DETAILED ACTION
Non-Final Rejection
Notice of Pre-AIA or AIA Status
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 1-3 and 6 in the reply filed on 07/20/2026 is acknowledged.
Status of Claims
3. Claims 1-8 as filed on 12/18/2023 are pending.
4. Claims 4-5 and 7-8 are withdrawn being directed to non-elected invention.
5. Claims 1-3 and 6 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. JP2021-084986, filed on
05/20/2021. The instant application 18/562,078 is 371 of PCT/JP2022/020945 with a filing date 05/20/2022.
Information Disclosure Statement
7. The information disclosure statement (IDS) submitted on 10/10/2024, and 07/09/2026 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 11; Perfect-Block™ on pages 11 and 13; 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 Objections
11. Claim 1 is objected to because of the following informalities:
(a) Claim 1 may be re-written for clarity in a format similar to claims 2-3 and 6.
An anti-norovirus antibody or an antigen-binding fragment thereof which undergoes antigen-antibody reaction with the peptides composed of the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.
(b) Claim 1 recite a transitional phrase “composed of” the amino acid sequences of SEQ ID NO:1 and SEQ ID NO: 2, respectively, or an antigen-binding fragment thereof.
It is recommended that the “composed of” limitation be amended to a proper transitional phrase, i.e., “comprising”, “consisting of”, or “consisting essentially of” for purposes of clarity since in light of the specification the scope is unclear.
See MPEP 2111.03 IV (“ … he transitional phrase "composed of" has been interpreted in the same manner as either "consisting of" or "consisting essentially of," depending on the facts of the particular case. See AFG Industries, Inc. v. Cardinal IG Company, 239 F.3d 1239, 1245, 57 USPQ2d 1776, 1780-81 (Fed. Cir. 2001) (based on specification and other evidence, "composed of" interpreted in same manner as "consisting essentially of"); In re Bertsch, 132 F.2d 1014, 1019-20, 56 USPQ 379, 384 (CCPA 1942) ("Composed of" interpreted in same manner as "consisting of"; however, the court further remarked that "the words ‘composed of’ may under certain circumstances be given, in patent law, a broader meaning than ‘consisting of.’"
Appropriate correction is required.
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 1-3 and 6 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 1-3 and 6 are drawn to an antibody, which encompasses a monoclonal antibody, that binds to or that recognizes the peptide composed of the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2, respectively. At a minimum, at least six of the parental CDRs that could define a genus of an antibody with this claimed function of binding or recognizing (antigen-antibody interaction) 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 (binding) with the peptides composed of SEQ ID NOs: 1, and 2, and binds to an epitope in whole or part of the amino acid sequence of SEQ ID NO: 3. There is no recitation for the sequence of even one parental antibody or monoclonal antibody CDR in the instant disclosure. The closest teaching of the antibody occurs in para [0028], [0030], [0039], wherein hybridoma cells are cultured according to conventional methods to obtain a monoclonal antibody that is, in turn, propagated in a mammal (see para [0030]. 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 [0003], [0004]). 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 an antibody or monoclonal antibodies themselves (paragraphs [0049], [0051], [0052, Table 1). The disclosed two 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 genus 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 genus. 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- 2, and SEQ ID NO: 3 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 two species of the monoclonal antibody in the instant specification (para [0049] 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 1-3 and 6 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 two monoclonal antibodies (instant specification para [0049], 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 1-3 and 6 of the claimed invention are drawn to an anti-norovirus antibody comprising an antigen-antibody reaction, or an antigen- antigen-binding fragment thereof reaction ( binds to an antigen) with SEQ ID NOs: 1-2 and 3. Further limitations include that the antibody be a monoclonal antibody, as disclosed in claims 3 and 6.
The level of one of ordinary skills 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 two 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 1 is in paragraphs [0039]- [0059]. 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 two antibodies directed to the shell domain of norovirus, i.e., SMoAb1 and SMoAb2, were found to recognize SEQ ID NOs: 1-2 and 3, respectively. Aside from the two monoclonal antibodies disclosed without a structure, 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 skills 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 and unreasonable 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 1-3 and 6. 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 1-3, and 6 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 1-3, and 6 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.
Claims 1-3 and 6 require 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 1-3 and 6 lack written description for the claimed genus of an antibody or monoclonal antibody that is free of prior art. Since the antibody or monoclonal antibody claims the binding or recognizing the peptides of SEQ ID NOs: 1-2 and 3, it is necessary for the artisan to be able to use it in the claimed immunoassay. The claims 1-3 and 6 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 to an anti-norovirus antibody or an antigen-binding fragment thereof which undergoes antigen-antibody reaction with the peptides composed of the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.
The transitional phrase “composed of” has been interpreted in the same manner as “consisting of”.
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], [0045], [049], Table 1). The antigen-antibody reaction can be assessed by 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 2. The instant claim 2 is interpreted to be directed to the anti-norovirus antibody of claim 1 or an antigen-binding fragment thereof, whose epitope is the whole or a part of the amino acid sequence of SEQ ID NO: 3.
Claims 3 and 6 are interpreted to be directed to the anti-norovirus antibody or an antigen-binding fragment thereof, wherein the anti-norovirus antibody is a monoclonal antibody.
The claimed antibody or a monoclonal antibody is interpreted to be used for development of an immunoassay.
Claim Rejections - 35 USC § 103
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 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.
17: Claims 1-3 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Kageyama et al 2004 (US20040073006A1, 04/15/2004) and further in view of Kageyama et al 2002 (Virology, 2002, 299 (2), 225-239 and attached PDF printout of VP1 protein sequence for Accession YP_009700097), Robilotti et al 2015 (Clin Microbiol Rev. 2015 Jan;28(1):134-64), Richardson et al 2014 (US8841120B2, 09/23/2014), Li et al 2010 (Virus Res. 2010 Aug;151(2):142-7) and Malm et al 2016 (Mol Immunol. 2016 Oct; 78:27-37).
Claims 1-3 and 6: Kageyama et al 2004 is in art and teaches antibodies and monoclonal antibodies against a Norwalk virus (reads on a Norovirus) peptides and method of detecting virus by using the antibody (See, abstract, para [0018], [0023], [0064], [0047]-[0057]). Kageyama et al 2004 discloses, as antigen peptides for a Norwalk virus (G1 antibody, antigen peptides composed of 4-6 amino acids selected from Met-Leu-Tyr-Thr-Pro-Leu (SEQ ID NO: 11) (See, para [0047]) and antigen peptides composed of 4-8 continuous amino acids selected from Ala-Met-Leu-Tyr-Thr-Pro-Leu-Arg (SEQ ID NO: 20) (See, para [0057]). Kageyama et al 2004 also discloses a method and a kit for detecting a Norwalk virus by using an antibody against the Norwalk virus (See, claims 7-15).
The amino acid sequence of the antigen peptide Met-Leu-Tyr-Thr-Pro-Leu (SEQ ID NO: 11) disclosed in Kageyama et al 2004 is identical to the sequence of 1-6th amino acids of the instant SEQ ID NO: 3 of the present invention, and is included in the amino acid sequences of the instant SEQ ID NOs: 1 and 2. Moreover, the sequence of 2-8th amino acids of the antigen peptide Ala-Met-Leu-Tyr-Thr-Pro-Leu-Arg (SEQ ID NO: 20) disclosed in Kageyama et al 2004 is identical to the amino acid sequence of the instant SEQ ID NO: 3, and is included in the amino acid sequences of the instant SEQ ID NO: 1 and 2.
Kageyama et al 2004 do not teach that (i) Norwalk virus is old name for Norovirus, and (ii) the claimed full length SEQ ID NOs: 1-3.
Robilotti et al 2015 teaches Human norovirus, previously known as Norwalk virus, was first identified in stool specimens collected during an outbreak of gastroenteritis in Norwalk, OH, and was the first viral agent shown to cause gastroenteritis (See, Introduction, entire article).
Robilotti et al 2015 do not teach the claimed full length amino acid sequence SEQ ID NOs: 1-3.
Kageyama et al 2002 teaches that instant SEQ ID NOs: 1 and 3 for the claimed instant peptides are comprised in VP1 protein sequence (See, Kageyama et al 2002, attached PDF printout of VP1 protein sequence for Accession YP_009700097).
1-MMMASKDAPTSPDGASGAGQLVPEANTAEQISMDPVAGASTAVATAGQVNMIDPWIFNNF
VQAPQGEFTISPNNTPGDILFDLQLGPHLNPFLAHLSQMYNGWVGNMRVRILLAGNAFTA
GKIIICCVPPGFDARILTIAQATLFPHLIADVRTLEPVELPLEDVRNVLYHNSSQPQPTM
RLVAMLYTPLRTGGGSGGTDAFVVAGRVLTCPAPDFSFLFLVPPSVEQKTRVFSVPNIPL
KDLSNSRVPVPIQGMFMSPDVNQSVQFQNGRCQIDGQLQGTTPVSLSQLCKIRGKTSSNA
RVLNLSEVDGTPFIPLESPAPVGFPDLGGCDWHVNFTFQAQNQDPSQSVTFATNDASFVP
YLGSISPHNGGDFHAGDIIGSLGWISAPSDNTQLNVWTIPKYGSSLPDVTHLAPAVFPPG
FGEVILYFYSTFPGSGQPSQLQVPCLLPQEFITHFCNEQAPIAGEAALLHYVDPDTGRNL
GEFKLYPDGFMTCVPNSVSSGPQTLPINGVFVFVSWVSRFYQLKPVGTASAARRLGLRRI-540
Instant SEQ ID NO: 1 (Qy)
Qy 1 MLYTPLRTGGGSGGTDPFVVAGR 23
|||||||||||||||| ||||||
Db 185 MLYTPLRTGGGSGGTDAFVVAGR 207
Instant SEQ ID NO: 3 (Qy)
Qy 1 MLYTPLR 7
|||||||
Db 185 MLYTPLR 191
Kageyama et al 2002 do not teach the claimed full length amino acid sequence SEQ ID NO: 2.
Richardson et al 2014 is in the art and is directed to a norovirus VLP to induce cross-reactive antibody response (production of anti-norovirus antibody) against norovirus genotypes and teaches SEQ ID NO: 8 that has 100 % identity with instant claim 1 SEQ ID NO: 2 (Qy) with a single conservative amino acid substitution.
Qy 1 RLVAMLYTPLRANGSGDDVFTVS 23
|||||||||||:|||||||||||
Db 177 RLVAMLYTPLRSNGSGDDVFTVS 199
The antibody or monoclonal antibody disclosed by Kageyama et al 2004 are an anti-norovirus antibody that engages in an antigen-antibody reaction with a peptide composed of a specific conserved amino acid sequence AMLYTPL that is comprised in the instant SEQ ID NOs: 1-3. As per the disclosure of Kageyama et al 2002 the instant SEQ ID NOs 1-3 are comprised in the VP1 sequence of a Norwalk virus (reads on a Norovirus). The instant SEQ ID NO: 2 is taught by Richardson et al 2014.
A single amino acid mismatch P17A (instant SEQ ID NO:1) with sequence taught by Kageyama et al 2002 (as recited above) is reasonably expected to not affect antigen-antibody interaction in absence of finding or disclosures in instant specification that are contrary. The intended application of the claimed antibody or monoclonal antibody is to develop immunoassay to detect a norovirus in a clinical sample. It is known in the art that there are diverse antigenic strains of a norovirus, and the developed immunoassay has to capture a norovirus antigen. The sequence MLYTPLR is common to all three claimed peptide sequences SEQ ID NOs: 1-3 and thus provides a reasonable basis for the claimed antibodies to cross react in an antigen-antibody interaction.
It would have been obvious to one of the ordinary skills before the effective filing date of the claimed invention to modify the prior art teachings of Kageyama et al 2004 on production and characterization (identification) or screening of antibody or monoclonal antibodies with additional teachings of Kageyama et al 2002 and Richardson et al 2014 on peptide sequences to identify and select antibody or monoclonal antibodies that bind to the instant claimed peptides of SEQ ID NOs: 1-3 to arrive at the inventions of claims 1-3 and 6 to obtain antibody or monoclonal antibody that bind to the claimed peptides (SEQ ID NOs: 1-3) of a norovirus to develop immunoassay for norovirus diagnostics and commercial success. There would have been a reasonable expectation of success to develop the claimed antibody or monoclonal antibody given the sequences of the peptides were known in the art, as recited supra, to develop antibody for immunodiagnostic assay for norovirus antigen or use of the protein or peptide to induce cross reactive antibody against a norovirus strains or genotype groups. The motivation would be to develop antibodies or monoclonal antibodies that are type-specific and cross-reactive antibodies as taught by Malm et al 2016 or Li et al 2010. Malm et al 2016 teaches type-specific and cross-reactive antibodies responses in norovirus VLP immunized mice are targeted both to conserved and variable domains of capsid VP1 protein (See, abstract, entire article, Table 2 epitope 2, row 2). Li et al 2010 teaches characterization of a cross-reactive monoclonal antibody against Norovirus genogroups I, II, III and V (See, abstract, entire article). The motivation would be that cross reactive antibodies are monoclonal antibodies are desirable to develop immunoassays to detect norovirus strains with antigenic diversity. 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 1-3 and 6. 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).
Double Patenting
18. 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.
19. Claims 1-3 and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of copending Application No. 18/562,099 in view of Kageyama et al 2004 (US20040073006A1, 04/15/2004) and further in view of Li et al 2010 (Virus Res. 2010 Aug;151(2):142-7) and Malm et al 2016 (Mol Immunol. 2016 Oct; 78:27-37).
The instant claims 1-3 and 6 are directed to antibody or monoclonal antibody that binds to norovirus peptide sequences disclosed in instant SEQ ID NOs: 1-3.
The reference co-pending claims 1-3 are directed to an immunoassay that utilizes 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. The reference claim 2 comprise a monoclonal antibody. The reference claim 3 comprises 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. As seen below in the Table indicates that instant SEQ ID NO: 1-3 teaches reference SEQ ID NOs: 1 and 2.
Instant Application
Peptide Sequence
Reference
Applcation
Peptide Sequence
18/562,078
SEQ ID NO: 1
MLYTPLRTGGGSGGTDPFVVAGR
18/562,099 SEQ ID NO: 1
MLYTPLRTGGGSGGTDPFVVAGR
18/562,078
SEQ ID NO: 2
RLVAMLYTPLRANGSGDDVFTVS
18/562,099 SEQ ID NO: 3
RLVAMLYTPLRANGSGDDVFTVS
18/562,078
SEQ ID NO: 3
MLYTPLR
It would have been obvious to one of the ordinary skills before the effective filing date of the claimed invention to develop variant reference claims based on the instant claims and arrive at the reference claims 1-3 in view of combined teachings of Kageyama et al 2004 on production of antibody or monoclonal antibodies to develop a norovirus immunoassay for commercial success. The motivation would be to develop immune assays using antibodies or monoclonal antibodies that are type-specific and cross-reactive antibodies as taught by Malm et al 2016 or Li et al 2010. Malm et al 2016 teaches type-specific and cross-reactive antibodies responses in norovirus VLP immunized mice are targeted both to conserved and variable domains of capsid VP1 protein (See, abstract, entire article, Table 2 epitope 2, row 2). Li et al 2010 teaches characterization of a cross-reactive monoclonal antibody against Norovirus genogroups I, II, III and V (See, abstract, entire article). The motivation would be that cross reactive antibodies are monoclonal antibodies are desirable to develop immunoassays to detect norovirus strains with antigenic diversity. 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).
This is a provisional nonstatutory double patenting rejection.
20. Related Prior Art References.
Rauch et al 2019. US20190125857A1 (2019-05-02). Artificial nucleic acid molecules encoding a norovirus antigen and uses thereof.
Xu et al 2021. Broad-range and effective detection of human noroviruses by colloidal gold immunochromatographic assay based on the shell domain of the major capsid protein. BMC Microbiol. 2021 Jan 11;21(1):22.
Parra et al 2013. Identification of a broadly cross-reactive epitope in the inner shell of the norovirus capsid. PloS one, 8(6), e67592.
Hansman, G. S., et al 2006. Genetic and antigenic diversity among noroviruses. The Journal of general virology, 87(Pt 4), 909–919.
Conclusion
21. No claim is allowed.
22. 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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