill in the art would have been motivated to make this combination in order to maximize the types of patient bronchial samples available for use in the method as only a limited population of individuals are likely to undergo lung resection surgery. The combination of Chan 2013a and Chan 2010 are silent as to the specific details of the method steps by which the human bronchial tissues are prepared. Yaghi teaches a method of preparation of human bronchial explants harvested during lung surgery, including surgery for lung cancer (Abstract). Yaghi teaches wherein bronchial tissue samples are placed in a petri dish, thoroughly rinsed with cold Earle’s Balanced Salt Solution (EBSS) (Abstract and Protocol, 2. Preparing Bronchial Tissue Explants), and excess parenchymal tissue is removed (Abstract) . Yaghi teaches that the bronchial tissue segments are “cut open” and cut into 2-3 mm pieces and wherein small scissors and forceps which have been sterilized using 70% ethanol (Protocol, 1. Coating and Scratching 100mm Culture Plates) can be used in order to cut and move the bronchial tissue pieces (Protocol, 2. Preparing Bronchial Tissue Explants). Further, Yaghi teaches that this method can be used to prepare bronchial explants which can be cultured on an air-liquid interface (Discussion). Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the bronchial explants prepared by the method as taught by Yaghi for the ex vivo bronchial tissue cultures used in the method of assessment of infectivity, tropism, and pathogenicity of respiratory viruses as taught by Chan 2013a with a reasonable expectation of success. As Chan 2013a is silent as to the specific details of the method of bronchial tissue collection and both Chan 2013a and Yaghi teach harvesting of bronchial tissues which can be used in an air-liquid interface culture , a skilled artisan would have recognized that the human bronchial explants as taught by Yaghi could have been substituted for the ex vivo human bronchial tissues as taught by Chan 2013a with the predictable result of preparing human bronchial tissue cultures which can be cultured in an air-liquid interface and used in subsequent experimental assays. While Yaghi teaches that the bronchial tissue samples are “ cut open ” , Yaghi does not specifically teach a single lengthwise cut to expose airway epithelium nor does Yaghi teach washing bronchial tissue using PBS . Bals teaches a method of isolation and culture of human airway epithelial cells which can be grown in an air-liquid interface (Abstract) wherein the cells can be obtained from lung pieces collected during surgery ( Introduction ). Bals teaches that airways, trachea, or bronchus can be stored in PBS and cleaned up by washing several times in PBS, which a skilled artisan would recognize would remove contaminants including blood, before dissecting away unwanted tissue, and cutting the airway open longitudinally (Pg. 50, left col., Methods, 1 st para.) to expose the epithelium (Pg. 50, right col., 2 nd para.). This is considered to reasonably read on performing one lengthwise cut to open bronchial tissue to expose the luminal surface of the epithelium. While Bals does not teach a second washing step of the bronchial tissue in order to remove surface-attached mucus, Bals does teach removal of mucus during the process of isolating epithelial cells from bronchial tissue (Pg. 50, left col., last line). Thus, one having ordinary skill in the art would recognize that mucus should be removed from isolated human bronchial tissues and, since Bals teaches a previous washing step with PBS, a skilled artisan would recognize that additional PBS rinses could be used in order to remove mucus. Although Chan 2013a, Chan 2010, Yaghi , and Bals do not directly teach wherein the airway epithelium is faced upwards, this is suggested by the teachings of Chan 2013a . Chan 2013a teaches that the bronchial tissues are incubated with a sterile surgical pathology sponge to establish an air-liquid interface in 24-well culture plates (Supplemental appendix, Pg. 7, Ex vivo culture of human respiratory tract). Although Chan 2013a is silent as to positioning such that the airway epithelium is facing upwards, Chan 2013a teaches culture of ex vivo bronchial tissues for subsequent viral infection (Supplementary appendix, Pg. 8, Influenza virus infection of ex vivo cultures) and assessment of infection in epithelial cells (Pg. 536, Results, 1 st and 2 nd paras. And Fig. 2). Therefore, one having ordinary skill in the art would recognize that facing the epithelial surface upward would be beneficial in order to perform subsequent experiments. Therefore it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the use of PBS as a rinsing solution as taught by Bals for the EBSS rinse as taught by Yaghi with a reasonable expectation of success. As both Yaghi and Bals teach rinsing of bronchial tissue, a skilled artisan would have recognized that a PBS rinse as taught by Bals could have been substituted for the EBSS rinse as taught by Yaghi with the predictable result of generating a rinsed bronchial tissue sample. Additionally, it would have been obvious to one having ordinary skill in the art to apply the longitudinal cut used to open the bronchial tissues and expose the luminal epithelium as taught by Bals to the method wherein the bronchial tissue is “cut open” as taught by Yaghi with a reasonable expectation of success. A skilled artisan would have been motivated to make this combination in order to create a bronchial tissue sample which has an exposed luminal epithelium which one having ordinary skill in the art would recognize is necessary for subsequent assessment of viral respiratory infections as taught in Chan 2013a . With regard to claim 3 , as detailed above, Yaghi teaches use of sterilized small scissors, which is considered to reasonably read on surgical fine scissors, to cut the bronchial tissue and forceps to move bronchial tissue pieces (Protocol, 2. Preparing Bronchial Tissue Explants). A skilled artisan would have easily recognized that the small scissors and forceps taught by Yaghi could have been used to perform the longitudinal cut to expose the bronchial epithelium as taught by the combination of Yaghi and Bals. With regard to claim 7 , as detailed above in claim 2, Bals teaches dissecting away unwanted tissues from the bronchial tissue samples. Bals teaches that unwanted tissues can comprise soft tissue, parenchyma (Pg. 50, left col., last para.) and blood vessels (Pg. 50, right col., 2 nd para.). Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to use isolated bronchial tissue cells wherein the soft tissue and blood vessels are removed as taught by Bals to in the method of assessing viral infectivity, tropism, and pathogenesis using isolated bronchial tissue samples as taught by Chan 2013a with a reasonable expectation of success. A skilled artisan would have been motivated to combine these teachings in order to generate bronchial tissue samples comprising fewer unwanted cell types in order to minimize confounding data. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Chan 2013a as applied to claim 1, 4-6, and 9-13 above, and further in view of Chan, RW et al. (2013 , Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. J. of Virology , 87 (12), 6604-6614, hereafter “Chan 2013b ” ) . With regard to claim 8 , as detailed above, Chan 2013a teaches investigation of a novel influenza A H7N9 virus in comparison to known influenza A viruses comprising a comparison of tropism, replication, infection patterns across influenza viruses in order to investigate the pathogenesis of the novel H7N9 virus and, ultimately, H7N9’s overall risk as a pandemic threat (Abstract). Chan 2013a teaches use of ex vivo tissue samples from human bronchus (Abstract) in order to assess and compare replication kinetics (Fig. 1A) and tropism (Fig. 2 A, C, E, and G) of H7N9 with those of known highly pathogenic avian influenza viruses and known low pathogenic avian influenza viruses (Abstract) in order to determine whether the novel H7N9 virus is adapted for infection of mammalian species and therefore, represents a pandemic risk (Pg. 541, right col., last para.). The method taught by Chan 2013a is limited to infection by influenza A viruses and does not teach wherein the respiratory viral infection is coronavirus infection. C han 2013b teaches investigation of the transmissibility and pathogenesis of a novel human betacoronavirus lineage C virus EMC ( HCoV -EMC) in comparison to other known coron aviruses (i.e., low pathogenic HCoC-229E and highly pathogenic SARS- CoV ) comprising comparison of tropism, replication kinetics, and immune responses using human bronchial tissue samples (Abstract). Chan 2013b references the use of similar analysis for assessment of tropism in influenza viruses and association with pandemic potential of viruses (Pg. 6605, left col., 2 nd para.). Additionally , Chan 2013b teaches similar method steps for obtaining bronchial tissue samples from patients undergoing surgical resection of lung tissue , subsequent viral infection, and assessment of viral replication and tropism Pg. 6605, Materials and Methods, Ex vivo organ cultures and infection). Further, Chan 2013b teaches wherein comparison of replication kinetics and tropism (Fig. 1) of novel HCoV -EMC with those of known coronavirus strains can be used to indicate viral pathogenesis in novel virus strains (Pg. 6613, left col., last para.) and ultimately the potential threat of a novel virus (Pg. 6608, right col., 2 nd para.) Therefore, one having ordinary skill in the art, before the effective filing date of the claimed invention, would have recognized that the methods of assessment of influenza viruses as taught by Chan 2013a could have been combined with the methods of assessment of coronaviruses as taught by Chan 2013b with a reasonable expectation of success. As both Chan 2013a and Chan 2013b teach similar method steps and analysis of viral infections, but differ in the types of novel viral infections being investigated, a skilled artisan would have recognized that influenza and coronavirus viral infections could be combined with the predictable result of being able to assess novel influenza and coronavirus viral infections for their infectivity, tropism, and pathogenicity in order to provide information regarding pandemic risk. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ERIN V PAULUS whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-6301 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon-Fri 8 AM-5 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, FILLIN "SPE Name?" \* MERGEFORMAT Doug Schultz can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 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. /ERIN V PAULUS/ Examiner, Art Unit 1631 /ARTHUR S LEONARD/ Examiner, Art Unit 1631
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Prosecution Timeline

Sep 14, 2023
Application Filed
Dec 17, 2025
Non-Final Rejection — §101, §103, §112 (current)

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Patent 11991387
SIGNALING NUMBER OF SUBBLOCK MERGE CANDIDATES IN VIDEO CODING
2y 5m to grant Granted May 21, 2024
Study what changed to get past this examiner. Based on 2 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
43%
Grant Probability
99%
With Interview (+80.0%)
2y 3m
Median Time to Grant
Low
PTA Risk
Based on 7 resolved cases by this examiner. Grant probability derived from career allow rate.

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