DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group III, claims 26-29, in the reply filed on 2/20/26, and the Species Election: Species D (one or more bacterial cell wall epitopes and one or more mimotopes of bacterial cell wall epitopes) on 5/1/26, is acknowledged. The traversal is on the ground(s) that it would not place a serious burden to examine more than one group at a time. Applicants argue that any search for the antigens of claim 1 would likely reveal the same references as the elected antibodies and the methods in the other Groups. It is also argued that the species would all encompass the same search as well. This has been fully and carefully considered but is not found persuasive because not only would it place a serious burden on the examiner to search all the possible different antibodies encompassed in the Genus, the additional groups of biologically/structurally and chemically different products would also be undue. As stated in the Restriction Requirement:
Inventions I and II are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, the immunogenic antigen can be used in an in vitro assay to determine the specificity of an antibody to the antigen. Inventions I and III are directed to related products. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed the products have materially different designs (structures). Invention I is drawn to an immunogenic antigen, whereas Invention III is drawn to an antibody reactive to an immunogenic antigen. Antibodies are proteins comprising two heavy chains and two light chains, whereas antigens do not have these structural characteristics and contain epitopes. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Inventions I and IV are directed to an unrelated product and process. Product and process inventions are unrelated if it can be shown that the product cannot be used in, or made by, the process. See MPEP § 802.01 and § 806.06. In the instant case, the method of Invention IV requires antibodies whereas the product of Invention I is an immunogenic antigen. Inventions I and V are directed to related products. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed are products that have materially different designs (structures). Invention I is drawn to an immunogenic antigen, whereas Invention V is drawn to a hybridoma. An immunogenic antigen is any substance, typically a peptide or small molecule such as a toxin, that induces an immune response. A hybridoma is a hybrid cell comprising a variety of cellular components (e.g. membrane, organelles, DNA, RNA). Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Inventions III and II are directed to an unrelated product and process. Product and process inventions are unrelated if it can be shown that the product cannot be used in, or made by, the process. See MPEP § 802.01 and § 806.06. In the instant case, the method of Invention II requires an immunogenic antigen whereas the product of Invention III is an antibody. Inventions II and IV are directed to related processes. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed have materially different designs (active steps). Invention II is drawn to a method comprising administering an immunogenic antigen or composition, whereas invention IV is drawn to a method comprising administering antibodies. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Inventions V and II are directed to an unrelated product and process. Product and process inventions are unrelated if it can be shown that the product cannot be used in, or made by, the process. See MPEP § 802.01 and § 806.06. In the instant case, the method of Invention II requires an immunogenic antigen whereas the product of Invention V is a hybridoma. Inventions III and IV are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case, the antibodies of Invention III can be used in an in vitro assay to determine their binding specificity to an antigen. Inventions III and V are directed to related products. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed are products that have materially different designs (structures). Invention III is drawn to antibodies, whereas the product of Invention V is a hybridoma (culture of hybrid cells). Antibodies are proteins comprising two heavy chains and two light chains, whereas cells comprise cell membranes, organelles, DNA, RNA, and other cellular components. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Inventions V and IV are directed to an unrelated product and process. Product and process inventions are unrelated if it can be shown that the product cannot be used in, or made by, the process. See MPEP § 802.01 and § 806.06. In the instant case, the method of Invention IV requires antibodies whereas the product of Invention III is a hybridoma (hybrid cells).
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because of separate classification: Each invention is recognized in the art as a separate subject. Group I classification is A61K 2039/6037. Group II classification is A61K 2039/543. Group III classification is A61K 2039/6037. Group IV classification is. A61K 2039/543 Group V classification is A61K 39/00. Different field of search: It is necessary to search for one of the inventions in a manner that is not likely to result in finding art pertinent to the other inventions (e.g., searching different classes/subclasses or electronic resources, or employing different search queries, or a different field of search is shown even though the two are classified together). Examination burden: claims drawn to antigens (Invention I) and antibodies (Invention III) will require additional consideration under 35 U.S.C. 101 to determine whether they are product of nature judicial exceptions. Claims drawn to methods (Inventions II and IV) will require additional consideration under 35 U.S.C. 112(a) to determine whether the disclosure provides sufficient enablement for one of ordinary skill in the art to perform the methods and achieve the intended outcomes.
With respect to the Species Election requirement, the instant claims allow for so many different combinations and sizes of different ‘immunogenic antigens’ from completely different sources comprising completely different epitopes from completely different proteins. The vast number of different antigens these claims describe cannot be examined on one application. Applicants are entitled to the search of one invention. As stated above, the claims comprise an improper Markush grouping as different structures with different functions are grouped together, e.g., antibodies drawn to completely different epitopes from different sources/Genus/species, etc.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-25, 30 and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claim Objections
Claim 26 is objected to because of the following informalities: it depends from a non-elected claim, e.g., claim 1. The claim should be rewritten in independent form to include all of the limitations of the base claim. Appropriate correction is required.
Improper Markush Grouping
Claim 26 and dependent claims 27-29 are rejected on the basis that they contain 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 in the claims 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: these antigens and epitopes do not have a common structure or function. They are vastly different from one another. They are from different sources, bacterial vs viral and of many different Genus and species. Additionally, epitopes can be as small as 5 amino acids and the laundry list of potential epitopes from a variety of completely different sources makes these T cell stimulating epitopes and bacterial and viral epitopes
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 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 26-29 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.
Instant claim 26 recites:
Antibodies that are specifically reactive to the immunogenic composition of claim 1 [claim 1: an immunogenic composition comprised of: a contiguous peptide containing: two or more bacterial cell wall or viral epitopes; or one or more bacterial cell wall or viral epitopes and one or more mimotopes of the one or more bacterial cell wall or viral epitopes; and an adjuvant comprised of a nanomaterial].
Claim 26 is vague and indefinite because it recites antibodies to any peptide with any one or more bacterial epitopes and any one or more mimotopes of the one or more bacterial cell wall epitope. There is no structure recited in the claims or amino acid sequences and the source of these epitopes is very broad. A 5-amino acid sequence from any bacteria and any influenza is incredibly large and with zero actual structure, let alone a more defined source, the metes and bounds of the invention are not understood. The mere recitation of a name, i.e., antibodies to any bacterial cell wall epitope and any mimotope, 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 these epitopes and a more accurate description of the source, which would allow for one to identify the claimed immunogenic antigen without ambiguity. Additionally, it is unclear if these are antibodies to a fusion polypeptide of cell wall epitopes and mimotopes. The claim also recites an adjuvant comprised of a “nanomaterial.” The metes and bounds of this ‘nanomaterial’ are not readily understood. It is unclear what is encompassed by this term and the adjuvant is an important component of raising the claimed antibodies and the immune response could different based on what this adjuvant encompasses. Dependent claims 27-29 do not provide enough detail to define the claimed antigen either. 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.
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 26-29 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.
Instant claim 26 recites:
Antibodies that are specifically reactive to the immunogenic composition of claim 1 [claim 1: an immunogenic composition comprised of: a contiguous peptide containing: two or more bacterial cell wall or viral epitopes; or one or more bacterial cell wall or viral epitopes and one or more mimotopes of the one or more bacterial cell wall or viral epitopes; and an adjuvant comprised of a nanomaterial].
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and lightchain variable regions of a given antibody, each of which consists of three CDRswhich provide the majority of the contact residues for the binding of the antibodyto its target epitope. The amino acid sequences and conformations of each ofthe heavy and light chain CDRs are critical in maintaining the antigen bindingspecificity and affinity which is characteristic of the parent immunoglobulin. It isexpected that all of the heavy and light chain CDRs in their proper order and inthe context of framework sequences which maintain their required conformation,are required in order to produce a protein having antigen-binding function andthat proper association of heavy and light chain variable regions is required inorder to form functional antigen binding sites. Even minor changes in the aminoacid sequences of the heavy and light variable regions, particularly in the CDRs,may dramatically affect antigen-binding function as evidenced by Rudikoff et al(Proc Natl Acad Sci USA 1982 Vol 79 page 1979). Rudikoff et al. teach that thealteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum et al. J. Mol. Biol. (1996) 262,732-745, analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right col) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col.).
De Pascalis et al. The Journal of Immunology (2002) 169, 3076-3084 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, 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.).
Vajdos et al. (2002) 320, 415-428, additionally state that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen (page 416, left col.). Holm et al. (2007) 44, 1075-1084 describes the mapping of an anti-cytokeratin antibody where although residues in the CDR3 of the heavy chain were involved in antigen binding unexpectedly a residue in CDR2 of the light chain was also involved (abstract). Chen et al. J. Mol. Bio. (1999) 293, 865-881. describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirelycomposed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866).
Wu et al. J. Mol. Biol. (1999) 294, 151-162. state that it is difficult to predict whichframework residues serve a critical role in maintaining affinity and specificity duein part to the large conformational change in antibodies that accompany antigenbinding (page 152 left col.) but certain residues have been identified as importantfor maintaining conformation.
The references cited above demonstrate that an antibody must comprise all 6 CDRs in order to maintain the antigen binding specificity and affinity which is characteristic of the immunoglobulin. Single VH or VL polypeptides would not bind antigen.
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 any bacterial cell wall epitope and one or more mimotopes of said bacterial cell wall epitope, and identifies some broad categories that might work, however, these descriptions, without more precise 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").
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 26 fails to provide any sequences for the epitopes. It allows for any Genus and/or Genus/species of all known bacteria as well as mimotopes. The size of an epitope is generally thought to be equivalent to 4-15 amino acids or 3-4 sugar residues. A single bacterium, has many different proteins (and polysaccharides) on its surface that collectively form its various structures, and each different protein may have many different epitopes. For example, a bacterial cell wall alone may contain over 100 different epitopes. Hemagglutinin (HA) and neuraminidase (NA) viral surface proteins undergo small amino acid changes, or “antigenic drifts,” which necessitate an annual update to the seasonal vaccination. Accordingly, the instant specification does not provide adequate written description for the broadly claimed invention. A peptide needs to be presented by an MHC I molecule for it to be able to elicit effector T cell responses. Most peptides presented by MHC molecules will not elicit an immune response as they do not evoke TCR specific recognitions by the T cell. Predicting the epitopes is highly unpredictable. The energetic balance of the TCR-pMHC interaction is one of the main drivers in the initiation of an immune response and it is known in the prior art from structural and mutagenesis studies that this balance is very delicate. Additionally, TCR interaction is highly cross-reactive, meaning that a single TCR will potentially be able to bind to thousands of peptides. This poses a serious hurdle to develop computational tools to predict immunogenicity based on structural calculations. In recent years, it has been shown that, when using fine-grained molecular dynamics (MD) simulations, one can to some extent predict TCR-pMHC interactions. Unfortunately, this approach is neither very precise nor feasible. For such calculations, high quality structures of the interacting molecules are needed, and the current available number of solved structures for TCRs is very limited. See post filing date, Schaap-Johansen et al (Front. Immunol. Vol. 12, September 2021. Pages 1-11).
Accordingly, the instant specification does not provide adequate written description for the broadly claimed invention. 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. Applicants have not described the genus of claimed nucleotides such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed. The size of an epitope is generally thought to be equivalent to 5-15 amino acids or 3-4 sugar residues. a single bacterium, has many different proteins (and polysaccharides) on its surface that collectively form its various structures, and each different protein may have many different epitopes. Therefore, immune responses are directed against many different epitopes of many different antigens of the same microbe. (For example, a bacterial cell wall alone may contain over 100 different epitopes.) . Accordingly, the instant specification does not provide adequate written description for the broadly claimed 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 [product] itself 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.
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).
One skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. "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.
The scope of the claim includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between genus members is permitted. The specification does not describe the claimed antibodies by complete structure/sequence. 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.
''To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (”[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.''). Thus, an applicant complies with the written description requirement 'by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.”Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"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.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163 does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. Claim 26 contains an enormous number of possible variations are enormous to any class. Since the MPEP states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is ''not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.'1 MPEP § 2163. Though the claims may recite some functional characteristics, e.g., epitope, the claims lack written description because there is no disclosure of a correlation between function and structure beyond those disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety to reflect this variance.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does ''little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.'') Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120, 121, 365(c), or 386(c)as follows:
Instant Claim 1 from which elected claims 26-29 depend recites “an adjuvant comprised of a nanomaterial” which is not found in the disclosure of parent application US 17/506,237, now U.S. Patent No. 12,403,189.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No US 17/506,237, now U.S. Patent No. 12,403,189, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Instant Claim 1 from which claims 26-29 depend recites “an adjuvant comprised of a nanomaterial” which is not in the disclosure of parent application US 17/506,237, now U.S. Patent No. 12,403,189.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 26-29 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Fischer et al (US 2015/0064198).
Fischer’s invention is directed to compositions and methods for treating a disease or disorder and/or enhancing the immune system of a patient and, in particular, vaccines of non-naturally occurring substances and vaccination methods for treating and/or enhancing the immune system against infection by Mycobacterium tuberculosis. Fischer teaches that the immunity enhancing antigens (IEAs) of the invention are created from chemically killed organisms, such as ethanol killed, or degradation products of ethanol-killed organisms. IEAs of MTB include, but are not limited to epitopic regions of the surface of Mycobacterium tuberculosis (MTB), and various selected regions and sequences of the MTB components including, but not limited to MTB heat shock protein, peptidoglycan (cell wall), mycolic acid and lipoarabinomannan (LAM). Preferred amino acid and nucleic acid sequences of the invention contain or encode one or more epitopes of an IEA for MTB, and/or additional epitopes specific for other infections such as, for example, a viral infection (e.g. influenza). Preferred IEAs of the invention include altered portions of peptidoglycan, mycolic acid and LAM, which are useful as peptide vaccines and/or peptide adjuvants. Also preferred are nucleic acid aptamers and peptide aptamers and other molecules that mimic the structure and/or function of the antigens or antibodies of the invention, e.g., mimotopes. See paragraph [0033]. Claims 9 and 10 of Fischer teach the peptides, further comprising an adjuvant. The adjuvant may also comprise alum, amino acids, proteins, lipid/water emulsion. Paragraph [0023] teaches the invention is also directed to methods of identifying one or more antibodies that activate phagocytizing cells, i.e., opsonic antibodies, comprising: providing a microbe; generating antibodies that are specifically responsive to the microbe: incubating the generated antibodies with the phagocytizing cells; determining an activity of the phagocytizing cells after incubation with the antibodies; and selecting the one or more antibodies that increase the activity of the phagocytizing cells as compared to a control. Preferably the microbe is live or killed MTB and optionally, the microbe can be treated with one or more chemical and/or physical agents. Preferably the chemical agent is ethanol or gluteraldehyde. Also preferably, the antibodies generated from a mouse and preferably monoclonal antibodies. [0039] Another embodiment of the invention comprises one or more antibodies that binds to one or more specific targets or pathogens, preferably one or more MTB epitopes that are IEAs of the invention optionally including one or more previously known epitopes. These antibodies, which may be either monoclonal or polyclonal, have surprisingly demonstrated antigen binding in ELISA assays to non-natural target MTB antigens, such as ethanol altered MTB, and demonstrate enhanced immune response to MTB and promote or enhance phagocytic clearance of MTB. Antibodies of the current invention that stimulate phagocytic function promote phagocyte activity to identify MTB, engulf the organism and then destroy the MTB bacilli. Antibodies enhance treatment, for example, by promoting phagocytosis of bacteria, stimulating T cell recognition of the foreign antigen (e.g. memory T cells) followed by cell-killing of infected cells, and overall immune system clearance of the infection. Antibodies of the invention have been developed to a number of antigen targets, including but not limited to mycolic acid of the surface of MTB, heat-shock proteins and other MTB antigens (e.g., 16 KD MTB heat-shock protein of SEQ ID NO 1). Paragraph [0040] teaches another embodiment of the invention is directed to multiple antibodies of the invention (polyclonal, monoclonal or fractions such as Fab fragments, single chains, etc.) that are combined or combined with conventional antibodies (polyclonal, monoclonal or fractions such as Fab fragments, single chains, etc.) into an antibody cocktail for the treatment and/or prevention of an infection. Combinations can include two, three, four, five or many more different antibody in combination with each directed to a different antigen including IEAs of the invention. Paragraph [0041] teaches antibodies to one or more different IEAs of the invention may be monoclonal or polyclonal and may be derived from any mammal such as, for example, mouse, rabbit, pig, guinea pig, rat and preferably human. Polyclonal antibodies may be collected from the serum of infected or carrier mammals (e.g., typically human, although equine, bovine, porcine, ovine or caprine may also be utilized) and preserved for subsequent administration to patients with existing infections. Administration of antibodies for treatment against infection, whether polyclonal or monoclonal, may be through a variety of available mechanisms including, but not limited to inhalation, ingestion, and/or subcutaneous (SQ), intravenous (IV), intraperitoneal (ID), and/or intramuscular (IM) injection, and may be administered at regular or irregular intervals, or as a bolus dose. Paragraph [0042] Monoclonal antibodies to one or more IEAs of the invention may be of one or more of the classes IgA, IgD, IgE, IgG, or IgM, containing alpha, delta, epsilon, gamma or mu heavy chains and kappa or lambda light chains, or any combination heavy and light chains including effective fractions thereof, such as, for example, single-chain antibodies, isolated variable regions, isolated Fab or Fc fragments, isolated complement determining regions (CDRs), and isolated antibody monomers. Monoclonal antibodies to IEAs may be created or derived from human or non-human cells and, if non-human cells, they may be chimeric MABs or humanized. Paragraph [0036] recites vaccines of the invention may contain one or multiple sequences and/or portions that are derived from the same or from different source materials or organisms. Source materials include, for example, proteins, peptides, toxins, cell wall components, membrane components, polymers, carbohydrates, nucleic acids including DNA and RNA, lipids, fatty acids, and combinations thereof. Exemplary conjugate vaccines include, but are not limited to conjugates of a surface protein of MTB, peptidoglycan, mycolic acid, or LAM with a protein such as tetanus toxin or diphtheria toxin. Fischer teaches combinations of epitopes from both MTB and other pathogens include, for example, peptide conjugates of MTB and influenza or another viral epitope, peptide conjugates of MTB with Diphtheria toxin (e.g. CRM), Clostridium tetani toxin and peptides and proteins, or another bacterial epitope, or peptide conjugates of MTB with Plasmodium falciparum or another parasitic epitope. Preferably, the peptide sequences of the invention (e.g. see Table 3, which includes peptide composites of MTB, peptide composites of influenza, and combined MTB-influenza composite peptides) are synthetic peptide vaccines that generate and/or enhance an immune response to a pathogenic infection such as, for example, MTB, influenza virus, or the etiological agents of cholera, malaria, leprosy, AIDS, and/or another infectious disease, and prevent and/or treat the disease and infection. . Exemplary conjugate vaccines include, but are not limited to conjugates of a surface protein of MTB, peptidoglycan, mycolic acid, or LAM with a protein such as tetanus toxin or diphtheria toxin. See paragraph 36.
Prior art not presently relied upon:
Xavier et al (WO 2019/006022 A1; provided by Applicants in IDS 1/31/23).
Xavier et al teaches an immunogenic antigen comprised of: a contiguous peptide containing two or more bacterial cell wall epitopes (Claim 1 "A method of preparing one or more peptides for an immunological composition."; Claim 9 "wherein the surface protein is a cell wall protein."; Claim 36 “wherein the immunological composition is a protective vaccine or tolerizing vaccine composition comprising one or more of the antigenic epitopes.", para [0158] "Synthetic peptides provide a particularly useful means to prepare multiple immunogens efficiently and to rapidly translate identification of mutant epitopes to an effective vaccine or immunogenic composition"; para [0159] "the drug formulation is a multi-epitope vaccine or immunogenic composition of long peptides. Such “long” peptides undergo efficient internalization, processing and cross-presentation in professional antigen-presenting cells such as dendritic cells.....In a preferred embodiment 20 or more peptides are prepared for immunization. In one embodiment, the neoantigenic peptide ranges from about 5 to about 50 amino acids in length."); and aT cell stimulating epitope and/or adjuvant adjuvant (para [0160] "The vaccine or immunogenic composition can further comprise an adjuvant and/or a carrier"; para [0162] "An adjuvant may also alter an immune response, for example, by changing a primarily humoral or Th2 response into a primarily cellular, or Th1 response’).
US 2013/0195909:
discloses a composite antigen vaccine. Claims 1 and 5 define the composite antigen as comprising a peptide with a contiguous amino acid sequence derived from a plurality of antigenic epitopes of one or more pathogens which includes bacteria. Claim 5 further discloses how the composite antigen can comprise an amino acid sequence of at least one epitope that does not exist naturally i.e., a mimotope. Paragraph 0055 further discloses how the plurality of epitopes can be specific for any of the various antigenic regions of the bacteria tuberculosis. Paragraph 0055 further discloses how the composite antigen can comprise epitopes that generate a T cell response. US 2013/0195909 differs to the current invention in that it doesn't explicitly disclose the antigenic region (i.e., epitopes) to be the cell wall of the bacteria. However, the skilled person would readily consider the bacterial cell wall epitopes an obvious choice.
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/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 6/19/26
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