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
Applicant’s response filed on 06/23/2026 is duly acknowledged.
Claims 5, 7, 10-12, 18, 22-24, 28, 29, 31-33, 35 and 36 were canceled by applicants per 10/15/2024 claim amendments.
Claims 1-4, 6, 8, 9, 13-17, 19-21, 25-27, 30 and 34 as currently presented (on 10/15/2024) are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-4, 6, 8, 9 and 13-15; drawn to “A method for building an eye disease model or a model carrier…”) in the reply filed on 06/23/2026 (see REM, p. 1) is acknowledged.
Claims 16, 17, 19-21, 25-27, 30 and 34 (non-elected inventions of Groups II-III) have been withdrawn from further considerations.
Claims 1-4, 6, 8, 9 and 13-15 (elected invention of Group I, without traverse; drawn to “A method for building an eye disease model or a model carrier…”) have been examined on their merits in this action hereinafter.
Priority
This application is a 371 of PCT/CN2022/114537 (filed on 08/24/2022), which claims foreign priority from a Chinese application CN 20211057929.4 filed on 09/09/2021.
Objection to Drawings
The drawings submitted by applicants on 06/03/2024 are not of sufficient quality to permit examination (see Fig. 1-12 that are not clear and/or legible for review). Accordingly, replacement drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to this Office action. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Applicant is given a shortened statutory period of TWO (2) MONTHS to submit new drawings in compliance with 37 CFR 1.81. Extensions of time may be obtained under the provisions of 37 CFR 1.136(a) but in no case can any extension carry the date for reply to this letter beyond the maximum period of SIX MONTHS set by statute (35 U.S.C. 133). Failure to timely submit replacement drawing sheets will result in ABANDONMENT of the application.
Objection to Specification
1. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see SPEC, p. 26, [123], for instance). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
2. The specification of record on page 7 recites the limitation for a bacterium (see paragraph [31] on p. 7, lines 10-11) as “bee Enterococcus faecium,”, which should be amended to delete the term “bee” as there does not appear to be a bacterium with such a biological name per se (taken herein as a typographical error). Similar correction on page 13, paragraph [67] of the specification is also required.
Claim Objections
1. Claim 8 (as recited) is objected to because of the following informalities: Claim 8 as presented recites a list of various ocular genes that have been recites as abbreviations, such as “ABCA4”, “ABCC6”, “ABCC9”, etc. Applicant is advised to recite the full names of the genes with abbreviated versions in the parenthesis if needed, at least the first time the name of the gene is recited in a claim, or a claim set. Appropriate correction is required.
2. Claim 15 (as recited) is objected to because of the following informalities: Claim 15 recites the limitation “Achromobacter” (see line 14 of the claim 15), which has not been italicized to represent the genus of the recited bacterium. Appropriate correction 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.
1. Claims 1-4, 6, 8, 9 and 13-15 (as presented) 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.
Claim 1 as presented recites “A method for building an eye disease model or a model carrier, comprising infecting the eye disease model or the model carrier with a microorganism.”
First, it is to be noted that the terms “model” or “model carrier” have not been explicitly defined by the applicants on record (see SPEC, p. 2, [4], for instance). The method as claimed requires the limitations of “building” an eye disease model or a model carrier (taken herein as a method of making) by “infecting the eye disease model or the model carrier with a microorganism”, which appears to be confusing as it is not clear- First, if the “model” represents a theoretical model or an actual animal model; second, it is unclear as to how one can “build” a product (here an “eye disease model or model carrier”), if it already exists and has to be infected with a microorganism (directly or indirectly; see instant dependent claim 2). It is unclear as to why the step of “infecting” is required, if the product, i.e. the “eye disease model or model carrier” already is present. The recitation as presented is ambiguous and confusing, as the metes and bounds of the claimed method of making the product does not appear to be properly defined. None of the dependent claims 1-4, 6, 8, 9 and 13-15 clarify this point, and therefore they are also rejected as being indefinite for the same reasons of record. Appropriate correction is required.
Claim 2 recites the limitations “and the indirect contact with the microorganism means that a retinal barrier is present between an eye and the microorganism”, which appears to be ambiguous because it is not clear if limitation of “an eye” represents the eye of the “eye disease model or model carrier” per se, or it belongs to any other individual, or some other component(s) of the “eye disease model or model carrier”. Clarification and appropriate correction/amendment is required.
Claim 3 recites the limitation "the same individual" in line 2. There is insufficient antecedent basis for this limitation in the claim as claim 1 (from which instant claim 3 directly depends from) has no reasonable basis for “an individual” per se. Appropriate correction is required.
Claim 9 recites the limitation "the CRB1 gene" in line 1. There is insufficient antecedent basis for this limitation in the claim as claim 1 (from which instant claim 9 directly depends from) has no reasonable basis for “a CRB1 gene” per se. The dependency of instant claim 9 should be amended to claim 8 in order to obviate this rejection. Appropriate correction is required.
Claim 15 recites the limitation "the bacteria" in line 1. There is insufficient antecedent basis for this limitation in the claim as claim 1 (from which instant claim 15 directly depends from) has no reasonable basis for “a bacteria” per se. The dependency of instant claim 15 should be amended to claim 14 in order to obviate this rejection. Appropriate correction is required.
Claims 4, 6, 8 and 14 each recite limitations after the term “preferably” (see instant claim 4 reproduced below, for instance), which renders the claimed methods indefinite as it is unclear if the limitations recited following such term/phrase are in fact required by the claimed processes (i.e. part of the claimed process), or presented as exemplary (i.e. for example) components.
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Thus, the metes and bounds of the claimed processes of instant claims 4, 6, 8 and 14 as currently presented are deemed indefinite, and appropriate correction is required.
NOTE: In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
1. Claims 1, 2, 4, 6 and 14 (as presented) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Singh et al (2017; NPL cited as ref. [U] on PTO 892 form).
Claim 1, 2, 4 and 6 as currently presented are as follows:
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Singh et al (2017), while teaching that Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes (see Title, Abstract), disclose the method for building an eye disease model or a model carrier, comprising infecting the eye disease model or the model carrier directly with a microorganism such as Zika virus (ZIKV injected intravitreally in the eye of C57BL/6 mice; see entire section “Methods”; and p. 11 sections “Mice” and “Virus strain and infection”, in particular); wherein the eye disease comprises a ZIKV-induced ocular inflammation (see p. 2, 2nd and 3rd paragraphs; p. 6, last paragraph; and p. 8, last full paragraph); and wherein the model is a non-human animal such as a C57BL/6 mouse (see Abstract, and section “Methods”, p. 11 “Mice”). Thus, the disclosure from Singh et al reasonably meets all limitations of instant claims 1, 2, 4, 6 and 14, as currently presented.
2. Claims 1, 2, 4, 6, 14 and 15 (as presented) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wei Lai (WO 2020/098231 A1, published on 05/22/2020; FOR cited in IDS dated 06/23/0226).
Claim 1 (as presented) is directed to “A method for building an eye disease model or a model carrier, comprising infecting the eye disease model or the model carrier with a microorganism.” (see also limitations of claims 2, 4, 6, 14 and 15 as currently presented).
Wei (2020), while teaching animal models and screening methods for intraocular disease or disorder (see Title, Abstract), disclose the method for establishing an animal model of an ocular disease (such as age-related macular degeneration, AMD), and a method for screening (both in vitro and in vivo) candidate therapeutics (such as chemical drugs, biologic drugs or natural drugs) using the model; wherein the method for preparing the model comprises: infecting a model carrier such as macaques (i.e. non-human animal) with a microorganism such as bacteria Bacillus megaterium, Propionibacterium acnes, Clostridium sp. etc. (by subretinal injection; see [23]-[25], for instance); wherein the model carrier can be a human, a non-human mammal, an organ, a tissue, or a cell; the microorganism can be a bacterium or a virus, and the non-human mammal includes a mouse, a rat, a monkey, etc. (see claims 1-5 and 24; paragraphs [33], [109], [118]-[123], [161], for instance); wherein the infection with Bacillus megaterium results in significant intraocular inflammation, both in vitro and in vivo in model carriers, and thus can act as a model for suitable ocular inflammatory conditions (see [32]-[33], [44], for instance). Thus, the disclosure from Wei reasonably meets the limitations of instant claims 1, 2, 4, 6, 14 and 15, as currently presented.
3. Claims 1-4, 6, 14 and 15 (as presented) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yuan et al (2019; NPL cited as ref. [V] on PTO 892 form).
Claim 1 (as presented) is directed to “A method for building an eye disease model or a model carrier, comprising infecting the eye disease model or the model carrier with a microorganism.”
Claim 3 is directed to “The method according to claim 1, wherein the microorganism is
derived from intestinal bacteria of the same individual or is the same as the intestinal bacteria of the individual.” (it is to be noted that the term “derived” from has not been specifically defined by the applicants on record; see instant SPEC, [8], [43], for instance)
See also limitations of claims 2, 4, 6, 14 and 15 as currently presented.
Yuan et al (2019), while teaching the molecular signatures related to the virulence of Bacillus cereus Sensu lato, a leading cause of devastating endophthalmitis and related pathogenesis (see Title, and Abstract on page 1), disclose the method for preparing an eye disease mouse model (see page 9, “Materials and Methods”, section “Bacterial strains and experimental bacterial endophthalmitis”), wherein the model carrier were all female, wild-type C57BL/6 mice, which have no retinal degeneration such as rd1 and rd8; wherein the endophthalmitis models were established by injecting 1 microliter of phosphate-buffered saline (PBS, pH 7.4) comprising 100 CFU bacteria into the vitreous chamber of the eyes (i.e. direct contact with microorganism); wherein the bacterial strains were Bacillus sp. strains LY557, LY178, and LY7 which were clinical isolates from patients already diagnosed with posttraumatic ophthalmitis; wherein they disclose the fact that “Phylogenetic analysis revealed that the pathogenic intraocular isolates belonged to Bacillus cereus, Bacillus thuringiensis and Bacillus toyonensis” (see Abstract), and that “Through incorporating publicly available genomes for Bacillus spp., we found that the intraocular pathogens could be isolated independently but displayed a similar genetic context. In addition, our data provide genome-wide support for intraocular and gastrointestinal sources of Bacillus spp. belonging to different lineages. Importantly, we identified five molecular signatures of virulence and motility genes associated with intraocular infection, namely, plcA-2, InhA-3, InhA-4, hblA-5, and fliD using pangenome-wide association studies…” (see Abstract on p. 1; and disclosure on p. 6-7, Figs. 3-4; and entire section of “Discussion”, 2nd paragraph in particular); and wherein they disclose the results validating “that the intraocular isolates of Bacillus spp. directly caused severe intraocular inflammation and retinal damage leading to vision loss.” (see p. 5, 1st paragraph; Fig. 2). Thus, the disclosure from Yuan et al reasonably meets all the limitations of claims 1-4, 6, 14 and 15, as currently presented.
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.
1. Claims 1-4, 6, 8, 9, and 13-15 (as presented) are rejected under 35 U.S.C. 103 as being unpatentable over Bogale et al (2015; NPL cited in IDS dated 06/23/2026, citation no. 1) taken with Yuan et al (2019; NPL cited as ref. [V] on PTO 892 form) and Fighting Blindness Canada (document cited herein as “FBC 2019”; NPL cited as ref. [W] on PTO 892 form).
Claim 1 (as presented) is directed to “A method for building an eye disease model or a model carrier, comprising infecting the eye disease model or the model carrier with a microorganism.”
Claim 3 is directed to “The method according to claim 1, wherein the microorganism is
derived from intestinal bacteria of the same individual or is the same as the intestinal bacteria of the individual.”
See also limitations of dependent claims 2, 4, 6, 8, 9, and 13-15, as currently presented.
Bogale et al (2015), while studying the differences in the distribution, phenotype and gene expression of subretinal microglia/macrophages in C57BL/6N (Crb1 rd8/rd8) versus C57BL6/J (Crb1 wt/wt) mice (see Title, Abstract, Background last paragraph, and Methods section “Animals”), disclose the mouse model/model carrier with a retinal disease-causing mutation in an ocular Crb1 gene which is a homozygous Rd8 mutation with phenotype C57BL/6N (Crb1 rd8/rd8); wherein when compared with wild-type mice having normal retinas (C57BL6/J (Crb1 wt/wt), C57BL/6N mice having Rd8 mutation demonstrate increased accumulation of subretinal MG/MΦ, displaying phenotypical, morphological, and gene-expression characteristics consistent with a pro-inflammatory shift that became more prominent with aging suggesting that other factors/genes may also modulate the ocular phenotype induced by rd8 mutation of the Crb1 in the mouse model for ocular/retinal diseases (see Abstract, Fig. 1-2, 8; and sections “Inflammatory and oxidative stress genes are differentially expressed in the retinal pigment epithelium and retina of rd8 mutant mice compared to wild-type mice”, and “Conclusions”).
However, Bogale et al do not disclose preparation of an ocular disease model/model carrier by infecting (directly or indirectly) the model or model carrier with a microorganism such as an intestinal bacterium of the model/model carrier (see instant claims 1-3 and 13-15).
Yuan et al (2019), while teaching the molecular signatures related to the virulence of Bacillus cereus Sensu lato, a leading cause of devastating endophthalmitis and related pathogenesis (see Title, and Abstract on page 1), disclose the method for preparing an eye disease mouse model (see page 9, “Materials and Methods”, section “Bacterial strains and experimental bacterial endophthalmitis”), wherein the model carrier were all female, wild-type C57BL/6 mice, which have no retinal degeneration such as rd1 and rd8; wherein the endophthalmitis models were established by injecting 1 microliter of phosphate-buffered saline (PBS, pH 7.4) comprising 100 CFU bacteria into the vitreous chamber of the eyes (i.e. direct contact with microorganism); wherein the bacterial strains were Bacillus sp. strains LY557, LY178, and LY7 which were clinical isolates from patients already diagnosed with posttraumatic ophthalmitis; wherein they disclose the fact that “Phylogenetic analysis revealed that the pathogenic intraocular isolates belonged to Bacillus cereus, Bacillus thuringiensis and Bacillus toyonensis” (see Abstract), and that “Through incorporating publicly available genomes for Bacillus spp., we found that the intraocular pathogens could be isolated independently but displayed a similar genetic context. In addition, our data provide genome-wide support for intraocular and gastrointestinal sources of Bacillus spp. belonging to different lineages. Importantly, we identified five molecular signatures of virulence and motility genes associated with intraocular infection, namely, plcA-2, InhA-3, InhA-4, hblA-5, and fliD using pangenome-wide association studies…” (see Abstract on p. 1; and disclosure on p. 6-7, Figs. 3-4; and entire section “Discussion”); and wherein they disclose the results validating “that the intraocular isolates of Bacillus spp. directly caused severe intraocular inflammation and retinal damage leading to vision loss.” (see p. 5, 1st paragraph; Fig. 2). Although, Yuan et al disclose that specific bacterial strains isolated from patient’s intraocular lesions/locations, may have evolved independently, nevertheless, they do provide support for their relationship with the gastrointestinal origin and/or source (see page 8, 1st paragraph; and “Conclusions”) in development of ocular diseases, including Bacillus endophthalmitis.
FBC 2019, while teaching the influence of diet on an individual’s gut microbiome and intestinal permeability, specifically in relation to the ocular physiology and pathology (see sections “Gut Microbiota”, “High fat diet and gut permeability”), disclose the fact that in subjects with compromised gut permeability, the intestinal bacteria may gain access to the body’s circulatory system and thus access various tissue and organs, including ocular tissues such as retinal tissues, and induce inflammatory responses. Although the document FBC 2019 does not disclose an animal model for such effects of intestinal commensal bacteria, they nevertheless clearly implicate the intestinal permeability of an individual with the leakage of the intestinal bacteria into the blood circulation and other organs including ocular tissues and its role in development of ocular inflammation and/or related diseases.
Thus, given the detailed disclosure from Yuan et al when taken with the disclosure from FBC 2019 document, it would have been obvious to an artisan of ordinary skill in the art to prepare an animal model by infecting a model carrier (as already disclosed by Bogale et al, above) with a microorganism such as its own intestinal bacterial species/strains (as taught by Yuan et al, above) that can provide a reasonable model for ocular disease and/or disorders, including retinal pathologies (for the effect of gut microbiota in relation to subject’s dietary input, gut permeability, and relationship to developing ocular disease; as suggested by FBC 2019 document, discussed above), as per need. Since, Bogale et al already disclose the suitable mouse model or model carrier (such as mouse Crb1 gene with rd8 mutation) for retinal inflammation and related ocular diseases, and since they already recognized the role of other factors with age that play an important role in developing retinal disfunction and/or inflammation (see Bogale et al, “Conclusions”, for instance), an artisan in art of ocular disease and/or pathologies, would have been motivated to employ subject’s own (i.e. commensal) intestinal/gut bacteria or derived strains therefrom (as suggested by Yuan et al when taken with disclosure for the effect of gut permeability on the intestinal bacterial leakage and its resulting effects on ocular disorders in a subject by FBC 2019 document) in order to provide a better animal model for the desired ocular disease including retinal inflammatory conditions or disorders, with a reasonable expectation of success (as Bogale et al already provides details for the specific mouse and techniques required for assessment and/or evaluation of the progress of the retinal disorders; see discussion above, and Bogale et al, Figs. 1-2, 7 and 8, for instances). Unless evidence/data provided on record to the contrary (which is currently lacking on record; see instant SPEC, Examples 7-10), such modification in the model or model carrier (that employs infecting the mouse model/carrier with suitable intestinal bacterial strain) as taught by the combined teachings of the cited prior art reference as discussed above, would have been obvious and/or fully contemplated by an artisan of ordinary skill in the art.
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as generically claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Conclusion
NO claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
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