DETAILED ACTION
Non-Final Rejection
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I claims 1-4 and 8-9 in the reply filed on 06/23/2026 is acknowledged.
Status of Claims
3. Claims 1-9 as filed on 12/19/2023 are pending.
4. Claims 5-7 are withdrawn from examination being directed to the non-elected invention.
5. Claims 1-4 and 8-9 are under examination.
Priority
6. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. JP2021-084987, filed on
05/20/2021. The instant application 18/562,099 is 371 of PCT/JP2022/0209 with a filing date 05/20/2022.
Information Disclosure Statement
7. The information disclosure statement (IDS) submitted on 10/10/2024, 03/10/2025, and 04/09/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
8. The use of the terms Tween™ on page 10; Perfect-Block™ on pages 10 and 13; Nunc-Immuno™ Module F8 Maxisorp Surface™ on pages 10 and 12; and possibly others in the specification, which are trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, ℠, or ® following the terms. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Applicants are required to properly annotate all trade names and/or marks that are present in the specification.
9. The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which Applicant may become aware in the specification.
10. No drawings were present at the time of this Office Action.
Claim Rejections - 35 USC § 112
11. 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 1 and 3 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 recite “utilizing” the antigen-antibody reaction in line 1 of the claim. The claims recite a use without any active steps delineating how the use is actually practiced. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986) and MPEP § 2173.05(q). Therefore, it is unclear if the claim is intended to be drawn to a product, i.e., the immunoassay or the immunoassay as a kit, or drawn to a method of using the immunoassay. The presence of multiple very different interpretations of the same claim language renders the claim indefinite.
Claim 3 recite “composed of the amino acid sequences of one of SEQ ID NOs:1 to 4.”, wherein 1, 2, 3 and 4 are the different sequence numbers. It is unclear if this transitional phrase is open-ended or close-ended. In other words, it is unclear if any additional, unrecited elements not specified in the claim are included or excluded. The presence of multiple very different interpretations of the same claim language renders the claim indefinite. It is recommended that the “composed of” limitation be amended to a proper transitional phrase, i.e., “comprising”, “consisting of”, or “consisting essentially of”. In the interest of compact prosecution, the transitional phrase “composed of” has been interpreted in the same manner as “consisting of”. See AFG Industries, Inc. v. Cardinal IG Company, 239 F.3d 1239, 1245, 57 USPQ2d 1776, 1780-81 (Fed. Cir. 2001); In re Bertsch, 132 F.2d 1014, 1019-20, 56 USPQ 379, 384 (CCPA 1942); and MPEP § 2111.03.
Claim Rejections - 35 USC § 112 (a) Written Description
12. 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 1-4 and 8-9 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.
Claims 1-4 and 8-9 are drawn to an antibody, which encompasses a monoclonal antibody, that binds to or that recognizes the shell domain of the norovirus capsid. At a minimum, at least six of the parental CDRs that could define an antibody genus with this claimed function of binding or recognizing must be defined. However, no such CDRs are taught by the claims, leading one to turn to the instant disclosure. The instant specification para [0017] of the instant disclosure teaches that the anti-norovirus antibody undergoes an antigen-antibody reaction with the peptides composed of SEQ ID NOs: 1, 2, 3 and 4 and binds to an epitope in the shell domain of the norovirus capsid protein (VP1). There is no recitation for the sequence of even one parental monoclonal antibody CDR in the instant disclosure. The closest teaching of the antibody occurs in para [0024], wherein hybridoma cells are cultured according to conventional methods to obtain a monoclonal antibody that is, in turn, propagated in a mammal (see para [0035]. It is further taught by the instant disclosure that noroviruses are rich in genetic diversity and classified into five groups based on sequence similarity of capsid genes (para [0035], [0040]). In general, this creates an enormous breadth of potential antibody or monoclonal antibody sequences with the six parental CDRs for a single norovirus that becomes innumerable when coupled with the massive genera of sequences for the five different groups of noroviruses.
When there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The claims are drawn to several genera, i.e., norovirus groups, which are each comprised of innumerable sequences, yet, the specification has only adequately described, and successfully reduced to practice, four generic anti-norovirus shell domain recognizing monoclonal antibodies that bind to the desired epitope without disclosing any structural or functional limitations of the monoclonal antibodies themselves (paragraphs 0045 – 0050, Table 1). The disclosed four monoclonal antibodies are not representative of the extremely large genus of monoclonal antibodies. One of ordinary skills in the art cannot conclude that Applicant was in possession of the innumerable monoclonal antibodies or antibodies encompassed by the disclosed genera. Absent the disclosed antigen sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, each individual sequence utilized for the antibody. Thus, it is clear that the breadth of the recited genera in the claims far overreaches the Applicant’s contribution.
In the absence of a representative number of examples, the specification must at least describe the structural features that are required for the claim function. In the instant case, the specification should explain the structure of the antibody that is required to bind to the defined epitopes, namely the CDRs. However, the specification fails to describe any substantive structural limitations as to establish the criteria necessary to design an antibody against norovirus that binds to the shell epitopes and has all six parental CDRs.
The disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011) (patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties). Describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). See MPEP 216.
In the context of claimed invention, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Amgen court expressly stated that the so-called "newly characterized antigen" test should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Id.
Thus, while Applicant has generically described the antigen the claimed antibody is supposed to bind, no specific properties of the claimed antibody have been adequately described. The claims encompass millions of antibody structures that cannot be visualized from the prior art or instant disclosure. One having ordinary skill in art cannot determine the structures encompassed by the claimed genera. The species described are too generic and cannot be considered representative of the entire recited genus. No parental CDRs have been described in the claims or instant disclosure. Overall, the claims as currently written are not adequately described and one of ordinary skills in that art would readily appreciate that Applicant was not in possession of the claimed genera, i.e., an anti-norovirus antibody that binds to the disclosed epitopes of SEQ ID NOs: 1- 4, at the time of filing.
"The purpose of [the written description requirement] is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification"); LizardTech Inc. v. Earth Resource Mapping Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). This requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement for a claimed genus, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. See In re Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345, 54 USPQ2d 1915, 1917 (Fed. Cir. 2000). “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” See In re Enzo Biochem, Inc. v. Gen–Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). See also MPEP § 2163.
The written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See In re University of California v. Eli Lilly & Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997); and Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, the applicant must describe a sufficient variety of species to reflect the variation within the genus. See In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See In re Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." See In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. This is because functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.” The description needed to satisfy the written description varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. See In re University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014); In re Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010); and In re Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.
Due to the variation among antibodies with respect to their CDRs, the structure of which is what correlates with their function, it is very difficult to provide adequate representation, i.e., written description, of a functionally defined antibody genus. For example, it is highly unlikely that any CDR structure will be shared by an entire genus. Additionally, the disclosure of one set of antibody CDRs does not guide one of skill in the art to the next set of CDRs. That is to say that all CDRs are unique and none are obvious. This is because it is well known in the art that the mutation of even a single CDR residue can dramatically impact antibody function and even lead to the loss of antigen binding. For example, it is taught by Rudikoff, S., et. al., (Single amino acid substitution altering antigen-binding specificity. Proceedings of the National Academy of Sciences of the United States of America, 79(6), 1979–1983; Published 03/1982) that the mutation of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding specificity (page 1979, title and abstract). Thus, while Applicant has described one or more species within each of the genera recited, and the art may provide more, each genus is very large and would encompass antibody structures, i.e., CDR sets, that cannot be visualized from the prior art or instant disclosure. One with skill in the art cannot determine the antibody structures encompassed by the claimed genera as they are only defined by their function. Any future antibody structure may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Therefore, the antibody or monoclonal antibody species described in prior art or four species of the monoclonal antibody in the instant specification (para [0045] Table 1) cannot be considered representative of the recited genera of monoclonal antibodies. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
35 USC § 112(a) – Scope of Enablement
13. Claims 1-4 and 8-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the disclosed and tested four monoclonal antibodies (instant specification para [0045], Table 1) and fragments thereof that have a full set of parental CDRs, does not reasonably provide enablement for merely any antigen-binding fragment, which reads on having as little as one CDR. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit has developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors, to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." The factors considered include, but are not limited to: (A) the breadth of the claims; (B) the nature of the invention; (C) the state of the prior art; (D) the level of one of ordinary skill in the art; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims and nature of the invention: Claims 1-4 and 8-9 of the claimed invention are drawn to an immunoassay comprising interaction of anti-norovirus shell protein domain antibody, or an antigen-binding fragment thereof, that binds to an antigen with SEQ ID NOs: 1-4. Further limitations include that the antibody be a monoclonal antibody, as disclosed in claims 2-4 and 8-9.
The level of one of ordinary skill in the art: The required level of skills in art is that of Ph.D. level scientists and medical doctors (D.O. and/or M.D.).
Amount of direction and existence of working examples: The instant application teaches a single working example with four generic monoclonal antibodies, which does not represent an example for any antigen-bind fragment, which could be numerous CDRs or as little as one CDR.
Working Example: The closest working example is in paragraphs [0035]- [0053]. It is taught that mice are immunized with norovirus virus-like particles (VLPs), then cells were fused with mouse myeloma cells to yield hybridomas. The hybridoma cells are cultured according to conventional methods to obtain a monoclonal antibody that is, in turn, propagated in mice. This resulted in cell lines that produce anti-norovirus monoclonal antibodies, wherein four antibodies directed to the shell domain of norovirus, i.e., SMoAb1 and SMoAb2, were found to recognize SEQ ID NOs: 1 and 3, respectively and SMoAb3and SMoAb4 were found to recognize SEQ ID NOs: 2 and 4, respectively. Aside from the four antibodies disclosed, there is no guidance as to what CDRs are required to bind to the defined epitopes. The instant disclosure offers no reasonable guidance or direction to use any antigen-binding fragments.
State of the prior art and unpredictability in the art: It is taught by Paul, W. E., (Fv structure and diversity in three dimensions, Fundamental Immunology, 3, 292-295; Published 1993), hereby Paul, that an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody (page 293, left column, lines 3 – 8; right column, lines 1 – 9 and 27 – 30). It is further taught that both the heavy and light chain variable regions are comprised of three CDRs or hypervariable regions, for a total of six CDRs per antibody, which provide the majority of the contact residues for the binding of the antibody to its target epitope (page 293, left column lines 3 – 8 and 19 – 22). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin (page 293, left column, lines 8 – 22). It is expected that all of the heavy and light chain CDRs are required in their proper order in the context of framework sequences which maintain their required conformation in order to produce a protein having antigen-binding function. Moreover, the proper association of the CDRs for both the heavy and light chain variable regions is required in order to form functional antigen-binding sites.
It is further taught by Bendig M. M., (Methods: A Companion to Methods in Enzymology, 8, 83-93; Published 1995), hereby Bendig, teaches that the general strategy for “humanizing” antibodies involves the substitution of all six CDRs from a rodent antibody and grafting these regions into human regions (page 83, abstract and right column, second paragraph; page 84). It is noted that Bendig used Kabat CDRs in their humanization process (page 86, right column, second paragraph). Bendig goes on to teach that the six CDRs of the antibody’s light and heavy chain variable regions form loop-like structures that make direct contact with the antigen, holding it in place (page 84, figure 3).
Quantity of experimentation needed: At a minimum, the art teaches that a skilled artisan would consider the predictive function of an antibody if the six CDRs are defined, wherein there are three each for the heavy and light chain variable regions, in the context of the framework sequences with the correct spatial orientation. Thus, one of skill in the art would neither expect nor predict the appropriate function of any antigen-binding fragment of the instant claims for an anti-norovirus antibody as broadly as claimed, as such a fragment could have as little as one CDR antibody and, thus, would not provide the framework required to bind to the disclosed antigen.
Any and all enablement of the claimed fragments must therefore come from the instant disclosure. However, the instant disclosure only teaches the production and usage of four generic anti-norovirus shell domain monoclonal antibodies that bind to the desired epitope. The claims are clearly not enabled to their full scope. Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies or antibody fragments not having all of the relevant functional CDRs in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. Claims that contain materials demonstrated not to bind to the critical element of the invention are also not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
For the reasons discussed above, undue experimentation is required to practice
the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. It would take undue trials and errors to practice the claimed invention in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims.
Therefore, the instant disclosure is not enabled for any antigen-binding fragment as presently written, but rather the instant disclosed and tested antibodies and fragments thereof that have a full set of parental CDRs that binds to the disclosed antigen sequences. Thus, any claim that does not further limit the “an antigen-binding fragment” as presently written to an antibody is not enabled. This includes elected claims 1-4 and 8-9. It is recommended that all iterations of “an antigen-binding fragment thereof” be removed.
35 USC § 112(a) – Budapest Treaty Requirement for Deposit of Biological Materials.
14. Claims 1-4, and 8-9 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 enablement requirement.
This is a Budapest Treaty based Requirement for Deposit of Biological Materials.
Claims 1-4, and 8-9 contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claim 1-4 and 8-9 requires antibody or monoclonal antibody for the invention of an immunoassay of norovirus utilizing the antigen-antibody reaction between norovirus in a sample and an antibody or an antigen-binding fragment thereof that recognizes the shell domain of the norovirus capsid.
As a required elements the antibody or monoclonal antibody, it must be known and readily available to the public or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the enablement requirements of 35 U.S.C. § 112, first paragraph, may be satisfied by a deposit of the claimed antibody/monoclonal antibody or more specifically the hybridoma cell clone producing the claimed monoclonal antibody. See 37 CFR 1.802. One cannot practice the claimed invention without the claimed antibody or monoclonal antibody. Therefore, access to the claimed monoclonal antibody is required to practice the invention. The specification does not provide a repeatable method for readily obtaining or producing the claimed antibody without access to the claimed antibody and it does not appear to be a readily available material. The production of monoclonal antibodies by hybridoma technology, although is known in the art, the probability of obtaining the desired monoclonal antibodies is uncertain and production of monoclonal antibodies by hybridoma technology and selection of hybridoma clones producing monoclonal antibodies binding or recognizing to specific epitopes or regions of the shell domain of the norovirus capsid is a laborious process.
Deposit of the claimed antibody or more specifically the hybridoma cell clones producing the claimed monoclonal antibody in a recognized deposit facility would satisfy the enablement requirements of 35 U.S.C. 112, because the claimed antibody would be readily available to the public to practice the invention claimed, see 37 CFR 1.801- 37 CFR 1.809.
If the deposit was made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by applicants, or a statement by an attorney of record over his or her signature and registration number, or someone empowered to make such a statement, stating that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of the patent, would satisfy the deposit requirement.
If the deposit was not made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 CRF 1.801-1.809 and MPEP 2402-2411.05, applicants may provide assurance of compliance by statement, affidavit or declaration or by someone empowered to make the same or by a statement by an attorney of record over his or her signature and registration number showing that:
(a) during the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the enforceable life of the patent, whichever is longer;
(d) a test of the viability of the biological material at the time of deposit (see 37 CFR 1.807); and
(e) the deposit will be replaced if it should ever become inviable.
In addition, the identifying information set forth in 37 CFR 1.809(d) should be added to the specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
Thus, claims 1-4 and 8-9 lack written description for the claimed genus of antibody or monoclonal antibody that is free of prior art. Since the antibody or monoclonal antibody claims the binding or recognizes the shell domain of the norovirus capsid SEQ ID NOs: 1-4, it is necessary for the artisan to be able to use it in the claimed immunoassay. The claims 1-4 and 8-9 are not enabled for the full scope of the use of the claimed four antibodies are not enabled for use because the antibodies or monoclonal antibodies or hybridoma cell clone producing monoclonal antibody does not comply with deposit requirement as recited supra.
Claim Interpretation
15. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1. Instant claim 1 is interpreted to be directed an immunoassay of norovirus utilizing the antigen-antibody reaction between norovirus in a sample and an antibody or an antigen-binding fragment thereof that recognizes the shell domain of the norovirus capsid. Under BRI the antibody is interpreted to be a mammalian polyclonal antibody or monoclonal antibody derived from mouse or other species (instant specification para [0016]-[0017], [0044]). The immunoassay is not limited to a specific method and any well-known immunoassay, such as sandwich assay, immune-agglutination assay, immunochromatography or competitive assay (instant specification para [0029]).
Claim 3. The instant claim 3 is interpreted to be directed to an immunoassay comprising a monoclonal antibody or an antigen-binding fragment thereof undergoes antigen-antibody reaction with a peptide composed of the conserved amino acid sequence of one of SEQ ID NOs:1 to 4.
Claim Rejections - 35 USC § 102
16. 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.
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.
Claims 1-2, 4 and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al 2021 (BMC Microbiol. 2021 Jan 11; 21:22).
Claims 1-2, 4 and 8-9: Xu et al 2021 is in the art and anticipated instant claims 1-2, 4 and 8-9 by disclosing an immunochromatographic assay (ICA) (reads on an immunoassay) developed for effective detection of Human noroviruses (HuNoVs) in clinical samples. Monoclonal antibodies (MAbs) against the shell (S) domain in the major capsid protein of HuNoVs were used in the ICA assay. The limit of detection for HuNoVs in clinical samples were 1.2 × 106 genomic copies per gram of stool sample (gc/g) and 4.4 × 105 gc/g for genogroup I and II (GI and GII) HuNoVs, respectively. A total of 122 clinical samples were tested for HuNoVs by the ICA and compared against RT-qPCR. No cross-reaction with other common enteric viruses or bacteria was observed. The ICA detected a broad range of HuNoVs genotypes, including GI.1, GI.3, GI.4, GI.6, GI.14, GII.2, GII.3, GII.4, GII.6, GII.13, and GII.17. Xu et al 2021 demonstrated that ICA targeting the S domain of VP1 effectively identified the different genotypes of HuNoVs in clinical samples with high sensitivity and specificity (See, abstract, Figs 1-3, Tables 1-3, entire article).
Claim Rejections - 35 USC § 103
17. 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.
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.
Claim 1-4 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al 2021 (BMC Microbiol. 2021 Jan 11; 21:22), and further in view of Ko Gwang Pyo et al 2010 (KR2010048974A, 05/11/2010) and Parra et al 2013 (PLoS one, 8(6), e67592).
Claims 1-2, 4 and 8-9: The disclosures Xu et al 2021 that taught claims 1-2, 4 and 8-9 as recited supra under 35 U.S.C. 102(a)(1) are incorporated here in entirety to render obvious claims 1-2, 4 and 8-9.
Claim 3: Xu et al 2021 do not teach instant claim 3 limitation, wherein the monoclonal antibody or an antigen-binding fragment thereof undergoes antigen-antibody reaction with a peptide composed of the amino acid sequence of one of SEQ ID NOs:1 to 4.
Ko Gwang Pyo et al 2010 teaches a method of detecting norovirus comprising a novel norovirus monoclonal antibody that binds to the antigen epitope of the capsid protein of a norovirus, the antigen epitope amino acid sequence has 100% identity with instant SEQ ID NO: 2 as recited below:
Query Match 100.0%; Score 113; Length 100;
Best Local Similarity 100.0%;
Matches 22; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PVAGASTAVATAGQVNMIDPWI 22
||||||||||||||||||||||
Db 35 PVAGASTAVATAGQVNMIDPWI 56
Parra et al 2013 is in the art and additionally teaches noroviruses are major pathogens associated with acute gastroenteritis. They are diverse viruses, with at least six genogroups (GI-GVI) and multiple genotypes defined by differences in the major capsid protein, VP1. This diversity has challenged the development of broadly cross-reactive vaccines as well as efficient detection methods. Parra et al 2013 disclosed the characterization of a broadly cross-reactive monoclonal antibody (MAb) raised against the capsid protein of a GII.3 norovirus
strain. The MAb were assessed using an Enzyme-linked immunosorbent assay (ELISA) for reactivity with VLPs and denatured VP1 protein from GI, GII, GIV and GV noroviruses, and mapped to a linear epitope located in the inner shell domain. An alignment of all available VP1 sequences showed that the putative epitope (residues 52–56) is highly conserved across the genus Norovirus. This broadly cross-reactive MAb thus constitutes a valuable reagent for the diagnosis using ELISA assay and study of these diverse noroviruses (See, abstract, Fig 1 and legends, methods, entire article).
It would have been obvious to one of ordinary skill in the art to modify the prior art teachings of Xu et al 2021 with additional express teachings of Ko Gwang Pyo et al 2010 and Parra et al 2013 importance of development of an immunoassay to detect diverse genotypes of norovirus using a monoclonal antibody directed to a conserved epitope in shell domain of VP1 capsid protein to develop an immunoassay to detect and quantify noroviruses in clinical or experimental specimens/samples to arrive at the invention of claims 1-4 and 8-9. One of the ordinary skills in the art would have a reasonable expectation of success given the applied combined prior art teachings to develop the norovirus detection immunoassay using anti-shell MAbs for commercial success. This is analogous to some teaching, suggestions, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the invention as claimed in claims 1-4 and 8-9. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (see MPEP § 2143, example of rationales, A-G).
Conclusion
18. No claim is allowed.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMADHAN J JADHAO whose telephone number is (703)756-1223. The examiner can normally be reached M-F 8:00-5:00.
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/SAMADHAN JAISING JADHAO/ Examiner, Art Unit 1672
/BENNETT M CELSA/ Primary Examiner , Art Unit 1600
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