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
Applicant's election with traverse of Group I, Escherichia and Salmonella and the combination of SEQ ID:3, 4, 7 and 8 in the reply filed on 1-20-2026 is acknowledged. The traversal is on the ground(s) that it would not be an undue burden to search all of the claims and given the Examiner has not cited any art which discloses the shared technical features of the claims of Group I and II, the claims necessarily possess unit. This is not found persuasive because (i) burden is not a criterion in determining whether a restriction is proper when said restriction is made under PCT Rules 13.1 and 13.2 and (ii) the basis of finding of lack of unity was that the groups/species lack the same or corresponding technical feature and hence art need not be cited. Even if one were to state arguendo that the unifying technical feature are the antibodies used in the claimed methods, said feature is not a special technical feature as it does not make a contribution to the art (as exemplified by the Written Opinion filed on 7-14-2023 and the art rejections set forth below).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-5, 7-11, 13-20, 22 and 24-30 are pending. Claims 3, 8 and 26-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-2, 4-5, 7, 9-11 13-20, 22 and 24-25 are currently under examination.
Information Disclosure Statement
The Information Disclosure Statements filed on 10-13-2023, 6-25-2024 and 2-24-2026 have been considered. Initialed copies are attached hereto.
It should be noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 1-2, 4-5, 7, 9-11 13-20, 22 and 24-25 are objected to for reciting claim language drawn to non-elected inventions.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4-5, 7, 9-11 13-20, 22 and 24-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims1-4, 6, 8-9, 13-19, 21, 23-24 of copending Application No. 18/272,483 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to detecting species of multiple genera of bacteria generally and the use of the EC50C1, EC149C3 and EC162A3, PA51B2 and CP141A190.1 antibodies (identified by SEQ ID NO:s) specifically.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112
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.
Written Description
Claims 1-2, 4-5, 7, 9-11 13-20, 22 and 24-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to the use antibodies to simultaneously determine the presence and/or amount of two or more genera of Enterobacteriaceae generally and Salmonella and Escherichia species specifically (elected invention). The claims optionally require:
the antibodies bind to the ribosome proteins L7/L12 of the two or more bacterial genera (claim 5);
the antibody does not cross-react with components of non- Enterobacteriaceae bacteria (claim 7);
the antibody does not cross-react with non-bacterial components generally (claim 9) or organic components derived from a virus, plant and/or animal (claim 10);
the antibody has a heavy chain variable region with at least 80% sequence identity to SEQ ID NO:3 and a light chain variable region with at least 80% sequence identity to SEQ ID NO:4 (claim 13);
said method utilizing a detection antibody specific for two or more species of bacteria and a detection antibody having a detection label and wherein one of the detection antibodies is “specific” for two or more bacterial species and at least one “generic” antibody which binds five or more Enterobacteriaceae genera (claims 14-20);
the “specific antibody” has a heavy chain variable region with at least 80% sequence identity to SEQ ID NO:3 and a light chain variable region with at least 80% sequence identity to SEQ ID NO:4 (claim 22); and
the “generic antibody” has a heavy chain variable region with at least 80% sequence identity to SEQ ID NO:7 and a light chain variable region with at least 80% sequence identity to SEQ ID NO:8 (claim 24).
Consequently, the instant claims encompass a myriad of antibodies that bind to a multiplicity of differing bacterial species. The specification discloses three “specific antibodies” (EC50C1, EC149C3 and EC162A3) and two “generic antibodies” (PA51B2 and CP141A190.1) which are able to bind to the ribosome protein L7/12 of multiple species. Of these antibodies only the EC2149C3 and PA51B2 antibodies read on the elected invention. These antibodies meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, to that degree. However, the aforementioned claims are directed to encompass a vast genus of antibodies with undefined sequences and immunological characteristics. None of these antibodies meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The claims are drawn to a vast genus of antibodies that bind to bacteria in two more Enterobacteriaceae genera. To fulfill the written description requirements set forth under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. To adequately describe the genus of antibodies that bind to bacteria in two more Enterobacteriaceae genera, Applicant must adequately describe which combination of variable regions and framework (Fd) regions that give rise to an antibody with the claimed immunological characteristics. The specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the antibody and its recited function (specific antibody binding), so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of antibodies. Other than with regard to the aforementioned antibodies, the specification fails to disclose what combination of variable regions and Fd regions are essential for antibody binding, or which amino acids might be added, replaced or deleted so that the resultant domain peptide retains the binding specificity of its parent, or by which other amino acids the essential amino acids might be replaced so that the resultant peptide retains the binding specificity of its parent. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of antibodies to which the claims refer; and accordingly, the specification fails to adequately describe at least a substantial number of members of the claimed genus of antibodies.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"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." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”
And:
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
As evidenced by the teachings of Skolnick et al., the art is unpredictable. Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily bind to a given antibody. Moreover, as evidenced by Greenspan et al. (Nature Biotechnology 7: 936-937, 1999), defining epitopes is not as easy as it seems. Greenspan et al. recommends defining an epitope by the structural characterization of the molecular interface between the antigen and the antibody is necessary to define an "epitope" (page 937, column 2). According to Greenspan et al., an epitope will include residues that make contacts with a ligand, here the antibody, but are energetically neutral, or even destabilizing to binding. Furthermore, an epitope will not include any residue not contacted by the antibody, even though substitution of such a residue might profoundly affect binding. Accordingly, it follows that the immunoepitopes that can elicit antibodies that bind to a given antigen can only be identified empirically. Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of immunoepitopes, the skilled artisan could not immediately recognize or distinguish members of the claimed genus of antibodies. It is well settled that the exchanging of CDRs among between antibodies is not predictable. While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains and surrounding framework regions of antibodies. For example, Giusti et al. (Proc. Natl. Acad. Sci. USA. 1987 May; 84 (9): 2926-2930) teaches the specificity and affinity of an antibody is exquisitely sensitive to amino acid substitutions within the primary structure of the antibody, since only a single amino acid substitution in the heavy chain of an antibody completely altered the binding specificity of an antibody that binds phosphocholine, such that the altered antibody fails to bind phosphocholine but instead binds DNA (see entire document [e.g., the abstract]). This unpredictability of single amino acid changes in an antibody is underscored by Winkler et al (J. Imm., 265:4505-4514, 2000) who teach that single amino acid changes in antibody side chains can result in unpredictable and substantial changes in antibody specificity; (see entire document [e.g., the abstract]). Chien et al. (Proc. Natl. Acad. Sci. USA. 1989 Jul; 86 (14): 5532-5536) teaches that significant structural and functional changes in an antigen-binding site can be caused by amino acid substitutions in the primary structure of an antibody, including substitutions at a site remote from the complementarity determining regions of the antigen-binding domain; (see entire document [e.g., the abstract]). Similarly, but more recently, Caldas et al. (Mol. Immunol. 2003 May; 39 (15): 941-952) teaches an unexpected effect of substituting a framework residue upon binding specificity during the humanization of an antibody that binds CD18 (see entire document [e.g., the abstract]). Casadevall et al. (PNAS, Vol 109 No. 31, pages 12272-12273) underscores the importance of the framework regions with regard to antibody affinity and binding specificity.
Sela-Culang et al. (Frontiers in Immunology, 2013 Vol. 4, article 302, pages 1-13) clearly set forth the role of CDRs, framework regions and constant regions in antibody specificity and affinity. Sela-Culang et al. disclose that the belief CDRs of an antibody are responsible for antigen recognition while the constant domains mediate effector activation is an oversimplification and that some residues within the CDRs never participate in antigen binding while some off-CDR residues are critical for antigen interaction. Sela-Culang et al. further disclose that only 20-33% of the residues within the CDRs actually participate in antigen binding (see page 4) and that it is well established that some of the framework (FR) residues play an important role in antigen binding (see page 7). This point is demonstrated by the fact that humanizing an antibody by grafting only the CDRs usually results in a significant drop or complete loss of antigen binding. Sela-Culang et al. also discloses that the framework region residues that affect binding can be divided into two categories: those that contact the antigen (which can be close in sequence to the CDRs or far from the CDRs in sequence but are in close proximity to it in 3-D structure) and those that are not in contact with the antigen but affect antigen binding indirectly (which can be in spatial proximity to the CDRs and those that are not). The framework regions residues that are more distant from the paratope (i.e. binding residues) not only play a role in maintaining the overall structure of the Fv domains but may affect antigen binding itself by directing the relative orientation of the VH with relation to the VL and thus the orientation of the CDRs relative to each other (see page 7). Specific knowledge of the FR residues involved in antigen binding is critical for antibody design in general and for the humanization of antibodies in particular. Finally, Sela-Culang et al. disclose that the constant regions of antibodies play a role in antigen binding due to an allosteric influence of the constant domains on the structure of the variable domains as evidenced by the differences in affinity and specificities of antibodies with the same variable region but different isotypes. (see page 8).
Recently, describing antibodies by their functions was addressed in the Centocor decision (CENTOCOR ORTHO BIOTECH, INC. v ABBOTT LABORATORIES (Fed Cir, 2010-1144, 2/23/2011)). In said case the court stated”
To satisfy the written description requirement, "the applicant must 'convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention,' and demonstrate that by disclosure in the specification of the patent." Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541 F.3d 1115, 1122 (Fed. Cir. 2008) (quoting Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991)). Assessing such "possession as shown in the disclosure" requires "an objective inquiry into the four corners of the specification." Ariad, 598 F.3d at 1351. Ultimately, "the specification must describe an invention understandable to [a person of ordinary skill in the art] and show that the inventor actually invented the invention claimed." Id. A "mere wish or plan" for obtaining the claimed invention is not adequate written description. Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566 (Fed. Cir. 1997).
The court further opined that Centocor's suggestion
that our decision in Noelle and the PTO written description guidelines support the view that fully disclosing the human TNF-α protein provides adequate written description for any antibody that binds to human TNF-α. That suggestion is based on an unduly broad characterization of the guidelines and our precedent.
The court concluded that
While our precedent suggests that written description for certain antibody claims can be satisfied by disclosing a well-characterized antigen, that reasoning applies to disclosure of newly characterized antigens where creation of the claimed antibodies is routine. Claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described.
Moreover, 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 Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, 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 should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Even more recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) recently decided (and was unanimously affirmed by the U.S. Supreme Court) Amgen v. Sanofi, Aventisub LLC, 987 F.3d 1080, 2021 U.S.P.Q.2d 169 (Fed. Cir. 2021), which concerned enablement for claims drawn to antibodies. While said case was dealt with enablement it should be noted that:
One of Amgen's expert witnesses admitted that translating an antibody's amino acid "sequence into a known three-dimensional structure is still not possible." J.A. 3910; see also Decision, 2019 U.S. Dist. LEXIS 146305 , at *9 . Another of Amgen's experts conceded that "substitutions in the amino acid sequence of an antibody can affect the antibody's function, and testing would be required to ensure that a substitution does not alter the binding and blocking functions." J.A. 3891; see also Decision, 2019 U.S. Dist. LEXIS 146305 , at *9 .
Said expert testimony illustrates the unpredictability of the antibody arts and clearly sets forth the expectations of the skilled artisan.
Therefore, only the EC2149C3 and PA51B2 antibodies but not the full breadth of the claims meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Scope of Enablement
Claims 1-2, 4-5, 7, 9-11 13-20, 22 and 24-25 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 detection methods utilizing the EC2149C3 and PA51B2 antibodies, does not reasonably provide enablement for methods utilizing any other antibodies. 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/use the invention commensurate in scope with these claims.
The specification is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, see In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) states, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” “The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling” (MPEP 2164.03). The MPEP further states that physiological activity can be considered inherently unpredictable. With these teachings in mind, an enabling disclosure, commensurate in scope with the breadth of the claimed invention, is required.
The instant claims are drawn to the use antibodies to simultaneously determine the presence and/or amount of two or more genera of Enterobacteriaceae generally and Salmonella and Escherichia species specifically (elected invention). The claims optionally require:
the antibodies bind to the ribosome proteins L7/L12 of the two or more bacterial genera (claim 5);
the antibody does not cross-react with components of non- Enterobacteriaceae bacteria (claim 7);
the antibody does not cross-react with non-bacterial components generally (claim 9) or organic components derived from a virus, plant and/or animal (claim 10);
the antibody has a heavy chain variable region with at least 80% sequence identity to SEQ ID NO:3 and a light chain variable region with at least 80% sequence identity to SEQ ID NO:4 (claim 13);
said method utilizing a detection antibody specific for two or more species of bacteria and a detection antibody having a detection label and wherein one of the detection antibodies is “specific” for two or more bacterial species and at least one “generic” antibody which binds five or more Enterobacteriaceae genera (claims 14-20);
the “specific antibody” has a heavy chain variable region with at least 80% sequence identity to SEQ ID NO:3 and a light chain variable region with at least 80% sequence identity to SEQ ID NO:4 (claim 22); and
the “generic antibody” has a heavy chain variable region with at least 80% sequence identity to SEQ ID NO:7 and a light chain variable region with at least 80% sequence identity to SEQ ID NO:8 (claim 24).
Consequently, the instant claims encompass a myriad of antibodies that bind to a multiplicity of differing bacterial species. The specification discloses three “specific antibodies” (EC50C1, EC149C3 and EC162A3) and two “generic antibodies” (PA51B2 and CP141A190.1) which are able to bind to the ribosome protein L7/12 of multiple species. Of these antibodies only the EC2149C3 and PA51B2 antibodies read on the elected invention. These antibodies (and its use in the claimed method is fully enabled. However, the aforementioned claims are directed to encompass any and all antibias that bind to bacterial species in two or more Enterobacteriaceae genera. The specification is not enabling for any of these antibodies as it is silent as to what sequences (e.g. immunoepitopes and framework regions) are required for a given antibody to bind to a multiplicity of divergent bacterial species.
The specification fails to disclose what combination of variable regions, Fd regions and constant regions are essential for antibody binding and the other aforementioned immunological characteristics, or which amino acids might be added, replaced or deleted so that the resultant domain peptide retains the immunological characteristics of its parent, or by which other amino acids the essential amino acids might be replaced so that the resultant antibody retains the immunological characteristics of its parent. As evidenced by the teachings of Skolnick et al., the art is unpredictable. Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily bind to a given antibody. Moreover, as evidenced by Greenspan et al. (Nature Biotechnology 7: 936-937, 1999), defining epitopes is not as easy as it seems. Greenspan et al. recommends defining an epitope by the structural characterization of the molecular interface between the antigen and the antibody is necessary to define an "epitope" (page 937, column 2). According to Greenspan et al., an epitope will include residues that make contacts with a ligand, here the antibody, but are energetically neutral, or even destabilizing to binding. Furthermore, an epitope will not include any residue not contacted by the antibody, even though substitution of such a residue might profoundly affect binding. Accordingly, it follows that the immunoepitopes that can elicit antibodies that bind to a given antigen can only be identified empirically. Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of immunoepitopes, the skilled artisan could not immediately recognize or distinguish members of the claimed genus of antibodies. It is well settled that the exchanging of CDRs among between antibodies is not predictable. While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains and surrounding framework regions of antibodies. For example, Giusti et al. (Proc. Natl. Acad. Sci. USA. 1987 May; 84 (9): 2926-2930) teaches the specificity and affinity of an antibody is exquisitely sensitive to amino acid substitutions within the primary structure of the antibody, since only a single amino acid substitution in the heavy chain of an antibody completely altered the binding specificity of an antibody that binds phosphocholine, such that the altered antibody fails to bind phosphocholine but instead binds DNA (see entire document [e.g., the abstract]). This unpredictability of single amino acid changes in an antibody is underscored by Winkler et al (J. Imm., 265:4505-4514, 2000) who teach that single amino acid changes in antibody side chains can result in unpredictable and substantial changes in antibody specificity; (see entire document [e.g., the abstract]). Chien et al. (Proc. Natl. Acad. Sci. USA. 1989 Jul; 86 (14): 5532-5536) teaches that significant structural and functional changes in an antigen-binding site can be caused by amino acid substitutions in the primary structure of an antibody, including substitutions at a site remote from the complementarity determining regions of the antigen-binding domain; (see entire document [e.g., the abstract]). Similarly, but more recently, Caldas et al. (Mol. Immunol. 2003 May; 39 (15): 941-952) teaches an unexpected effect of substituting a framework residue upon binding specificity during the humanization of an antibody that binds CD18 (see entire document [e.g., the abstract]). Casadevall et al. (PNAS, Vol 109 No. 31, pages 12272-12273) underscores the importance of the framework regions with regard to antibody affinity and binding specificity.
Additionally, Jones et al. (Letters to Nature, Vol. 321, pages 522-525) disclose that:
“The culture supernatants of several gpt+ clones were assayed by radioimmunoassay and found to contain NIP-cap-binding antibody. The antibody secreted by one such clone was purified from the culture supernatant by affinity chromatography on NIP-cap-Sepharose, and by SDS-polyacrylamide gel electrophoresis the protein was indistinguishable from the mouse chimeric MVNP+IgE”. (see page 523).
Clearly demonstrating that they were not able to “predict” the activity of a given antibody construct. Additionally, Queen et al. (PNAS, Vol. 86, pages 10029-10033) disclose that they had to construct models (via a computer program) to determine which portions of the murine FR regions must be maintained in order to preserve antibody binding as resides outside the CDRs can “either influence their conformation or interact directly with the antigen” (see page 10031). Again, Queen et al. had to screen a multitude of clones and empirically test them for binding activity (see page 10032). The art is replete with examples demonstrating that the unpredictability in determining antibody specificity and affinity. For example:
Winters and Harris (Immunology Today 14: 243-246, 1993) clearly set forth that when humanizing a murine antibody one needs to consider the interactions between the framework regions and the CDR loops and that all their “humanized antibodies” had to be empirically tested for specificity and affinity.
Moon et al. (Mol. Cells 39(3): 217-228, 2016) clearly state that “…residues that do not interact or contact antigen directly influence the interaction between the heavy and light chain, and thus increase binding affinity.”. This supports the Examiner’s position as if a change in the framework residues of an antibody can lead to an increase in binding affinity the converse is equally true (i.e. the change can lead to a decrease or ablation of binding and/or affinity). Moreover, it should be noted that Moon et al. was not able to predict which mutations would have a given effect. They had to utilize phage screening methods to determine which “mutants” maintained binding specificity.
Bendig et al. ("Humanization of Rodent Monoclonal Antibodies by CDR Grafting," Methods: A Companion to Methods in Enzymology, 8: 83-93, 1995) disclose a step-by-step process for making humanized antibodies using just the CDRs from a rodent antibody clearly states “In many cases, a rodent antibody that is humanized in a simple CDR graft will show little or no binding to antigen. It is important to study the amino acids of the human FRs to determine whether any of the amino acids are likely to adversely influence binding to the antigen, either directly through interactions with the antigen or indirectly by altering the positioning of the CDR loops” (see page 86). Again, as with all of the cited references, all of Bendig’s humanized antibodies had to be empirically tested for specificity and affinity.
Finally, Sela-Culang et al. (Frontiers in Immunology, 2013 Vol. 4, article 302, pages 1-13) clearly set forth the role of CDRs, framework regions and constant regions in antibody specificity and affinity. Sela-Culang et al. disclose that the belief CDRs of an antibody are solely responsible for antigen recognition while the constant domains mediate effector activation is an oversimplification as some residues within the CDRs never participate in antigen binding while some off-CDR residues are critical for antigen interaction. Sela-Culang et al. further disclose that only 20-33% of the residues within the CDRs actually participate in antigen binding (see page 4) and that it is well established that some of the framework (FR) residues play an important role in antigen binding (see page 7). This point is demonstrated by the fact that humanizing an antibody by grafting only the CDRs usually results in a significant drop or complete loss of antigen binding. Sela-Culang et al. also discloses that the framework region residues that affect binding can be divided into two categories: those that contact the antigen (which can be close in sequence to the CDRs or far from the CDRs in sequence but are in close proximity to it in 3-D structure) and those that are not in contact with the antigen but affect antigen binding indirectly (which can be in spatial proximity to the CDRs and those that are not). The framework regions residues that are more distant from the paratope (i.e. binding residues) not only play a role in maintaining the overall structure of the Fv domains but may affect antigen binding itself by directing the relative orientation of the VH with relation to the VL and thus the orientation of the CDRs relative to each other (see page 7). Specific knowledge of the FR residues involved in antigen binding is critical for antibody design in general and for the humanization of antibodies in particular. Finally, Sela-Culang et al. disclose that the constant regions of antibodies play a role in antigen binding due to an allosteric influence of the constant domains on the structure of the variable domains as evidenced by the differences in affinity and specificities of antibodies with the same variable region but different isotypes. (see page 8).
The unpredictability of the art regarding the was clearly summarized by Sir Gregory Paul Winter et al. as Amici Curiae, (submitted February 10, 2023, to the Supreme Court in Amgen Inc., et al., v. Sanofi, et al.) when he writes:
“Amgen’s expert further agreeing that even if antibody sequences were “similar”, that doesn’t tell you whether or not—whether an antibody binds to a particular region on a particular protein.” and further opines that “while it can be fairly said that an antibodies sequence determines its structure, which determines it function, an antibody scientist is unable to predict the function of an antibody from its sequence. Furthermore, an antibody scientist is unable to accurately predict how a change in the amino acid sequence of an antibody of known function may affect that function. The only way to know the function of a given antibody is to test it once it has been made.” (see page 15 of brief).
Recently the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, Aventisub LLC, 987 F.3d 1080, 2021 U.S.P.Q.2d 169 (Fed.
Cir. 2021), which concerned enablement for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. The court opined:
Wands did not proclaim that all broad claims to antibodies are necessarily enabled. Facts control and, in this court, so does the standard of review. In considering the Wands factors, the district court compared the present case to other cases in which we found lack of enablement due to the undue experimentation required to make and use the full scope of the claimed compounds that require a particular structure and functionality. For example, in Wyeth & Cordis Corp. v. Abbott Laboratories, we held that claims covering methods of preventing restenosis with compounds having certain functionality requirements were invalid for lack of enablement. See 720 F.3d 1380 , 1385-86 (Fed. Cir. 2013). Of particular significance, we held that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality.
The court further stated:
In cases involving claims that state certain structural requirements and also require performance of some function (e.g., efficacy for a certain purpose), we have explained that undue experimentation can include undue experimentation in identifying, from among the many concretely identified compounds that meet the structural requirements, the compounds that satisfy the functional requirement. Id. at 1100 n.2 (citations omitted).
That reasoning applies here. While functional claim limitations are not necessarily precluded in claims that meet the enablement requirement, such limitations pose high hurdles in fulfilling the enablement requirement for claims with broad functional language. See, e.g., Wyeth, 720 F.3d at 1384 (finding that practicing the full scope of the claims would require excessive experimentation); Enzo, 928 F.3d at 1345 (finding that the specification failed to teach whether the many embodiments would be both hybridizable and detectable upon hybridization); Idenix, 941 F.3d at 1155-56 (finding that the broad functional limitation of having efficacy against hepatitis C virus increased the number of nucleoside candidates that would need to be screened).
We also agree with the district court that this invention is in an unpredictable field of science with respect to satisfying the full scope of the functional limitations. One of Amgen's expert witnesses admitted that translating an antibody's amino acid "sequence into a known three-dimensional structure is still not possible." J.A. 3910; see also Decision, 2019 U.S. Dist. LEXIS 146305 , at *9 . Another of Amgen's experts conceded that "substitutions in the amino acid sequence of an antibody can affect the antibody's function, and testing would be required to ensure that a substitution does not alter the binding and blocking functions." J.A. 3891; see also Decision, 2019 U.S. Dist. LEXIS 146305 , at *9 . And while some need for testing by itself might not indicate a lack of enablement, we note here the conspicuous absence of nonconclusory evidence that the full scope of the broad claims can [*1088] predictably be generated by the described methods. Instead, we have evidence only that a small subset of examples of antibodies can predictably be generated.
Although the specification provides some guidance, including data regarding certain embodiments, we agree with the district court that "[a]fter considering the disclosed roadmap in light of the unpredictability of the art, any reasonable factfinder would conclude that the patent does not provide significant guidance or direction to a person of ordinary skill in the art for the full scope of the claims." Decision, 2019 U.S. Dist. LEXIS 146305 , at *11 . Here, even assuming that the patent's "roadmap" provided guidance for making antibodies with binding properties similar to those of the working examples, no reasonable factfinder could conclude that there was adequate guidance beyond the narrow scope of the working examples that the patent's "roadmap" produced.
The decision set forth:
One of Amgen's expert witnesses admitted that translating an antibody's amino acid "sequence into a known three-dimensional structure is still not possible." J.A. 3910; see also Decision, 2019 U.S. Dist. LEXIS 146305 , at *9 . Another of Amgen's experts conceded that "substitutions in the amino acid sequence of an antibody can affect the antibody's function, and testing would be required to ensure that a substitution does not alter the binding and blocking functions." J.A. 3891; see also Decision, 2019 U.S. Dist. LEXIS 146305 , at *9 .
The court concluded:
As the district court noted, the only ways for a person of ordinary skill to discover undisclosed claimed embodiments would be through either "trial and error, by making changes to the disclosed antibodies and then screening those antibodies for the desired binding and blocking properties," or else "by discovering the antibodies de novo" according to a randomization-and-screening "roadmap." Id. Either way, we agree with the district court that the required experimentation "would take a substantial [**8] amount of time and effort." 2019 U.S. Dist. LEXIS 146305, at *12. We do not hold that the effort required to exhaust a genus is dispositive. It is appropriate, however, to look at the amount of effort needed to obtain embodiments outside the scope of the disclosed examples and guidance. The functional limitations here are broad, the disclosed examples and guidance are narrow, and no reasonable jury could conclude under these facts that anything but "substantial time and effort" would be required to reach the full scope of claimed embodiments.
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court, held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. Similarly, the instant claims are drawn to a vast genus of antibodies that bind to a CD40 with no defined sequence and wherein only a portion of the specific structure is defined. Given, that there is no limitation regarding to the antibody’s sequence other than percent identity to a baseline sequence, no “specific structure” is defined by the claims as set forth by the Supreme Court. This is analogous to the fact pattern in the aforementioned Amgen case where Amgen argued that one could arrive at all the other antibodies by “conservative substitution” (in their citing of Morphosys AG v. Janssen Biotech). The Supreme Court specifically addressed this in the Amgen decision where they wrote:
“The second method is what Amgen calls “conservative substitution.” Id., at 14, 17. This technique requires scientists to: (1) start with an antibody known to perform the described functions; (2) replace select amino acids in the antibody with other amino acids known to have similar properties; and (3) test the resulting antibody to see if it also performs the described functions. See id., at 14–15.”
And further opined:
“Still, it says, its broad claims are enabled because scientists can make and use every undisclosed but functional antibody if they simply follow the company’s “roadmap” or its proposal for “conservative substitution.” We cannot agree. These two approaches amount to little more than two research assignments. The first merely describes step-by-step Amgen’s own trial-and-error method for finding functional antibodies—calling on scientists to create a wide range of candidate antibodies and then screen each to see which happen to bind to PCSK9 in the right place and block it from binding to LDL receptors. See Part I–B, supra; 987 F. 3d, at 1088; 2019 WL 4058927, *10–*13. The second isn’t much different. It requires scientists to make substitutions to the amino acid sequences of antibodies known to work and then test the resulting antibodies to see if they do too—an uncertain prospect given the state of the art. See Parts I–A, I–B, supra; 987 F. 3d, at 1088; 2019 WL 4058927, *10–*13.”
Given, the that the court found that making conservative substitutions within full disclosed antibody sequence (i.e. the 26 full length antibodies disclosed in Amgen) constituted undue experimentation, utilizing said method with only a partial antibody sequence would be even more “undue”.
Additionally, the Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id.
The Court also set forth that the specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art. Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 596, 2023 USPQ2d 602 (2023). For example, "it may suffice to give an example (or a few examples) if the specification also discloses some general quality . . . running through the class that gives it a peculiar fitness for the particular purpose" and "disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset." Id. at 611 (internal quotations omitted). However, while the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class which included "a ‘vast’ number of additional antibodies" that Amgen had not described by their amino acid sequences. Id. at 613. The Court found that Amgen sought to monopolize an entire class by their function, even though that class was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. Id. at 613. In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit explicitly applied the Wands factors to assess whether the specification of Amgen’s patent provided sufficient enablement, for purposes of 35 U.S.C. 112(a), to make and use the full scope of the claimed invention. The court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. See also the following cases across various technology areas: McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 2020 USPQ2d 10550 (Fed. Cir. 2020); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 107 USPQ2d 1273 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 2019 USPQ2d 415844 (Fed. Cir. 2019).
Therefore the Amgen decisions clearly set forth that claiming an antibody by partial structure and function is not enabling even when preparation of such an antibody is routine and conventional. Consequently, the specification, while being enabling detection methods utilizing the EC2149C3 and PA51B2 antibodies, does not reasonably provide enablement for methods utilizing any other antibodies.
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 2 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the use of any antibody or the contacting of the sample with any antibody so that an antigen-antibody reaction is produced.
Claims 1-2, 4-5, 7, 9-11 and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the inclusion of a detectable label or signal which is required to determine the presence and/or amount of a given bacteria.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-5, 7, 9-11 14-20 and 25 are rejected under 35 U.S.C. 102(a)(1) and/or 192(a)(2) as being anticipated by Matsuyama et al. (United States Application Publication US 20040014943 – IDS filed on 10-13-2023).
The claims are drawn to a method for detecting the presence and/or amount of bacteria in a sample selected from food or beverage samples, environmental samples, and biological samples, the method comprising the step of simultaneously detecting the presence and/or amount of at least bacteria of two or more different genera in the sample based on antigen-antibody reactions.
Matsuyama et al., disclose an anti-L7/L12 antibody for detecting bacteria. Matsuyama et al., describe an antibody for detection of microorganisms, a method of detection of microorganisms, and a reagent kit for detection of microorganisms, which is species specific for every species of microorganisms and with which all serotypes within the same species can be detected, are provided. Antibody to intracellular molecules with the same function in each type of microorganism, particular antibody to ribosomal protein, that is, ribosomal protein L7/Ll2, is made and antibody that reacts specifically with the microorganism in question is selected (see abstract). The L7/L12 antibody recognizes Hemophilus influenzae, Helicobacter pylori; S. pneumoniae; N. gonorrhoeae (see paragraphs 38-45 and 52]. Table 6 for discloses the simultaneous detection of Hemophilus influenzae, S. pneumoniae; and N. gonorrhoeae using the detection of microorganisms in the so-called sandwich assay by optical immunoassay and ELISA method, in combination with an anti-ribosomal protein L7/L12 antibody which is specific to each microorganism [para 222]. Matsuyama et al., further disclose the invention can be useful for detecting the species Chlamydia pneumoniae in test samples, such as from throat swabs, tissue samples, body fluids, experimental solutions and cultures (see paragraph 6).
It is well established that antibodies can be used in all known types of immunoassays, such as aggregation whereby said antibody is adsorbed on polystyrene latex, ELISA, which is a conventional technology performed in a microtiter plate, conventional immunochromatography, sandwich assay, whereby said antibody labeled with colored particles or particles that have coloring capability, or enzymes or phosphor, and magnetic particles coated with capture antibody are used (see paragraph 86). Moreover, antibody that is made based on the present invention can simultaneously function in any of these immunoassay methods as a so-called-capture antibody that captures said antigen protein in solid or liquid phase and a so-called enzyme-labeled antibody by modification using an enzyme, such as peroxidase and alkali phosphatase, etc., by conventional methods (see paragraph 87). The monoclonal antibody was used and evaluated as a capture antibody to be immobilized on a silicon wafer having a silicon nitride thin film layer (an insoluble membrane carrier) in the OIA method. Moreover, peroxidase-labeled AMGC-1 monoclonal antibody which can non-specifically react with ribosomal proteins L7/L12 protein of a variety of microorganisms described in Reference Example was used as the detect antibody [para 151]. Thus describing the detection steps of claim 14.
The antibody of the present invention specific to a variety of microorganisms that has been obtained by the methods can be used in a variety of immunoassay methods to obtain diagnostic reagent kits specific to a variety of microorganisms. For example, this antibody can be used in aggregation reactions where antibody is adsorbed on polystyrene latex particles, ELISA, which is a conventional technology performed in a microtiter plate, conventional immunochromatography methods, sandwich assay, whereby said antibody labeled with colored particles or particles that have coloring capability, or with enzyme or phosphor, and magnetic microparticles coated with capture antibody, etc., are used (see paragraph 68). An object of the present invention is also to provide a method for specifically and rapidly detecting a microorganism, a detection antibody used for the detection and a reagent kit for the detection. Furthermore, another object of the present invention is to provide a method for manufacturing the detection antibody used for the detection (see paragraph 224). Thus describing a capture and detection antibody just as instantly claimed. Finally, Matsuyama et al. disclose a method of detecting the microorganism comprising: a) contacting a test sample with a lysing solution, and extracting ribosomal protein from the microorganism; b) contacting the extracted test sample with a captured antibody, wherein said antibody is fixed on a solid surface, and forms an antigen-antibody complex from the ribosomal protein and the capture antibody, and c) detecting the antigen-antibody complex using a detection antibody (e.g. claim 14).
Therefore Matsuyama et al., anticipates all the limitations of the rejected claims.
Conclusion
No claim is allowed.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 May 11, 2026
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