DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response to restriction requirement filed on November 17, 2025 have been received and entered. Claims 1, 49 and 50 are pending in the instant application.
Election/Restrictions
Applicant’s election of claims 33-39 (group II) in the reply filed on November 17, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1, 40-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 17, 2025.
Priority
This application is a 371 of PCT/US2021/062007 filed on 12/06/2021, which claims priority from US provisional application no 63/122,416 filed on 12/07/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/17/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claims 33-39 are under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 34 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 34 is vague and indefinite because it recites an incomplete claim. The metes and bounds of the claims could not be ascertained. Appropriate correction is required.
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 33, 35-39 are rejected under 35 U.S.C. 103 as being unpatentable over Keck (US20180187210, dated 7/5/2018), Wahl (Nat Biotechnology. 2019 Oct;37(10):1163-1173, 8/26/2019) as evidenced by Wu (PLoS Pathog 2017, 13(4): e1006281, 1-24).
.Claims are directed to a method comprising: administering to an immunodeficient mouse cells of a human patient-derived xenograft (PDX), wherein the cells comprise a pathogen entry moiety; and administering to the immunodeficient mouse a pathogen comprising a surface moiety that binds to the pathogen entry moiety.
With respect to claim 33, Keck teaches a method comprising
(i) administering human patient-derived xenograft (PDX). to an immunodeficient NSG mouse (page 9 and 11), wherein PDX is tumor of a lung, colon, bladder or ovarian cancer (see para. 22-23), and further comprising administering to the immunodeficient (NSG or BLT-NSG) mouse human hematopoietic stem cells (HSCs) along with PDX. In some embodiments, PDX is introduced into the mice before the engrafted human immune cells (e.g., human B- or T-cells or NK cells) appear (see para. 150).
Regarding claims 35, Keck teaches the administering is by tail vein injection, subcutaneous, cardiac injection, caudal artery injection, cranial injection, hepatic artery injection (see para. 107).
With respect to claim 36-37, Keck teaches a method further comprising administering to the mouse a therapeutic agent cisplatin to assess the toxicity of the agent showing reduction in tumor (see para. 184, 193-194). It is further disclosed that engrafted tumors appear to evade human immunity much as they do in the patients from which they were derived. Moreover, treatment with a TIL check-point inhibitor presumably releases T-cells from anergy and stimulates their cytotoxicity towards the tumor (see para. 206).
Keck differs from claimed invention by not disclosing administering to the immune-deficient mouse a virus to the cells comprises a virus entry moiety and a virus comprising a surface moiety that binds to the pathogen entry moiety.
Wahl cure the deficiency by disclosing transplanting a humanized immunocompromised mouse with ectopically transplanted human lung tissue and human immune cells via bone marrow transplantation to study the infection of respiratory viruses (see fig. 1). It is further disclosed that MERS-CoV or HCMV is inoculated directly into the human lung implants (See page 1164, col. 1, last para, col. 2, para. 5).
Regarding claims 36-38, Wahl teach administering ganciclovir (GCV) to said immunodeficient mouse to treat or prevent infection by HCMV n (see page 1164, col. 2, last para.).
With respect to claim 39, Wahl teaches method further comprising assessing viral load in the mouse (see page 1161, col. 1, last para to col. 2, para. 1., fig. 2).
The combination of reference does not specifically recite inherent feature of virus to the cells comprise a virus entry moiety and a virus comprising a surface moiety that binds to the pathogen entry moiety.
However, before the effective filing date of instant application, it was known in prior art that PDGFR-α functions as an entry receptor tor for HCMV expressing gH/gL/gO (see abstract). It is further disclosed that gH/gL/gO—PDGFR-αinteraction starts the predominant entry pathway for infection of the lung fibroblasts (see Wu et al abstract and page 3).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art modify the method of Keck by administering a virus as suggested by Wahl, in the method of evaluating lung function following viral infection, with a reasonable expectation of success, at the time of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because humanized mouse models disclosed in prior art is reported to support infection and replication of important human viral pathogens that could be used to study other human pathogens that target the lung (for example, enterovirus D68, adenovirus type 7, influenza virus, rhinovirus and metapneumovirus), accelerating the in vivo testing of preventative and therapeutic approaches for potential agents (see page 1171, col. 2, last para.). Other limitation of lung cells comprises a pathogen entry moiety and virus comprising a surface moiety that binds to the viral entry moiety would be inherent in view of the teaching of Wu. One of skill in the art would have been expected to have a reasonable expectation of success in infecting the lung cells derived from xenograft because prior art teaches the successful infection with virus comprising coat glycoprotein that binds to surface receptor on the surface of the lung cells as evident from the teaching Wahl in view of Wu . It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 33, 34 are rejected under 35 U.S.C. 103 as being unpatentable over Keck (US20180187210, dated 7/5/2018), Wahl (Nat Biotechnology. 2019 Oct;37(10):1163-1173, 8/26/2019) as evidenced by Wu (PLoS Pathog 2017, 13(4): e1006281, 1-24) as applied above and further in view of Xian (WO2014152321, 9/21/2014). Claim interpretation: Claim 39 is interpreted as wherein the cells are administered sample of the single cell suspension.
The teaching of Keck, Wahl and Wu have been described above and relied in same manner here. The combination of references differs from claimed invention by not disclosing wherein the cells are administered sample of the single cell suspension.
Xian teaches picking a single colony to develop a pedigree cell line, where cell line has been derived from a single cell (page 125, first paragraph; page 131 third paragraph to last paragraph). It is further disclosed that the administered sample of the single cell suspension is delivered by pipetting (page 131, last paragraph; parage 133, last paragraph).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art modify the method of Keck and Wahl by administering the cells are sample of the single cell that are suspension is delivered by pipetting, as suggested by Xian, in the method of evaluating lung function following viral infection, with a reasonable expectation of success, at the time of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because it provides evaluation of therapeutics in a sample derived from a single cell clone. One of skill in the art would have been expected to have a reasonable expectation of success in infecting the lung cells derived from xenograft because prior art teaches the successful infection with virus comprising coat glycoprotein that binds to surface receptor on the surface of the lung cells as evident from the teaching Wahl in view of Wu . It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claim Rejections - 35 USC § 112-written description
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.
Claims 33-39 are 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.
The claim embraces use of an immunodeficient mouse cells of a human patient-derived xenograft (PDX), wherein the cells comprise a pathogen entry moiety; and use of any pathogen comprising a surface moiety that binds to the pathogen entry moiety. Thus, claims encompass a genus of cells of a PDX, wherein the cells comprise any pathogen entry moiety and use of genus of pathogen comprising any surface moiety that binds to the pathogen entry moiety.
In analyzing whether the written description requirement is met for the genus claim, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. Vas-Cath Inc. v. Mahurkar , 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that ''applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.'' Vas-cath Inc. v. Mahurkar , 19USPQ2d at 1 117. The specification does not ''clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.'' Vas-cath Inc. v.Mahurkar , 19USPQ2d at 1116.
The genus the mouse cells of a human PDX, wherein the cells comprise any pathogen entry moiety and plurality of different pathogen comprising any surface moiety that binds to the pathogen entry moiety is embraced by the breadth of the claim. The specification contemplates host cell moiety is selected from membrane proteins, lipids, and carbohydrate moieties, optionally present either on glycoproteins or glycolipids, whereas the pathogen is selected from bacteria, viruses, prions, and fungi (see page 2 of the specification) subsequently limiting to he pathogen is a virus that is selected from a group consisting of a respiratory virus such as influenza viruses, respiratory syncytial viruses, parainfluenza viruses, adenoviruses, and coronaviruses (see page 3 of the specificaton0.
The art teaches successful targeting across different pathogen type depends on receptor binding. For instance, Noyce et al (PLoS Pathog7(8):e1002240., 1-24) teaches d Nectin-4 (PVRL4) as the long-sought epithelial cell receptor for the measles virus (MV) (see abstract). Wiles (Exp Mol Pathol. 2008 Apr 8;85(1):11–19) teaches diversity of known and putative UPEC-associated virulence genes, coupled with high levels of genetic overlap seen among both pathogenic and nonpathogenic extraintestinal E. coli isolates. This makes it difficult to attribute UPEC virulence to any one set of factors. Rather, it is likely that UPEC and other ExPEC strains have evolved multiple and redundant mechanisms to overcome the many challenges encountered within the host environment. (page 9 last para). Wiles concludes that multiple adhesions compensate for receptor differences and binding is not sufficient for colonization. In view of foregoing, it is apparent that many bacterial receptors binding would not reliably predict colonization. In view of foregoing, it is apparent that while receptor is necessary for many pathogens, however, many pathogens such as bacterial infection is a multistep and may involve redundant processes. In the instant case, specification did not demonstrate a reduction to practice of a genus of cells comprising a pathogen entry moiety and plurality of different pathogen comprising a surface moiety that binds to the pathogen entry moiety, nor did Applicant adequately describe the distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of cells comprise a pathogen entry moiety and use of plurality of different pathogen comprising a surface moiety that binds to the pathogen entry moiety as embraced by the breadth of the claims.
The specification exemplified SARS-CoV-2 and human ACE2 levels in PDX-humanized mice after intranasal (IN) or intravenous (IV) infection with SARS-CoV-2 compared to uninfected (Un) mice (See fig. 3). Figure 8 shows SARS-CoV-2 infections in NSG mice humanized with different PDXs. (example 2). Based upon the prior art as discussed above is expected to be variation among different species of cell comprising entry moiety and different species and subspecies of pathogen comprising a surface moiety that binds to the pathogen entry moiety. There is no evidence on the record of a relationship between the entry moiety and surface moiety of the ACE2 and SARC-CoV2 to any of the embraced surface moiety and pathogen that would provide any reliable information about the any other surface moiety and pathogen within the claimed genus.
As such, the Artisan of skill could not conclude that Applicant possessed any additional combination of surface moiety and pathogen that binds to the pathogen entry moiety, except for ACE2 and SARC-CoV2 that is specifically described in specification (see example 2 of the specification). Hence, only ACE2 and SARC-CoV2 could be demonstrated as possessed. There is no evidence on the record that any combination of surface moiety that does not uniquely correspond to the genus of pathogen entry moiety or yet to be identified pathogen entry moiety within the claimed genus.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which is not conventional in the art before the effective filing date of the invention. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics. Inc., 48 USPQ2d 1641, 1646 (1998). As such, the Artisan of skill could not conclude that Applicant possessed any additional species of sequences, except for that of ACE2 and SARC-CoV2.
The skilled artisan cannot envision the detailed chemical structure of the surface moiety and pathogen entry moiety within the claimed genus showing contemplated biological activity other than those described and exemplified in the specification, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen lnc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). In conclusion, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that Applicant is in possession of genus of surface moiety and pathogen entry moiety as broadly claimed at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Ashraf (Physiol Genomics 53: 51–60, Dec. 4, 2020) and Pujhari (Virulence, May 20, 2020. 11(1) 486–488) teaches mice comprising a humanized lung and immune system to study SARS-CoV-2 infections (see figure 1 )..
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/ANOOP K SINGH/Primary Examiner, Art Unit 1632