Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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Election/Restrictions
Applicant’s election without traverse of Species A (i.e., a single and specific glycan binding molecule as SEQ ID NO: 17); and Species B (i.e., a single and specific patient population to be treated/prevented as a SARS-CoV-2 infection) in the reply filed on July 9, 2025, is acknowledged.
Status of Claims
Claims 1-21 were originally filed on August 30, 2022.
The amendment received on August, 2022, canceled claims 13 and 18; and amended claims 1-12, 14-17, and 19-21.
Claims 1-12, 14-17, and 19-21 are currently pending and claims 1, 5-6, 8, 16, 19-21 are under consideration as claims 2-4, 7, 9-12, 14-15, and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 9, 2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/EP2021/055515 filed March 4, 2021, and claims priority under 119(a)-(d) to British Application Nos. 2003232.2 filed on March 5, 2020; 2004998.7 filed on April 4, 2020; and 2006160.2 file April 27, 2020.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for the British applications, which papers have been placed of record in the file. Please note that the British applications are in English and therefore no further action is necessary.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on August 30, 2022; June 9, 2023; July 9, 2025; and October 7, 2025, are being considered by the examiner.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Pursuant to MPEP 2111, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1).
Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention.
For claims 1, 16, and 21, please note that the instant specification does not define what is meant by “treatment” or “prevention”. However, the instant specification provides examples/embodiments of what is covered by “treatment”. More specifically, the instant specification teaches that “treatment” may embrace a reduction in one or more symptoms associated with a disease/condition caused or contributed to by a Coronavirus infection such as a continuous cough, a fever, change/loss in/of taste/smell (See instant, pg. 4, 1st paragraph). As such, the plain and ordinary meaning of each term applies. “Treat” is defined as to manage a disease by medicinal, surgical, or other measures; to care for a patient medically or surgically (See Medical Dictionary, “Treat”, Medical Dictionary, available online at https://medical-dictionary.thefreedictionary.com/treat, 3 pages (accessed on 2022)). “Prevent” is defined as to keep from happening or existing (See Merriam-Webster, “Prevent”, Merriam-Webster, available online at https://www.merriam-webster.com/dictionary/prevent, 9 pages (accessed 2025)). As such, “prevent” encompasses 100% prevention whereas “treat” does not. Also, please note that “Coronavirus” is defined as embracing any virus classed as belonging to the Family Coronaviridiae and embraces the SARS Coronavirus, the MERS Coronavirus, and the SARS-CoV-2 Coronavirus along with all SARS-CoV-2 variants (See instant, pg. 3, 3rd to 4th paragraphs). As such, the Coronavirus infection to be treated or prevented encompasses any Coronavirus.
Sequence Interpretation
For claim 20, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 17 with any N- and/or C-terminal additions. It is noted that Applicant’s elected SEQ ID NO: 17 is a fusion protein having a general structure of: CBMX1----CBMX2----TD where CBMX1 and CBMX2 are two identical monomers of instant SEQ ID NO: 6 (note: CBM40 derived from Streptococcus pneumoniae NanA sialidase) with three substitutions; namely, V239A, V246G, and A162P, TD is a trimerization domain derived from Pseudomonas aeruginosa sialidase (See GenBank Accession No. WP_411194140.1, 2 pages (2025) at residues 175/176 to 281) with two substitutions; namely, S342D and R403K, the first “----” is a peptide linker of GGGSG (i.e., instant SEQ ID NO: 21), and the second “----" is a peptide linker of GGSLG or GGSL. Moreover, regarding a glycan acid binding fragment of SEQ ID NO: 17, it is noted that there is no limit to the fragment thereby encompassing any fragment ranging from any dipeptide, a single CBM40 monomer, or a amino acid sequence with a deleted residue at the N- and/or C-terminus.
Specification
The disclosure is objected to because of the following informalities: on page 35, the description of Figure 1 describes the figure depicting colors, i.e., “rainbow colours” and “single colours”. However, Figure 1 is not in color, and color drawings have not been filed. It is respectfully requested that the description of Figure 1 accurately describe Figure 1. Alternatively, Applicants can file color photographs along with the necessary petition under 37 CFR 1.84(a)(2) and appropriate fee set forth in 37 CFR 1.17(h). Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Appropriate correction is required.
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.
Claims 1-2, 5-6, 8, 16, and 19-21 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 includes a “glycan binding molecule”. Independent claim 16 includes a “CBM40”. Independent claim 21 includes a “glycan acid binding molecule” that is Sp2CBM40TD. Dependent claim 5 includes where the glycan binding molecule comprises a “carbohydrate binding module (CBM)”. Dependent claim 6 includes where the CBM is selected from a “Family 40 CBM”. Dependent claim 19 includes where the “CBM comprises a modified CBM comprising a wild type CBM sequence which has been modified to include one or more mutations”. Dependent claim 20 includes where the modified CBM comprises SEQ ID NO: 17 or a “glycan acid binding fragment thereof.” With respect to a glycan binding molecule and CBM, it is noted that the instant specification does not define these terms. As such, the plain and ordinary meaning of the terms applies. Thus, the instant glycan binding molecule encompasses any molecule that binds to any glycan including proteins, peptides, oligonucleotides, and small molecules, etc. Similarly, the instant glycan acid binding molecule encompasses any molecule that binds to any glycan acid, i.e., sialic, glucuronic or galacturonic acids, including proteins, peptides, oligonucleotides, and small molecules, etc. The instant CBMs encompass any module that binds to any carbohydrate including proteins, peptides, oligonucleotides, and small molecules, etc. As such, the scope of claims 1 and 5 are extremely broad encompassing a vast array of distinct structural molecules or modules without a common core structure or sequence shared among the distinct species within the genera needed for the molecules or modules to bind any glycan or carbohydrate. With respect to the Family 40 CBMs, the instant specification teaches that they encompass molecules of approximately 200 residues and are often found at the N-terminus of GH33 sialidases, but can be found inserted in the beta-propeller of GH33 sialidases (See instant, pg. 11, 3rd paragraph). Although the scope of claims 6 and 16 limit the CBMs to peptide-based CBMs, the structure of the peptide-based CBMs is vast without a common core structure or sequence shared among the species within the Family 40 CBMs needed for the modules to bind to a carbohydrate. Plus, the Family 40 CBM of claim 6 is not limited to full length CBMs, but rather include fragments and modified CBM amino acid sequences as recited in claims 7 and 19-20. The specification defines “modified” as referring to molecules which contain one or more mutations relative to a reference sequence (See instant, pg. 21, 6th paragraph). A “reference sample” can be any wild type CBM sequence (See instant, pg. 21, 7th paragraph). Moreover, the specification teaches that a “mutation” can include any alteration to a wild-type CBM molecule (See instant, pg. 22, last paragraph). As such, a modified CBM40 encompasses where any wild type CBM40 derived from any organism has one or more mutations thereby encompassing any number of substitutions, deletions, insertions and/additions to the wild type CBM40 sequence. Similarly, CBM being a V. cholerae NanH sialidase fragment, a S. pneumoniae nanA sialidase CBM fragment, or a fragment of SEQ ID NO: 17 encompasses any fragment length ranging from a single deleted residue at either termini to any dipeptide. Thus, the Family 40 CBM, modified CBMs, and CBM fragments encompass a vast array of amino acid sequences without a common core structure or sequence shared among species within the claimed genera needed to bind to a carbohydrate, sialic acid, or glycan acid. Therefore, the scope of the claimed inventions encompass a vast array of molecules and modules without a common core structure or sequence in order for the molecule and/or module to function as claimed.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Cummings et al. teaches that antibodies, lectins, microbial adhesions, viral agglutinins, and other proteins with CBMs, collectively termed glycan-recognizing probes (GRPs), are widely used in glycan analysis because their specificities enable them to discriminate among a diverse variety of glycan structures (See Cummings et al., “Chapter 48: Glycan-Recognizing Probes as Tools,” Essentials of Glycobiol., Varki et al., eds., 4th Ed., Cold Spring Harbor Laboratory Press, 22 pages (2022) at pg. 1, 1st paragraph). Furthermore, Liu et al. teaches that CBMs are a class of multi-module enzyme proteins with a function to bind to the carbohydrate substrate (See Liu et al., Polymers 14:17 pages (2022) at pg. 1, 1st paragraph). There are over 300,208 CBMs reported in the Carbohydrate Active enZYmes Database by April 2022 (See Liu, pg. 1, 1st paragraph). CBMs are small in size, flexible, stable, strong in identification, with strong plasticity, and they can be fused with enzymes or organisms to improve their functions (See Liu, pg. 2, 2nd paragraph). They are widely distributed in nature and are present in enzymes secreted by bacteria, fungi and archaea (See Liu, pg. 2, 4th paragraph). There are many ways to classify CBMs (See Liu, pg. 2, last paragraph). Based on structural, functional similarities and the different ligand binding sites, CBMs can be divided into three types, namely, surface-binding CBMs (type-A), glycan-chain-binding CBMs (type-B), and small-sugar-binding CBMs (type -C) (See Liu, pg. 2, last paragraph). The type-B CBM structure often contains grooves or cracks of different depths as depicted in Figure 1b (See Liu, pg. 3, last paragraph). Most type-B CBMs are produced by enzymes secreted by bacteria and interact with the free single-chain polysaccharide (See Liu, pg. 3, last paragraph). The typical configurations of type-C CBMs mainly interact with the end of the polysaccharide chain (See Liu, pg. 4, 1st paragraph). Due to steric hinderance, only monosaccharides, disaccharides, trisaccharides, or the terminal sugar group of polysaccharides bind to type-C CBMs (See Liu, pg. 4, 1st paragraph). Lectin was the first known type-C CBM (See Liu, pg. 4, 1st paragraph). As such, the prior art recognizes the vast array of glycan binding molecules and, more specifically, CBMs with varying structures and functions, and fails to identify a core structure or sequence shared among species within the claimed genera necessary for a molecule or module to bind a glycan or carbohydrate including modified CBMs and CBM fragments. Thus, the claims are directed to molecules and modules with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genera.
Alternatively, the written description requirement may be met by provided a representative number of species of the genus. In this, the specification does not provide any examples glycan binding molecules other than CBMs, in particular CBM32, 40, 47, 67, or 70 (See instant, pg. 7, 3rd paragraph). The specification only exemplifies one CBM32 amino acid sequence as SEQ ID NO: 1, which is a fragment derived from the full length Clostridium perfringens protein represented by SEQ ID NO: 2 (See instant, pg. 9, 3rd paragraph; pg. 10, 2nd to last paragraph), and can bind, for example, galactose, N-acetylgalactosamine, N-acetylglucosamine, and/or lactose (See instant, pg. 9, last paragraph). Although the specification teaches that a CBM fragment of SEQ ID NO: 1 includes any 5 up to 138 contiguous amino acids from SEQ ID NO: 1 (See instant, pg. 9, 4th paragraph), there is no discussion of a core structure or sequence necessary for a CBM32 fragment of SEQ ID NO: 2 to bind to a carbohydrate. Plus, the specification discusses several microorganisms that contain CBMs such as Cellvibrio mixtus, Clostridium perfringens, and Streptococcus pneumoniae (See instant, pg. 9, 2nd paragraph).
Regarding CBM40, the specification exemplifies two CBM40 amino acid sequences as SEQ ID NO: 4, which is a fragment derived from the full length Vibrio cholerae NanH sialidase protein represented by SEQ ID NO: 3, and as SEQ ID NO: 6, which is a fragment derived from the full length Streptococcus pneumoniae NanA sialidase protein represented by SEQ ID NO: 5 (See instant, pg. 11, 5th to last paragraph; pg. 12, 1st to last paragraph). These CBMs are known to bind to sialic acid (See instant, pg. 11, 3rd paragraph). The specification also teaches that a molecule can comprise from about residue 1 to about residue 150 of SEQ ID NOs: 3-4 (See instant, pg. 13, 2nd paragraph) thereby encompassing a fragment containing a single residue. Additional discussion of CBM40 fragments of SEQ ID NOs: 3 or 5 include any 5 to about any 191 contiguous amino acids (See instant, pg. 13, 4th paragraph; pg. 14, 4th paragraph). Regarding CBM47, the specification exemplifies one amino acid sequence as SEQ ID NO: 7, which is a fragment derived from the full length Streptococcus pneumoniae protein represented by SEQ ID NO: 8, and can bind to L-fucose, fucosyllactose, H-trisaccharide and/or Lewis antigen (See instant, pg. 15, 2nd and 5th to last paragraph). Similar to CBM32 and 40 fragments, the specification teaches that a carbohydrate binding fragment of SEQ ID NO: 7 can comprise anywhere between about 5 to about 144 contiguous amino acids (See instant, pg. 15, 4th paragraph). Regarding CBM67, the specification exemplifies one CBM67 amino acid sequence as SEQ ID NO: 9, which is a fragment derived from the full length Streptomyces avermitilis protein represented by SEQ ID NO: 10 and can bind to L-rhamnose (See instant, pg. 17, 2nd and 5th to last paragraph; pg. 18, 1st to 2nd paragraph). Fragments of SEQ ID NO: 9 include anywhere between about 5 to about 164 contiguous amino acids (See instant, pg. 17, 4th paragraph). Regarding CBM70, the specification exemplifies one CBM70 amino acid sequence as SEQ ID NO: 11, which is a fragment derived from the full length Streptococcus pneumoniae protein represented by SEQ ID NO: 12 and can bind to hyaluronan (See instant, pg. 19, 1st and 3rd to last paragraph; pg. 20, 1st to 2nd paragraph). Fragments of SEQ ID NO: 11 include anywhere between about 5 to about 157 contiguous amino acids (See instant, pg. 19, 2nd paragraph). As such, the specification exemplifies six CBM amino acid sequences with no shared core structure or sequence, and only SEQ ID NOs: 3-6 exhibiting similar carbohydrate binding properties. Notably, there are no examples of any fragments of SEQ ID NOs: 1, 4, 6-7, 9 and 11, which are CBM fragments of a full length protein. Thus, the exemplary CBMs that bind to different carbohydrates do not constitute a representative number of species that an ordinary skilled artisan can extend to the scope of the claimed genera of glycan binding molecules, CBMs, and CBM fragments. Therefore, the specification is not sufficient for the skilled artisan to envisage which molecules or modules will preserve function.
Additionally, regarding modified CBMs, the instant specification teaches 7 general structures, HEX1 to HEX6 and HEX17, to be used to make sialic acid/glycan binding molecules (See instant, pg. 23, last paragraph to pg. 24, 1st paragraph). Each of the 7 HEX structures are a fusion of two CBMs and a modified/mutant trimerization domain (See instant, pg. 23, last paragraph to pg. 24, 1st paragraph). However, it is noted that all CBM components of all 7 HEX structures include two of the same mutations, i.e., V239A and V246G (See instant, pg. 24, 1st paragraph). These two mutations are the only modifications to both CBMs of HEX4 to HEX6 (See instant, pg. 24, 1st paragraph). HEX1 includes three additional mutations of L170T, I286A, and Y292E; HEX2 includes two additional mutations of I286A and Y292E; HEX3 includes one additional mutation of I286A; and HEX17 includes one additional mutation of A162P (See instant, pg. 24, 1st paragraph). As such, the modified CBM sequences are similar requiring the same two mutations with two HEX units containing 3 mutations, one HEX unit containing 4 mutations and one HEX unit containing 5 mutations. Although the 7 HEX structures do not specify an amino acid sequence and encompass any CBM (See instant, pg. 24, 2nd paragraph), the modified CBMs correspond to a specific CBM40 amino acid sequence, i.e., SEQ ID NO: 5. Since the differing CBM sequences do not share a core sequence, the identified mutations for the 7 HEX units cannot be extrapolated to extend to other unrelated CBM sequences. In fact, the identified mutations do not even correspond to the other CBM40 amino acid sequence, SEQ ID NO: 3. As such, the exemplary modified CBMs do not constitute a representative number of species that an ordinary skilled artisan can extend to the scope of the claimed genus. Therefore, the specification is not sufficient for the skilled artisan to envisage other substitutions/deletions/additions/insertions at the other residue sites which preserve function nor to envisage those substitutions other than those claimed with an expectation that function will be preserved.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 1-2, 5-6, 8, 16, and 19-21 do not meet the written description requirement.
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.
Claims 1-2, 5-6, 8, 16, and 19-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of a SARS-CoV-2 infection by administering a therapeutically effective amount of SEQ ID NO: 17, does not reasonably provide enablement for (1) the treatment of a SARS-CoV-2 infection by administering any glycan acid binding fragments of SEQ ID NO: 17, and (2) the prevention of a SARS-CoV-2 infection by administering any glycan binding molecule, CBM, or glycan acid binding fragment including SEQ ID NO: 17. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. NOTE: the rejection is limited to examination of elected SEQ ID NO: 17 and fragments thereof.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
The eight In re Wands factors are applied to Claims 1-2, 5-6, 8, 16, and 19-21 as follows:
The Breadth of the Claims and The Nature of the Invention
Although addressing that the subject is suffering from a SARS CoV-2 infection or at risk of suffering from a SARS CoV-2 infection in claims 1, 16, and 21 by administering SEQ ID NO: 17 or a glycan acid binding fragment thereof as a glycan binding molecule comprising a Family 40 CBM with 3 specific mutations, a CBM40, and as a glycan acid binding molecule with the structure of Sp2CBM40TD, respectively. Applicants do not provide any evidence in the specification that any glycan binding molecule, CBM or glycan acid binding molecule including SEQ ID NO: 17 can prevent a SARS CoV-2 infection. The Specification does not define what constitutes “prevention” of a SARS CoV-2 infection. As stated in the “Claim Interpretation” section supra, “prevent” is defined as to keep from happening or existing (See Merriam-Webster, “Prevent”, Merriam-Webster, available online at https://www.merriam-webster.com/dictionary/prevent, 9 pages (accessed 2025)). As such, “prevent” encompasses 100% prevention whereas “treat” does not.
Furthermore, Applicants do not provide any evidence in the specification that any fragment of SEQ ID NO: 17 can treat a SARS CoV-2 infection. As discussed in the “Sequence Interpretation” section supra, a glycan acid binding fragment of SEQ ID NO: 17 encompasses any fragment ranging from a fragment having a deleted residue at the N- or C-terminus to any dipeptide of SEQ ID NO: 17. As such, the scope of the glycan acid binding fragments of SEQ ID NO: 17 encompasses a vast array of peptide fragments. Accordingly, claims 1-2, 5-6, 8, 16, and 19-21 are unduly broad with respect to preventing a SARS CoV-2 infection, and with respect to treating a SARS CoV-2 infection by administering any glycan acid binding fragment of SEQ ID NO: 17.
The State of the Prior Art
It is noted that there is currently no prior art that teaches administering any glycan binding molecule, CBM, or glycan acid binding molecule in order to prevent a SARS CoV-2 infection in a subject. Similarly, there is currently no prior art that teaches administering any glycan acid binding fragment of SEQ ID NO: 17 in order to treat a SARS CoV-2 infection in a subject.
The Level of Skill in the Art
Practitioners in this art (medical clinicians, pharmacists, doctors and/or pharmaceutical chemists) would presumably be highly skilled in the art for treatment and/or prevention of a SARS CoV-2 infection in a subject.
The Level of Predictability in the Art
The instant claimed invention is highly unpredictable. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (i.e., administering any glycan binding molecule, a CBM, or a glycan acid binding molecule including SEQ ID NO: 17 to a subject at risk of suffering from a SARS CoV-2 infection; administering any glycan acid binding fragment of SEQ ID NO: 17 to a subject suffering from a SARS CoV-2 infection), then there is a lack of predictability in the art. Moreover, it is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
In the instant case, Applicants do not demonstrate that any glycan binding molecule, a CBM, or a glycan acid binding molecule including SEQ ID NO: 17 administered to a subject at risk of suffering from a SARS CoV-2 infection is effective to 100% prevent the SARS CoV-2 infection. Similarly, Applicants do not demonstrate that any glycan acid binding fragment of SEQ ID NO: 17 administered to a subject suffering from a SARS CoV-2 infection is effective to treat a SARS CoV-2 infection. Rather, Applicants only demonstrate that 3 specific modified trimeric, hexavalent CBMs (i.e., Vc2BM40TD, which is a trimer of two monomers of instant SEQ ID NO: 3 derived from V. cholerae and a trimerization domain (hereinafter CBM1); Sp2CBM40TD, which is a trimer of two monomers of modified instant SEQ ID NO: 6 with 3 mutations of V239A, V246G and A162P derived from S. pneumoniae and a trimerization domain of instant SEQ ID NO: 14 with 2 mutations of S342D and R403K (hereinafter CBM2); and Cp2CBM32TD, which is a trimer of two monomers of instant SEQ ID NO: 1 derived from C. perfringens and a trimerization domain (hereinafter CBM3)) reduced SARS CoV-2 plaques in vitro, whether administered prior to or after viral exposure at two specific concentrations of 1 mg/ml or 3 mg/ml (See instant, Example 1 at pg. 36-40; Figures 2-6). However, it is noted that the specific amino acid sequences of CBMs1 and 3 are not provided in the specification, in particular, if these two CBMs are modified similar to the CBM2 amino acid sequence and what the amino acid sequence of the trimerization domain is. As such, without clarification, the instant specification only demonstrates a single species, i.e., CBM2 (also referred to in the specification as HEX17 or Neumifil), as effectively treating a SARS CoV-2 infection by reducing viral plaque levels in Example 1. Furthermore, the specification describes an in vivo hamster study evaluating the effectiveness of CBM2 on SAR CoV-2 infection symptoms (See instant, Example 3, pg. 41-47; Tables 1-4; Figure 7). The specification concludes that the CBM2 treated hamsters exhibited a generally lower average number of symptoms relative to the control group including fewer instances of labored breathing (Lb) (See instant, pg. 47 Table 4). As such, Example 3 in the specification demonstrates that the CBM2 (i.e., instant SEQ ID NO: 17) is effective in treating a SARS CoV-2 infection. Example 4 demonstrates that CBM2 interacts with the SARS CoV-2 Spike S1 protein from three different strains, i.e., the Wuhan strain, a South African strain, and a UK-Kent strain (See instant, Example 4, pg. 48-49; Figure 8).
Applicants appear to rely on the assumption that by providing evidence that instant SEQ ID NO: 17 treats a SARS CoV-2 infection in vitro and in vivo would exhibit similar intended results for the 100% prevention of a SARS CoV-2 infection by any glycan binding molecule and/or for the treatment of a SARS CoV-2 infection by any glycan acid binding fragment of instant SEQ ID NO: 17. However, such an assumption cannot be made because there is no indication that any glycan binding molecule including instant SEQ ID NO: 17 would 100% prevent a SARS CoV-2 infection, and because there is no indication that any glycan acid binding fragment of SEQ ID NO: 17 would treat a SARS CoV-2 infection. Additionally, since the Specification fails to demonstrate any data or evidence that any glycan binding molecule 100% prevents a SARS CoV-2 infection or that any glycan acid binding fragment of instant SEQ ID NO: 17 treats a SARS CoV-2 infection, there would be no way of determining without undue experimentation whether a representative number of glycan binding molecules and/or glycan acid binding fragments of SEQ ID NO: 17 exhibit such desired results. Without more experimentation demonstrating the efficacy of a representative number of glycan binding molecules and/or glycan acid binding fragments of SEQ ID NO: 17 that an ordinary skilled artisan can extrapolate to extend to the claimed genera for the treatment and/or prevention of a SARS CoV-2 infection, the level of unpredictability remains high. Therefore, it is unpredictable that any glycan binding molecules will prevent a SARS CoV-2 infection in a subject, and that any glycan acid binding fragment of instant SEQ ID NO: 17 will treat a SARS CoV-2 infection in a subject.
The Amount of Direction Provided by the Inventor.
The Presence or Absence of Working Examples, and
The Quantity of Experimentation Necessary
The specification does not enable any person skilled in the art to which it pertains (i.e. administering any glycan binding molecule, a CBM, or a glycan acid binding molecule including SEQ ID NO: 17 to a subject at risk of suffering from a SARS CoV-2 infection; administering any glycan acid binding fragment of SEQ ID NO: 17 to a subject suffering from a SARS CoV-2 infection) to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual prevention of a SARS CoV-2 infection by administering to a subject any glycan binding molecule, a CBM, or a glycan acid binding molecule including SEQ ID NO: 17, and/or with regard to the actual treatment of a SARS CoV-2 infection by administering to a subject any glycan acid binding fragment of SEQ ID NO: 17. Applicants fail to provide the guidance and information required to ascertain where the claimed glycan binding molecule, a CBM, or a glycan acid binding molecule will be effective against preventing a SARS CoV-2 infection, and/or where the claimed glycan acid binding fragment of SEQ ID NO: 17 treats a SARS CoV-2 infection without resorting to undue experimentation. Applicant's limited disclosure is noted but is not sufficient to justify claiming 100% prevention of a SARS CoV-2 infection and/or all glycan acid binding fragments of SEQ ID NO: 17 for treating a SARS CoV-2 infection.
Absent a reasonable a priori expectation of success for using a representative number of glycan binding molecules, CBMs and/or glycan acid binding molecules of the claimed invention to prevent a SARS CoV-2 infection, one skilled in the art would have to extensively test viral titer levels in vitro and in vivo. Similarly, absent a reasonable a priori expectation of success for using a representative number of glycan acid binding fragments of SEQ ID NO: 17 to treat a SARS CoV-2 infection, one skilled in the art would have to extensively test viral titer levels in vitro and in vivo. Since each prospective embodiment, and indeed future embodiments as the art progresses, would have to be empirically tested, and those which initially failed tested further, an undue amount of experimentation would be required to practice the invention as it is claimed in its current scope, because the specification provides inadequate guidance to do otherwise.
The amount of direction or guidance presented in the specification is limited to specific species for the treatment of a SARS CoV-2 infection and do not provide any direction or guidance for the prevention of a SARS CoV-2 infection. The Specification discloses two working examples, in particular Examples 1 and 3, related to treating a SARS CoV-2 infection. Example 1 demonstrates that 3 specific modified trimeric, hexavalent CBMs (i.e., Vc2BM40TD, which is a trimer of two monomers of instant SEQ ID NO: 3 derived from V. cholerae and a trimerization domain (hereinafter CBM1); Sp2CBM40TD, which is a trimer of two monomers of modified instant SEQ ID NO: 6 with 3 mutations of V239A, V246G and A162P derived from S. pneumoniae and a trimerization domain of instant SEQ ID NO: 14 with 2 mutations of S342D and R403K (hereinafter CBM2); and Cp2CBM32TD, which is a trimer of two monomers of instant SEQ ID NO: 1 derived from C. perfringens and a trimerization domain (hereinafter CBM3)) reduced SARS CoV-2 plaques in vitro, whether administered prior to or after viral exposure at two specific concentrations of 1 mg/ml or 3 mg/ml (See instant, Example 1 at pg. 36-40; Figures 2-6). However, it is noted that the specific amino acid sequences of CBMs1 and 3 are not provided in the specification, in particular, if these two CBMs are modified similar to the CBM2 amino acid sequence and what the amino acid sequence of the trimerization domain is. As such, without clarification, the instant specification only demonstrates a single species, i.e., CBM2 (also referred to in the specification as HEX17 or Neumifil), as effectively treating a SARS CoV-2 infection by reducing viral plaque numbers in Example 1. Example 3 demonstrates that CBM2 when administered to hamsters resulted in the treated hamsters exhibiting a generally lower average number of symptoms relative to the control group including fewer instances of labored breathing (Lb) (See instant, Example 3, pg. 41-47; Tables 1-4; Figure 7). As such, Example 3 in the specification demonstrates that the CBM2 (i.e., instant SEQ ID NO: 17) is effective in treating a SARS CoV-2 infection. However, as noted in “Breadth of the Claims and Nature of the Invention" Section, prevention encompasses 100% prevention. As such, the in vitro and in vivo studies used in the specification do not support 100% prevention of a SARS CoV-2 infection. Furthermore, as noted in “Breadth of the Claims and Nature of the Invention" Section, the scope of the claimed glycan binding molecules, CBMs, glycan acid binding fragments of SEQ ID NO: 17, encompass a vast array of molecules and modules without a core structure or sequence shared among the species allowing an ordinary skilled artisan to extrapolate the efficacy of a representative number of species to extend to the whole genera. As such, the efficacy of a single CBM, i.e., CBM2, is insufficient to constitute a representative number of species that an ordinary skilled artisan can extrapolate the efficacy of to extend to other species within the claimed genera. It is further noted that Applicants provide no data, examples, figures, etc. demonstrating that any glycan binding molecule, CBM, or glycan acid binding molecule is capable of preventing a SARS CoV-2 infection, or demonstrating that any glycan acid binding fragment of SEQ ID NO: 17 is capable of treating a SARS CoV-2 infection. In the absence of such information, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent 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,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “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.” Id. at p. 1005.
After applying the Wands factors and analysis to Claims 1-2, 5-6, 8, 16, and 19-21, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in Claims 1-2, 5-6, 8, 16, and 19-21 would not be enabled by the written disclosure excluding that of treating a SARS CoV-2 infection in a subject by administering instant SEQ ID NO: 17 as a glycan binding molecule, a CBM, and/or a glycan acid binding molecule. Therefore, Claims 1-2, 5-6, 8, 16, and 19-21, are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to administer any glycan binding molecule, any CBM, and/or any glycan acid binding molecule to a subject in order to prevent a SARS CoV-2 infection, or to administer any glycan acid binding fragment of SEQ ID NO: 17 to a subject in order to treat a SARS CoV-2 infection.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 5-6, 8, 16, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Taylor et al. US 2017/0007692 A1 published on August 30, 2022 (cited in the IDS received on 8/30/22), in view of Matrosovich, et al., Top. Curr. Chem. 367:1-28 (2015), and Coronaviridae Study Group of the Intl. Committee on Taxonomy of Viruses, “The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2,” Nat. Microbiol. 5:536-544 (March 2, 2020) (hereinafter referred to as “CSG article”).
For claims 1, 5-6, 8, 16, and 21, Taylor et al. claims a method of modulating or priming an immune response in a subject by administering an immunomodulatory amount or quantity of a sialic acid binding molecule to a subject in need thereof (See Taylor, claim 1). The immune response is a protective immune response which protects against an infection caused or contributed to by a pathogen (See Taylor, claim 4) where the pathogen can be a viral pathogen (See Taylor, claim 5). The immune response is protective against a bacterial, fungal, and/or viral infection (See Taylor, claim 22). The subject administered the sialic acid molecule is one that has or is at risk of infection by a pathogen (See Taylor, claim 9). The subject can be symptomatic of an infection and the sialic acid binding molecule is administered to modulate the immune system to facilitate resolution and/or clearance of the infection (See Taylor, claim 14). thereby constituting where administration of the sialic acid binding molecule treats the infection that the subject is suffering from. Thus, the teachings of Taylor et al. satisfy the claim limitation of a method of treating an infection as recited in instant claims 1, 16, and 21.
Taylor et al. claims that the sialic acid binding molecule comprises a single sialic acid binding molecule or two or more sialic acid binding molecules (See Taylor, claim 17). Taylor et al. also claims where the sialic acid molecule comprises one or more CBMs (See Taylor, claim 18) where the CBM comprises the sialic acid binding domain from S. pneumoniae NanA sialidase (SpCBM) (See Taylor, claim 19). The sialic acid binding molecule can comprise one or more CBMs, a plurality or multiple CBMs, a multivalent CBM, or two or more SpCBMs (See Taylor, claim 21). Moreover, the sialic acid binding molecule can further comprise an oligomerization domain (TD) (See Taylor, claim 23) such as an oligomerization domain derived from P. aeruginosa (See Taylor, claim 24). A specific embodiment of a sialic acid binding molecule is Sp2CBMTD (See Taylor, claim 26). As depicted in Figure 1, Sp2CBMTD contains two identical CBM40s derived from S. pneumoniae NanA sialidase, i.e., two monomers of SEQ ID NO: 4, conjugated to a trimerization domain derived from P. aeruginosa sialidase, i.e., SEQ ID NO: 6, where each of the two CBMs and trimerization domain are separated by a 5-amino acid linker (See Taylor, [0080], [0195]; Figure 1). More specifically, Taylor et al. teaches that the two 5-amino acid linker sequences are GGGSG, which links the first SpCBM to the second SpCBM, and GQALG, which links the second SpCBM to the TD (See Taylor, Table 3). As such, Taylor’ sialic acid binding molecule constitutes the instant glycan binding molecule as recited in