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 .
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.
Election/Restrictions
Applicant’s election without traverse of species A-H in the reply filed on 01/22/2026 is acknowledged.
However, upon further consideration, the restriction requirement of 12/23/2025 is withdrawn. Thus, claims 1-20 are pending and are under examination.
Priority
This application claims priority to U.S. provisional applications No. 63/398,085 filed on 08/15/2022 and No. 63/299,315 filed on 01/13/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/28/2023 and 01/22/2026 have been received. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner and all references are considered except where they were lined through.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show molecular weight of the ladder and the bands in lanes 1 to 5 of Figure 29 as described in the specification. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). 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. The objection to the drawings will not be held in abeyance.
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 8 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.
Regarding claim 8, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 9, 12-14, 15-16, 17 and 19 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Gonçalves et al. (US 9,487,773 B2).
Regarding claim 1, Gonçalves teaches a screening method (Column 17, lines 7-8, lines 23-33).
Gonçalves teaches detecting the presence and/or level of expression of a reporter molecule in a single, isolated genetically engineered cell (Column 47, lines 15-20).
Gonçalves teaches that the cell presents a cell surface protein (Abstract; column 3, lines 10-27 and lines 28-55)
Gonçalves teaches that the cell is engineered to secrete a heterologous test polypeptide (Column 23, lines 46-52; column 24, lines 5-13).
Gonçalves teaches that the cell is engineered to express a reporter molecule if the test polypeptide activates the cell surface protein (Column 47, lines 15-20).
Regarding claim 2, Gonçalves teaches that the cell comprises a mammalian cell (Column 24, lines 16-21).
Regarding claim 3, Gonçalves teaches a receptor that binds to a human tumor necrosis factor alpha (hTNF-α) which is an endogenous ligand in the body (Column 20, lines 42-48).
Regarding claim 4, Gonçalves teaches that the cell is engineered to express the cell surface protein (Abstract; column 2, lines 46-62)
Regarding claim 5, Gonçalves teaches that the cell surface protein comprises a heterologous receptor (Column 23, lines 46-52).
Regarding claim 8, Gonçalves teaches that the single isolated genetically engineered cell is a well of a multi-well plate (Column 49, lines 20-22).
Regarding claim 9, Gonçalves teaches that the reporter molecule comprises a fluorescent marker, an enzyme, a tagged protein, or a nucleic acid sequence (Column 47, lines 15-20).
Regarding claim 11, Gonçalves teaches that the heterologous test peptide comprises a variant of the cell surface receptor's ligand (Column 4, lines 9-24; column 14, lines 61-65).
Regarding claim 12, Gonçalves teaches that the test polypeptide comprises an antibody or antibody-derived format, a nanobody, VHH, or antigen binding fragment thereof (Abstract; column 2, lines 30-57).
Regarding claim 13, Gonçalves teaches a composition, kit, or system, comprising the genetically engineered cell of claim 1 (Column 41, lines 44-52).
Regarding claim 14, Gonçalves teaches a screening method (Column 17, lines 7-8, lines 23-33). Gonçalves teaches contacting a single, isolated, genetically engineered cell with a test reagent (Column 20, lines 42-58). Gonçalves teaches that the cell presents a cell surface protein (Abstract; column 3, lines 10-27 and lines 28-55). Gonçalves teaches that the cell is engineered to secrete a heterologous test polypeptide (Column 23, lines 46-52; column 24, lines 5-13). Gonçalves teaches that the cell is engineered to express a reporter molecule if one of the test polypeptide or the test reagent activates the cell surface protein (Column 47, lines 15-20). Gonçalves teaches detecting the presence and/or level of expression of the reporter molecule (Column 17, lines 46-52; column 47, lines 15-20)
Regarding claim 15, Gonçalves teaches that the test polypeptide comprises a variant of a cell surface protein ligand (Column 4, lines 9-24; column 14, lines 61-65). Gonçalves teaches that the test reagent comprises an antagonist of receptor activation by the wild-type ligand (Column 20, lines 42-58).
Regarding claim 16, Gonçalves teaches that the test reagent comprises a cell surface protein ligand (Column 4, lines 49-64; “…introducing into the cell a binding molecule which specifically binds either the receptor protein”). Gonçalves teaches that the test polypeptide is derived from a library of potential agonists or antagonists of receptor activation by the ligand (Column 4, lines 9-24, “… The diversified binding molecule, antibody, or library thereof … be used in the inventive selection methods described herein so as to select and identify a binding molecule, or a member of a library of binding molecules, having potentially improved or optimal binding of and/or activity toward a target molecule, such as a receptor protein expressed on the cell surface …”)
Regarding claim 17, Gonçalves teaches a screening method (Column 17, lines 7-8, lines 23-33). Gonçalves teaches contacting a single, isolated, genetically engineered cell with a test reagent comprising a reporter molecule (Column 17, lines 47-59). Gonçalves teaches that the cell presents a cell surface protein (Column 17, lines 47-48; column 21, “in which a detectably labeled antibody ( or reporter molecule) is used to bind cell surface expressed proteins.”). Gonçalves teaches that the test reagent is capable of binding the cell surface protein presented by the cell, forming a reagent-protein complex (Columns 30, lines 60-67 and column 31, lines 1-23). Gonçalves teaches that the test reagent gains entry into the cell when the reagent-receptor complex is formed (Column 31, lines 7-12). Gonçalves teaches that the cell is engineered to secrete a heterologous test polypeptide (Column 23, lines 46-52; column 24, lines 5-13). Gonçalves teaches detecting the presence and/or level of expression of the reporter molecule in the cells (Column 17, lines 46-52; column 47, lines 15-20).
Regarding claim 19, Gonçalves teaches that the virus is selected from Coronavirus A, B, C, or D, Flavivirus, Herpesvirus, Lentivirus, Influenza A, B, or C (Column 8, lines 8-10).
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 (PHOSITA) 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.
Claims 6-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Gonçalves et al. (US 9,487,773 B2) as applied to claim 1 above, and further in view of Tareen et al. (US 2020/0182884 A1).
Regarding claims 6-7 and 10, Gonçalves teaches all of the limitations of the claims as discussed above but fails to teach the following limitations.
Regarding claim 6, Gonçalves does not teach that the secretion of the test polypeptide is constitutive. Regarding claim 7, Gonçalves does not teach that the secretion of the test polypeptide is inducible. Regarding claim 10, Gonçalves does not teach that the method further comprises sequencing the nucleic acids encoding the heterologous test polypeptide.
Regarding claim 6, Tareen teaches that the secretion of the test polypeptide is constitutive ([0164], “MHC class II molecules are constitutively expressed on antigen-presenting cells (APCs), such
as dendritic cells, macrophages or B cells”).
Regarding claim 7, Tareen teaches that the secretion of the test polypeptide is inducible ([0167], “In some embodiments, cells … be induced to express an MHC class II molecule”).
Regarding claim 10, Tareen teaches that the method further comprises sequencing the nucleic acids encoding the heterologous test polypeptide [0217].
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the expression modes of Tareen with the screening method of Gonçalves to generate therapeutic antibodies and peptides because Tareen teaches identifying peptides of an MHC class II molecule for therapeutic purposes (Abstract) and sequencing the identified peptides [0217]. Gonçalves further teaches how to screen for antibodies for therapeutic purposes (Column 20, lines 42-62). A skilled artisan would have been motivated to combine the above inventions to increase the efficiency of screening for therapeutic antibodies. A PHOSITA would have a reasonable expectation of success in combining the methods of Tareen and Gonçalves based on the methods being in the field of detecting the binding of a target to its binding agent. Consequently, it would have been obvious for a PHOSITA to combine the expression modes of Tareen with the screening method of Gonçalves to increase the identification rate of an antibody and to optimize the identification process of a therapeutic antibody.
Claims 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Gonçalves et al. (US 9,487,773 B2) as applied to claim 17 above, and further in view of Hoffmann et al. (Cell 181, 271–280, April 16, 2020, Elsevier Inc.).
Regarding claims 18 and 20, Gonçalves teaches all of the limitations of the claims as discussed above.
Moreover, regarding claim 18, Gonçalves teaches that the test reagent comprises one or more of a virus, virus-like particle, pseudoviruses, and recombinant viral particle (Column 23, lines 41-45; column 30, lines 22-24).
Regarding claim 18, Gonçalves does not teach that the cell surface protein comprises a component of viral entry into the cell.
Regarding claim 20, Gonçalves does not teach that the virus comprises a SARS-CoV-2 virus,
Gonçalves does not teach that the cell surface protein comprises a human angiotensin-converting enzyme 2 (hACE2).
Regarding claim 18, Hoffmann teaches that cell surface protein of ACE2 comprises a component of SARS-CoV-2 viral entry into the cell (Page 271, Summary).
Regarding claim 20, Hoffmann teaches that the virus comprises a SARS-CoV-2 virus (Page 271, Summary). Hoffmann teaches that the cell surface protein comprises a human angiotensin-converting enzyme 2 (hACE2) (Page 271, Summary; page 273, right column, first paragraph, “antiserum raised against human ACE2 blocked SARS-S- and SARS-2-S- but not VSV-G- or MERS-S-driven entry”; page 275, Figure 3, (A), (B) and (C), “hACE2”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine ACE2 cell surface protein of Hoffmann with the screening method of Gonçalves to generate therapeutic antibodies to coronavirus disease 19 (COVID-19) because Hoffmann teaches that pathogenic SARS-coronavirus 2 (SARS-CoV-2) uses the SARS-CoV receptor ACE2 for entry into the cell and identifies a target for therapeutic intervention (Page 271, summary; page 275, right column, third paragraph). A skilled artisan would have been motivated to combine the above methods to screen for a therapeutic antibody for COVID-19 infection. A PHOSITA would have a reasonable expectation of success in combining the methods of Hoffmann and Gonçalves based on the methods being in the field of detecting the binding of a target to its binding agent. Consequently, it would have been obvious for a PHOSITA to combine cell surface protein of Hoffmann with the screening method of Gonçalves to optimize the identification process of a therapeutic antibody for patients with COVID-19.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 8-9, 11, 13, 18-19, 32, 34, and 36 and of copending Application No. 19/117,910 in view of Gonçalves et al. (US 9,487,773 B2), Tareen et al. (US 2020/0182884 A1) and Hoffmann et al. (Cell 181, 271–280, April 16, 2020, Elsevier Inc.). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 1 pertaining to a screening method by detecting the presence and/or level of expression of a reporter molecule in a single, isolated, genetically engineered cell that presents a cell surface protein and is engineered to secrete a heterologous test polypeptide and express a reporter molecule if the test polypeptide activates the cell surface protein, or express a reporter molecule if the test polypeptide does not activate the cell surface protein, ‘910 teaches a screening method for detecting the presence of binding between a secreted polypeptide and a membrane bound target, wherein the secreted polypeptide or the membrane-bound target comprises a polypeptide sequence derived from an antibody or fragment thereof, wherein the secreted polypeptide and the membrane-bound target are included within a compartment, wherein the compartment includes a single, isolated genetically engineered cell expressing the secreted polypeptide and presenting the membrane bound target, wherein the cell is engineered to secrete the secreted polypeptide, present the membrane bound target, or both, wherein detecting binding between a secreted polypeptide and the membrane-bound target comprises: providing a detection agent, wherein the detection agent binds to the secreted polypeptide, the membrane-bound target, or both, and wherein the detection agent does not enter the cell (See claims 1 and 9 of ‘910).
Regarding claim 4 pertaining to that the cell is engineered to express the cell surface protein, ‘910 teaches that the cell is engineered to secrete the secreted polypeptide, present the
membrane bound target, or both (See claims 1 and 34 of ‘910).
Regarding claim 5 pertaining to that the cell surface protein comprises a heterologous receptor, ‘910 teaches that the cell surface protein comprises a heterologous receptor (See claims 1 and 18-19 of ‘910).
Regarding claim 8 pertaining to that the single, isolated, genetically engineered cell is in a well of a multi-well plate, a chamber of a microchip, a microfluid droplet, such as an emulsion droplet, a Nanopen™, ‘910 teaches that the compartment includes a single, isolated genetically engineered cell
expressing the secreted polypeptide and presenting the membrane bound target and that the compartment is a well, a droplet, spatially separated cell culture condition, or an encapsulation (See claims 1 and 8 of ‘910).
Regarding claim 9 pertaining to that the reporter molecule comprises a fluorescent marker, an enzyme, a tagged protein, or a nucleic acid sequence, ‘910 teaches that the reporter molecule
comprises one or more of a nucleic acid barcode, a dye, a fluorescent molecule, an enzyme, a chemical, a protein, a polypeptide tag (See claim 5 of ‘910).
Regarding claim 12 pertaining to that the test polypeptide comprises an antibody or antibody-derived format, a nanobody, VHH, or antigen binding fragment thereof, ‘910 teaches that the secreted polypeptide or the membrane-bound target comprises a polypeptide sequence derived from an antibody or fragment thereof (See claims 1 and 32 of ‘910).
Regarding claim 13 pertaining to a composition, kit, or system, comprising the genetically engineered cell of claim 1, ‘910 teaches a kit that comprise a cell containing the nucleic acid sequence encoding the membrane-bound target, and optionally, wherein the nucleic acid encoding the secreted polypeptide and the nucleic acid encoding the membrane-bound target are present on a same construct (See claim 36 of ‘910).
Regarding claim 14 pertaining to a screening method by contacting a single, isolated, genetically engineered cell with a test reagent wherein the cell present a cell surface protein and is engineered to secrete a heterologous test polypeptide and express a reporter molecule if one of the test polypeptide or the test reagent activates the cell surface protein and detecting the presence and/or level of expression of the reporter molecule, ‘910 teaches a screening method for detecting the presence of binding between a secreted polypeptide and a membrane bound target, wherein the secreted polypeptide or the membrane-bound target comprises a polypeptide sequence derived from an antibody or fragment thereof, wherein the secreted polypeptide and the membrane-bound target are included within a compartment, wherein the compartment includes a single, isolated genetically engineered cell expressing the secreted polypeptide and presenting the membrane bound target, wherein the cell is engineered to secrete the secreted polypeptide, present the membrane bound target, or both, wherein detecting binding between a secreted polypeptide and the membrane-bound
target comprises: providing a detection agent, wherein the detection agent binds to the secreted polypeptide, the membrane-bound target, or both, and wherein the detection agent does not enter the cell (See claims 1 and 9 of ‘910).
Regarding claim 16 pertaining to that the test reagent comprises a cell surface protein ligand, and wherein the test polypeptide is derived from a library of potential agonists or antagonists of receptor activation by the ligand, ‘910 teaches that before or contemporaneous with the detection step, generating a collection of genetically engineered cells, wherein each of the genetically engineered cells comprises a gene encoding a membrane-bound polypeptide of a library of membrane-bound polypeptides and a gene encoding a secreted polypeptide from a library of secreted polypeptides (See claims 11, 13 of ‘910).
Regarding claim 17 pertaining to a screening method by contacting a single, isolated, genetically engineered cell with a test reagent comprising a reporter molecule, wherein the cell presents a cell surface protein, wherein the test reagent is capable of binding the cell surface protein presented by
the cell, forming a reagent-protein complex, and wherein the test reagent gains
entry into the cell when the reagent-receptor complex is formed, wherein the cell is engineered to secrete a heterologous test polypeptide, and detecting the presence and/or level of expression of the reporter molecule in the cells, ‘910 teaches that a screening method for detecting the presence of binding between a secreted polypeptide and a membrane bound target, wherein the secreted polypeptide or the membrane-bound target comprises a polypeptide sequence derived from an antibody or fragment thereof, wherein the secreted polypeptide and the membrane-bound target are included within a compartment, wherein the compartment includes a single, isolated genetically engineered cell expressing the secreted polypeptide and presenting the membrane bound target, wherein the cell is engineered to secrete the secreted polypeptide, present the membrane bound target, or both, wherein detecting binding between a secreted polypeptide and the membrane-bound
target comprises: providing a detection agent, wherein the detection agent binds to the secreted polypeptide, the membrane-bound target, or both, and wherein the detection agent does not enter the cell (See claims 1 and 9 of ‘910).
Regarding claim 2 pertaining to that the cell comprises a mammalian cell, an insect cell, an avian cell, a yeast cell, a fungal cell, a plant cell, or a bacterial cell, ‘910 does not teach that the cell comprises a mammalian cell, an insect cell, an avian cell, a yeast cell, a fungal cell, a plant cell, or a bacterial cell.
Regarding claim 3 pertaining to that the cell surface protein comprises an endogenous receptor, ‘910 does not teach that the cell surface protein comprises an endogenous receptor.
Regarding claim 6 pertaining to that the secretion of the test polypeptide is constitutive, ‘910 does not teach that the secretion of the test polypeptide is constitutive.
Regarding claim 7 pertaining to that the secretion of the test polypeptide is inducible, ‘910 ‘910 does not teach that the secretion of the test polypeptide is inducible.
Regarding claim 10 pertaining to that the method further comprises sequencing the nucleic acids encoding the heterologous test polypeptide, ‘910 does not teach sequencing the nucleic acids encoding the heterologous test polypeptide.
Regarding claim 11 pertaining to that the heterologous test peptide comprises a variant of the cell surface receptor's ligand, ‘910 does not teach that that the heterologous test peptide comprises a variant of the cell surface receptor's ligand.
Regarding claim 15 pertaining to that the test polypeptide comprises a variant of a cell surface protein ligand, and wherein the test reagent comprises an agonist or an antagonist of receptor activation by the wild-type ligand, ‘910 does not teaches that the test polypeptide comprises a variant of a cell surface protein ligand, and wherein the test reagent comprises an agonist or an antagonist of
receptor activation by the wild-type ligand.
Regarding claim 16, ‘910 does not teach that the test polypeptide is derived from a library of potential agonists or antagonists of receptor activation by the ligand.
Regarding claim 17, ‘910 does not teach wherein the test reagent gains entry into the cell when the reagent-receptor complex is formed.
Regarding claim 18 pertaining to that the test reagent comprises one or more of a
virus, virus-like particle, pseudoviruses, and recombinant viral particle, and wherein the cell
surface protein comprises a component of viral entry into the cell, ‘910 does not teach that the test reagent comprises one or more of a virus, virus-like particle, pseudoviruses, and recombinant viral particle, and wherein the cell surface protein comprises a component of viral entry into the cell.
Regarding claim 19 pertaining to that the virus is selected from Coronavirus A, B,
C, or D, Flavivirus, Herpesvirus, Lentivirus, Influenza A, B, or C, ‘910 does not teach that the virus is selected from Coronavirus A, B, C, or D, Flavivirus, Herpesvirus, Lentivirus, Influenza A, B, or C.
Regarding claim 20 pertaining to that the virus comprises a SARS-CoV-2 virus, and wherein the cell surface protein comprises a human angiotensin-converting enzyme 2 (hACE2), ‘910 does not teach that the virus comprises a SARS-CoV-2 virus, and wherein the cell surface protein comprises a human angiotensin-converting enzyme 2 (hACE2).
Regarding claim 2, Gonçalves teaches that the cell comprises a mammalian cell (Column 24, lines 16-21).
Regarding claim 3, Gonçalves teaches that the cell surface protein comprises an endogenous receptor (Abstract; column 2, lines 46-62).
Regarding claim 11, Gonçalves teaches that the heterologous test peptide comprises a variant of the cell surface receptor's ligand (Column 4, lines 9-24; column 14, lines 61-65).
Regarding claim 15, Gonçalves teaches that the test polypeptide comprises a variant of a cell surface protein ligand (Column 4, lines 9-24; column 14, lines 61-65).
Gonçalves teaches that the test reagent comprises an antagonist of receptor activation by the wild-type ligand (Column 20, lines 42-58).
Regarding claim 16, Gonçalves teaches that the test polypeptide is derived from a library of potential agonists or antagonists of receptor activation by the ligand (Column 4, lines 9-24, “… The diversified binding molecule, antibody, or library thereof … be used in the inventive selection methods described herein so as to select and identify a binding molecule, or a member of a library of binding molecules, having potentially improved or optimal binding of and/or activity toward a target molecule, such as a receptor protein expressed on the cell surface …”).
Regarding claim 17, Gonçalves teaches that the test reagent is capable of binding the cell surface protein presented by the cell, forming a reagent-protein complex (Columns 30, lines 60-67 and column 31, lines 1-23).
Gonçalves teaches that the test reagent gains entry into the cell when the reagent-receptor complex is formed (Column 31, lines 7-12).
Regarding claim 18, Gonçalves teaches that the test reagent comprises one or more of a virus, virus-like particle, pseudoviruses, and recombinant viral particle (Column 23, lines 41-45; column 30, lines 22-24).
Regarding claim 19, Gonçalves teaches that the virus is Lentivirus(Column 8, lines 8-10).
Regarding claim 6, Tareen teaches that the secretion of the test polypeptide is constitutive ([0164], “MHC class II molecules are constitutively expressed on antigen-presenting cells (APCs), such
as dendritic cells, macrophages or B cells”).
Regarding claim 7, Tareen teaches that the secretion of the test polypeptide is inducible ([0167], “In some embodiments, cells … be induced to express an MHC class II molecule”).
Regarding claim 10, Tareen teaches that the method further comprises sequencing the nucleic acids encoding the heterologous test polypeptide [0217].
Regarding claim 18, Hoffmann teaches that cell surface protein of ACE2 comprises a component of SARS-CoV-2 viral entry into the cell (Page 271, Summary).
Regarding claim 20, Hoffmann teaches that the virus comprises a SARS-CoV-2 virus (Page 271, Summary). Hoffmann teaches that the cell surface protein comprises a human angiotensin-converting enzyme 2 (hACE2) (Page 271, Summary; page 273, right column, first paragraph, “antiserum raised against human ACE2 blocked SARS-S- and SARS-2-S- but not VSV-G- or MERS-S-driven entry”; page 275, Figure 3, (A), (B) and (C), “hACE2”).
It would have been obvious to one of ordinary skill in the art before the filing date of the application to combine the mammalian cell system of Gonçalves with the screening method of ‘910 because Gonçalves noted that mammalian cell display platforms offer an advantage over phage-display in that fluorescence activated cell sorting (FACS) is coupled with cell surface antibody display to allow monitoring of both antibody expression on the cell surface and the ability of that antibody to bind to its target (Column 1, lines 59-64). A skilled artisan would have been motivated to combine the expression modes of Tareen with the combined methods of Gonçalves and ‘910 because Tareen teaches identifying peptides of an MHC class II molecule for therapeutic purposes (Abstract) and sequencing the identified peptides [0217]. A skilled artisan would have been further motivated to combine the ACE2 cell surface protein of Hoffmann with the combined methods of Tareen, Gonçalves and ‘910 because Hoffmann teaches that pathogenic SARS-coronavirus 2 (SARS-CoV-2) uses the SARS-CoV receptor ACE2 for entry into the cell and identifies a target for therapeutic intervention (Page 271, summary; page 275, right column, third paragraph). The ordinary artisan would have been motivated to use the SARS-CoV receptor ACE2 in the screening method of ‘910 to identify an antibody for treating a patient for COVID-19. Therefore, such combinations would be considered an advantageous additives to ‘910 which also recognizes a need for improving screening methods.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OMAR RAMADAN whose telephone number is (571)270-0754. The examiner can normally be reached Monday-Friday 8:30 am - 5:00 pm.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 February 23, 2026