DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 130-158 and the Species: antibodies in the reply filed on 8/4/26 is acknowledged.
Claims 132 and 133 comprise the non-elected species: lectins.
Claims 159-161 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The instant claims were not restricted from the grandparent application’s claims, e.g., 16/591,329, now US Patent No. 11,001,626. They were also part of elected Group I in that application.
Claim Rejections - 35 USC § 112-2nd paragraph
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 130-158 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 130 is vague and indefinite because the wording is confusing. It is unclear how many antigens are on the device. The language:
“A device for detecting the presence or absence of one or more tapeworm coproantigens from a fecal sample from a canine or feline subject, the device comprising a solid support having immobilized thereon binding reagents for detecting two or more tapeworm coproantigens selected from the group consisting of Taenia pisiformis, Taenia taeniaeformis or a coproantigen from a third tapeworm Dipylidium caninum”
makes it unclear if the device comprises two or more of coproantigen from one of the species, e.g., two or more antigens from just T.pisiformis, for example, or if both species are included. Appropriate correction and/or clarification is required.
Further, the binding reagents are not clearly defined in claim 130 and all dependent claims thereof. Are these antibodies? If so, to which antigens? What are the structures for the binding reagents? The mere recitation of a name, i.e., binding antigen to X, to describe the invention is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. The claim should provide any structural properties, such as the amino acid sequence of the antibody or the antigen to which it binds, which would allow for one to identify the protein without ambiguity. The mere recitation of a name does not adequately define the claimed reagents on the device. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claims 132 and 133 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of lectins or antibodies as binding reagents is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Binding specificity: Each can bind to a particular molecular structure — lectins to carbohydrates (glycans) and antibodies to antigens.
Origin: Lectins are found in many organisms, especially plants, fungi, bacteria, and invertebrates and antibodies are produced by B cells in the immune system of animals, either naturally (polyclonal) or via laboratory production (monoclonal).
Biological role: Lectins often function in cell recognition, pathogen attachment, or plant defense, while antibodies are part of the adaptive immune response to neutralize or mark pathogens for destruction
Structure: Lectins vary widely in shape and number of carbohydrate-binding domains; antibodies have a conserved Y-shaped structure with variable regions for antigen recognition.
In summary: Lectins and antibodies are similar in that they are specific-binding proteins that can cause agglutination and are used in detection, but they differ in what they bind, where they come from, and their biological functions. Lectins are carbohydrate-specific tools, while antibodies are antigen-specific immune molecules
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim 137 is vague and confusing because it is unclear what is encompassed by ‘worm wash material’. What is ‘E/S material? This abbreviation is not understood. The claim also does not stem from a method of isolating antigens so the extracts and their method of obtaining them and “TCA soluble material’ is indefinite and lacking in antecedent basis. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claims 138-158 are vague and indefinite because the binding reagents are defined by functional activities alone. The structure of the reagent which produces the non-cross reactivity of the various coproantigens is unclear. The description is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. The claim should provide any structural properties, such as the amino acid sequence of the antibody or the antigen to which it binds, which would allow for one to identify the protein without ambiguity. The mere recitation of a name does not adequately define the claimed reagents on the device. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
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 130, 131, 132(antibodies) and 134-158 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 11,001,626. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods of diagnosing in the patent claims use a device with:
a solid support, wherein the solid support has immobilized thereon one or more antibodies selected from the group consisting of:
(a) a first antibody capable of specifically binding a coproantigen from a first tapeworm species Taenia pisiformis, but not a coproantigen from a second tapeworm species Taenia taeniaeformis or a coproantigen from a third tapeworm species Dipylidium caninum;
(b) a second antibody capable of specifically binding the coproantigen from the second tapeworm-species, but not the coproantigen from the first tapeworm or the coproantigen from the third tapeworm species, and
(c) a third antibody capable of specifically binding the coproantigen from the third tapeworm species, but not the coproantigen from the first tapeworm species or the coproantigen from the second tapeworm species.
The device in the patented method claims (not restricted in the parent application) recite a device that is a solid support and has antibodies from the same antigens. The dependent claims recite the same additional antigens/binding reagents. The scope of the claims are not patentably distinct.
Claim Rejections - 35 USC § 112-Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 130, 131, 132(antibodies) and 134-158 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, for instance:
A device for detecting the presence or absence of one or more tapeworm coproantigens from a fecal sample from a canine or feline subject, the device comprising a solid support having immobilized thereon binding reagents for detecting two or more tapeworm coproantigens selected from the group consisting of Taenia pisiformis, Taenia taeniaeformis and Dipylidium caninum.
134. (New) The device of claim 130, further comprising one or more types of Giardia coproantigen, roundworm coproantigen, whipworm coproantigen, and/or hookworm coproantigen, wherein the one or more types of roundworm coproantigen, whipworm coproantigen, and hookworm coproantigen are specifically bound to the binding reagents.
137. (New) The device of claim 130, wherein: (a) the first binding reagent was raised against a whole extract of Taenia pisiformis, E/S material of Taenia pisiformis, Worm Wash material of Taenia pisiformis, or TCA soluble material of Taenia pisiformis; (b) the second binding reagent was raised against a whole extract of Taenia taeniaeformis, E/S material of Taenia taeniaeformis, Worm Wash material of Taenia taeniaeformis, or TCA soluble material of Taenia taeniaeformis; or (c) the third binding reagent was raised against a whole extract of Dipylidium caninum, E/S material of the Dipylidium caninum, Worm Wash material of Dipylidium caninum, or TCA soluble material of Dipylidium caninum.
138. (New) The device of claim 130, wherein the first binding reagent does not specifically cross- react with one or more coproantigens selected from the group consisting of: tapeworm Taenia taeniaeformis coproantigen, tapeworm Dipylidium coproantigen, hookworm coproantigen, roundworm coproantigen, whipworm coproantigen, Giardia coproantigen and parvovirus coproantigen.
139. (New) The device of claim 138, wherein the hookworm is Ancylostoma, the roundworm is Toxocara, and the whipworm is Trichuris.
140. (New) The device of claim 138, wherein the tapeworm Dipylidium is Dipylidium caninum; the hookworm is Ancylostoma caninum or Ancylostoma tubaeforme; the roundworm is Toxocara canis or Toxocara cati; the whipworm is Trichuris vulpis or Trichuris felis; the Giardia is Giardia lamblia; and the parvovirus is feline parvovirus or canine parvovirus.
141. (New) The device of claim 130, wherein the second binding reagent does not specifically cross-react with one or more coproantigens selected from the group consisting of: tapeworm Taenia pisiformis coproantigen, tapeworm Dipylidium coproantigen, hookworm coproantigen, roundworm coproantigen, whipworm coproantigen, Giardia coproantigen and parvovirus coproantigen.
The instant specification does not provide adequate written description for the scope of these claims. An antibody can be functionally defined by the antigen it binds to, and in combination with a negative feature (i.e. no binding to a second antigen) as long as the antigen is concretely defined in the claims. Here, neither the target antigens of the claimed antibodies are adequately defined, nor is it apparent how the invention contributes to achieve antibodies with no cross-reactivity to other tapeworm as a generally applicable concept. Further, the binding reagents in the claims are NOT even limited to antibodies. Therefore, a skilled person would have to embark on a research program without any teaching in the application as how to achieve the desired specificity which amounts to an undue burden. By analogy, a method of screening compounds does not enable the skilled person to know all the various compounds that could be obtained from a screening assay ("reach through" claims). Unless the claims adequately define the target antigen, there is no reasonable way forward.
Specifically, these claims recite the use of sets of antibodies, wherein the antibodies comprising the sets lack cross-reactivity with one another. While the development of a new antibody against a known target is within the abilities of a skilled worker, the feature of such antibodies lacking cross-reactivity against similar species introduces to their development a considerable research burden. Consequently, claims directed to the use of sets of antibodies which do not cross-react with targets other than those exemplified in the description (e.g., T. pisiformis, T. taeniaeformis, and D. caninum) claim a scope greater than that to which the applicants are entitled, and are thus unsupported. The description does not correctly and fully describe the invention. The description does not set out clearly the method of making the claimed antibodies. It is necessary that the claims adequately define the target antigens, in full, clear, concise and exact terms as to enable a person skilled in the art to practice the invention.
The purpose of the "written description" requirement is broader than tomerely explain how to "make and use"; the applicant must convey with reasonableclarity to those skilled in the art that, as of the filing date sought, he or she was inpossession of the invention. The invention is, for purposes of the "writtendescription" 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 fromits enablement provision; and adequate written description requires more than amere statement that it is part of the invention and reference to a potential methodfor isolating it. The nucleic acid itself [product] is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Possession 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. 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. 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'" (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus.
It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow." The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fires v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lilly and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description (see Enzo paraphrased above).
The claimed genera of any antibodies binding some coproantigens but not other have widely variable structures and associated functions. Furthermore, "Possession may not be shown by merely describing how to obtain possession of members of the claimed ,genus or how to identify their common structural features" (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the .gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description.
Page 67 of the instant specification teaches 3 specific monoclonal antibodies produced by Applicants ADX131, ADX184 and ADX226, but there is no deposit or an amino acid sequence for these antibodies and this single genus is not enough to provide written description for the scope of the instant claims. The scope of the claim includes numerous structural variants (i.e. fragments), and the genus is highly variant because a significant number of structural differences between genus members is permitted. The specification does not describe any members of the claimed genus by complete structure. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
There are no drawings or structural formulas disclosed of any of thesevarious antibodies. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which the antibodies possess the same lack of cross-reactivity/antibody binding and adequately detect the tapeworm antigens. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of antibodies on the device with only monoclonal antibodies ADX131, ADX184 and ADX226, and there is no deposit or an amino acid sequence for these antibodies which would enable one of skill in the art to find or produce these same monoclonal antibodies.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim Rejections - 35 USC § 112-Enablement
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 130, 131, 132(antibodies) and 134-158 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. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The instant claims are drawn to, for instance:
A device for detecting the presence or absence of one or more tapeworm coproantigens from a fecal sample from a canine or feline subject, the device comprising a solid support having immobilized thereon binding reagents for detecting two or more tapeworm coproantigens selected from the group consisting of Taenia pisiformis, Taenia taeniaeformis or a coproantigen from a third tapeworm Dipylidium caninum.
Neither the binding agents or the target antigens of the antibodies are adequately defined, nor is it apparent how the invention contributes to achieve antibodies with no cross-reactivity to other tapeworm as a generally applicable concept in instant claims 138, 139, 141, 144, 147 and 149, for instance. Therefore, a skilled person would have to embark on a research program without any teaching in the application as how to achieve the desired specificity which amounts to an undue burden. By analogy, a method of screening compounds does not enable the skilled person to know all the various compounds that could be obtained from a screening assay ("reach through" claims). Unless the claims adequately define the target antigen, there is no reasonable way forward. Specifically, these claims recite the use of sets of antibodies, wherein the antibodies comprising the sets lack cross-reactivity with one another. While the development of a new antibody against a known target is within the abilities of a skilled worker, the feature of such antibodies lacking cross-reactivity against similar species introduces to their development a considerable research burden. Consequently, claims directed to the use of sets of antibodies which do not cross-react with targets other than those exemplified in the description (e.g., T. pisiformis, T. taeniaeformis, and D. caninum) claim a scope greater than that to which the applicants are entitled, and are thus unsupported. The description does not correctly and fully describe the invention. The description does not set out clearly the method of making the claimed antibodies. It is necessary that the claims adequately define the target antigens, in full, clear, concise and exact terms as to enable a person skilled in the art to practice the invention.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
Further, Ferrara et al (Mabs. Feb. 2015. 7(1): 32-41; cited on PTO-1449 10/9/24) show the diversity of antibody structures that can bind to the same antigen. Per page 36, initial antibody library has a diversity of over 3 x 10^11. Antibodies that have some reactivity to the antigen are on the order of 10^5 to 10^6. They then screened these further.“The diversity of these polyclonals was also assessed by deep sequencing. Table 3 shows the analysis of the polyclonals at the highest stringency parameters. The number of unique HCDR3s range from 74 to 460 for the 6 polyclonals we analyzed.”(pg 35). “The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36). Also, on the first page it mentions that the ERBB2 [aka HER2/Neu] protein has over 1,200 commercially available antibodies. It doesn’t specify whether these all have different CDRs or not.
Edwards et al (J. Mol. Biol. 2003. 334: 103-118; cited on PTO-1449 10/9/24) teaches that over one thousand different antibodies, all different amino acid sequences, can be found that bind to a single protein. See abstract. Moreover, a high level of sequence diversity was observed in the VH CDR3 domains of these antibodies, with 568 different amino acid sequences identified. Only about 40% of these antibodies inhibited binding to the specific protein, BLys. Lloyd et al (Protein Engineering, Design and Selection. 2009. 22(3): 159-168) teach that over 5000 target-specific antibodies were isolated to 28 antigens and only 3340 modulate the biological function of the target antigen. See abstract. These references show the unpredictability of identifying therapeutic antibodies and specific structures.
Pascalis et al. (The Journal of Immunology (2002) 169, 3076-3084; cited on PTO-1449 10/9/24) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (2003) BBRC 307, 198-205; cited on PTO-1449 10/9/24), which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.).
Additionally, The Office notes that the issue is make and use, not make and test to see if the skilled artisan could use. In short, the instant application encompasses a plethora of antibody variants possessing the ability to bind and not bind any coproantigens from three different tapeworm Genus/species, and identifies some broad categories that might work, however, these descriptions, without moreprecise guidelines, amount to little more than "a starting point, a direction for further research." Genentech, 108 F.3d at 1366. See also Calgene, 188 F.3d at 1374 ("the teachings set forth in the specification provide no more than a 'plan' or 'invitation' for those of skill in the art to experiment practicing [the claimed invention]; they do not provide sufficient guidance or specificity as to how to execute that plan"); National Recovery Technologies, 166 F.3d at 1198 (stating that patent-in-suit "recognizes a specific need.., and suggests a theoretical answer to that need. It provides a starting point from which one of skill in the art can perform further research in order to practice the claimed invention, but this is not adequate to constitute enablement").
Page 67 of the instant specification teaches 3 specific monoclonal antibodies produced by Applicants ADX131, ADX184 and ADX226, but there is no deposit or an amino acid sequence for these antibodies to adequately identify them or make them. Further, this single genus is not enough to provide written description for the scope of the instant claims.
The instant specification does not describe the claimed invention in terms that will "enable any person skilled in the art.., to make and use" the invention commensurate in scope with the claims. At most, the specification will enable a person of ordinary skill in the art to attempt to discover how to practice the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 130-132, 135-137 and 153-158 is/are rejected under 35 U.S.C. 103 as obvious over Callan et al (Parasitology. 1992. 104: 347-355; provided by Applicants) and Shin et al (Vet. Parasitl. 2002. 194: 351-356; cited on PTO-1449 10/9/24), Lloyd et al (Immunology. 1978. 34: 939-945; provided by Applicants) and Allen et al (Parasitology. 1992. 104(2): 347-356; provided by Applicants)
Callan teaches an ELISA (solid support) with antiserum against Taenia pisiformis antigen extract. They also provided an assay with human taeniasis based on antibodies against T.solium. See abstract.
Shin et al teaches an ELISA with antigens and binding agents against Dipylidium caninum. See abstract.
Lloyd teaches antibodies against Taenia taeniaeformis in mice. IgM, IgA and IgG immunoglobulins were isolated from mouse serum and colostral whey by chromatography. Anti-u, anti-« and anti-y chain antisera were prepared in rabbits using fractions rich in IgM, IgA and IgG, respectively, and emulsified in Freund’s Complete Adjuvant. Immunoabsorption to render the antisera specific was performed with various immunoglobulin fractions or whole neonatal mouse serum cross linked to CNBr-activated Sepharose 4B (Pharmacia, Sweden). The specificity of the rabbit anti-z, anti-« and anti-y chain sera was demonstrated by immuno- electrophoresis and by indirect haemagglutination inhibition. Each antiserum showed specificity for the homologous immunoglobulin class and was inhibitable only by its specific immunoglobulin.
Allen et al teach a dipstick dot ELISA for detection of Taenia-specific coproantigens was developed. The test was based on a sandwich ELISA using antibodies raised against adult Taenia solium. Antibodies were absorbed to nitrocellulose paper previously adhered to acetate plastic to form dipsticks. Once blocked with 5% skimmed milk and dried the antibody-coated dipsticks were stable for several weeks at room temperature. Both micro and dot ELISA formats were genus specific although the dot ELISA was less sensitive than the micro ELISA based on the same antiserum. During field studies, in which the majority of samples were tested in rural villages soon after collection, 3728 samples were tested. All samples were also examined by microscopy using formol ether concentration and individuals questioned to determine whether they were aware of being infected. After the initial diagnostic work individuals were treated with taeniacidal drugs for worm recovery. Use of the coproantigen test significantly increased the number of cases diagnosed. Of the 41 cases diagnosed by the three diagnostic techniques combined 31 were detected by the dipstick assay making it the most sensitive technique employed. The specificity of the dipstick assay was 99.9% with a positive predictive value of 88.6%. The combined diagnostic approach did not, however, diagnose all cases. The coproantigen test was fast and easy to use. Further improvements may make the dipstick test suitable for wide-scale use in field studies and diagnostic laboratories.
Generation of antigen-specific antibodies that are not cross-reactive are a standard design choice, as are features such as labelling the antibody or attaching it to a solid support. One of ordinary skill in the art, as shown in cited reference above, knows how to create species specific antibodies based on the prior art teachings and is aware of the clinical relevance of T. pisiformis, T. taeniaeformis and D. canium. These antibodies were previously shown in solid support assays. Using two or more antibodies from T.pisiformis and/or T.taeniaeformis, and a third with or without the Taenia antigens would have been obvious to one of ordinary skill in the art at the time the invention was made since the reference teaches these antibodies and solid supports and a design choice of more than one antigen would be expected to increase detection and save time.
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