DETAILED ACTION
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 .
Election Restrictions
Applicant’s election with traverse of Group I, claims 1-4, 9 and 10 drawn to an antibody or antigen fragment thereof, in the reply filed on 10/17/2025 is acknowledged.
Additionally, Applicant’s election of the following species:
the amino acid sequence of CDRH1: SEQ ID NO: 1
the amino acid sequence of CDRH2: SEQ ID NO: 2
the amino acid sequence of CDRH3: SEQ ID NO: 3
the amino acid sequence of CDRL1: SEQ ID NO: 4
the amino acid sequence of CDRL2: AAS
the amino acid sequence of CDRL3: SEO ID NO: 5
in the reply filed on 10/17/2025 is acknowledged.
The traversal is on the grounds that: “the pending claims are sufficiently related such that they do not represent an undue search burden on the Examiner. The disclosed SEQ ID NOs for CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3 in the present application possess high affinity and protective efficacy against various SARS-CoV-2 variants and recognizes spike protein of SARS-CoV-2 Wuhan strain (WHO1) and delta (B.1.617.2) variants of SARS-CoV-2 with EC50 values in the picomolar range in a cell-based binding assay. Further, as provided, the antibody or antigen-binding fragment thereof with the specified SEQ ID NOs for CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, CDRL3 in the present application possesses activity to neutralize SARS-CoV-2 Wuhan (WHO1), D614G, alpha (B1.1.7), and delta (B.1.617.2) pseudovirus with IC50 values in the picomolar range.”
This is not found persuasive because: as indicated in the Restriction Action more completely, the inventions in instant application are independent or distinct because they are related as product made and process of making, as product and process of use, and/or are directed to related but distinct processes. The rationale as to why restriction for examination purposes is proper, and the reasoning as to how all the inventions listed are independent or distinct and there would be a serious search examination burden was provided in the Restriction Action. Furthermore, there is additional consideration of enablement for the broad claim language of “A method for manufacturing” in claim 13 of Group II, “A method for treating or preventing infection” in claim 16 of Group III; and “A method for detecting” in claim 20 of Group IV; that would require further search/consideration.
Moreover, as indicated in the Restriction Action more completely, the species in instant Application are independent or distinct because: (SEQ ID NO:) sequences encoding different proteins are structurally distinct chemical compounds and are unrelated to one another. These sequences are thus deemed to constitute independent and distinct inventions within the meaning of 35 U.S.C. § 121. Absent evidence to the contrary, each such nucleotide sequence is presumed to represent an independent and distinct invention, subject to a restriction requirement pursuant to 35 U.S.C. § 121 and 37 CFR 1.141 et seq. (MPEP § 803.04).
Given that the reasoning for the Restriction Action was provided and that Applicant has not provided persuasive arguments as to how the inventions of Groups I-IV are not independent or distinct; the requirement is still deemed proper and is therefore made FINAL.
Claims 13, 16-18, 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/17/2025.
Preliminary Amendment and Status of the Claims
The preliminary amendment filed 10/17/2025, in which claims 1, 5-7 were amended and claims 4, 9, 11 were canceled is acknowledged and has been entered. Claim 19 was previously canceled.
Claims 1-3, 5-8, 10, 12, 14, 15, 21 are under examination on the merits.
Priority
Applicant’s claim for domestic benefit of prior-filed provisional application No. 63/266,008 filed on 12/27/2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
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. 63/266,008 filed on 12/27/2021, 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. Claim 2. Therefore, claim 2 does not receive domestic benefit to the provisional application No. 63/266,008 filed on 12/27/2021 because it does not disclose an omicron-CoV, as recited in claim 2. For purposes of applying prior art, the filing date for claim 2 is 12/27/2022.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 07/17/2023, 10/26/2023, 05/13/2024, 07/24/2024, 10/01/2024, 04/24/2025, 10/17/2025, 12/19/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, for example in page 25. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term “Tween-20” on page 26, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that “Tween-20” is merely an example and all improper uses of trademarks in the specification should be identified by Applicant and properly addressed.
The disclosure is objected to because of the following informalities: The Specification at ¶¶ [0077], refers to the antibody “m31A12” as comprising SEQ ID NOs: 1 to 5. The same paragraph, refers to the antibody “m37A12”. It is unclear if the antibody “m31A12” is the same as the antibody “m37A12”. Appropriate correction is required.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is defective because the size of the ASCII text file is in kilobytes instead of bytes.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claims 2, 3 are objected to because of the following informalities:
On claim 2, the recitation of “wherein the CoV is alpha-CoV, beta-CoV, gamma-CoV, delta-CoV2, or omicron-CoV.” should read “wherein the CoV is an alpha-CoV, a beta-CoV, a gamma-CoV, a delta-CoV2, or an omicron-CoV.” Appropriate correction is required.
On claim 3, the recitation of “wherein the CoV is SARS-CoV, MERS-CoV or SARS-CoV-2” should read “wherein the CoV is a SARS-CoV, a MERS-CoV or a SARS-CoV-2.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-8, 10, 12, 14, 15, 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “CDRH1 of an amino acid sequence of SEQ ID NO: 1… CDRH2 of an amino acid sequence of SEQ ID NO: 2… CDRH3 of an amino acid sequence of SEQ ID NO: 3… CDRL1 of an amino acid sequence of SEQ ID NO: 4… CDRL2 of an amino acid sequence of AAS… CDRL3 of an amino acid sequence of SEQ ID NO: 5…”. These recitations seem to be missing a verb. Further, it is not clear if Applicant intended to recite “comprising”, “consisting essentially of” or “consisting of” to define the scope of a claim in relation to the recited SEQ ID NOs. See MPEP 2111.03. The dependent claims do not add additional clarity and, therefore, are also indefinite. For the purposes of compact prosecution and applying prior art, claim 1 was interpreted herein as reciting the open-ended language of comprising the elected SEQ ID NOs.
Claim 5 recites “the amino acid sequence of CDRH1 is SEQ ID NO: 1… the amino acid sequence of CDRH2 is SEQ ID NO: 2… the amino acid sequence of CDRH3 is SEQ ID NO: 3… the amino acid sequence of CDRL1 is SEQ ID NO: 4… the amino acid sequence of CDRL2 is AAS, the amino acid sequence of CDRL3 is SEQ ID NO: 5…”. It is not clear if Applicant intended to recite “comprising”, “consisting essentially of” or “consisting of” to define the scope of a claim in relation to the recited SEQ ID NOs. See MPEP 2111.03. For the purposes of compact prosecution and applying prior art, claim 5 was interpreted herein as reciting the open-ended language of comprising the elected SEQ ID NOs.
Claims 1 and 5 recite an antibody comprising six CDR sequences which are fully defined (either by non-degenerate SEQ ID number or by spelling out the desired amino acid sequence in the case of CDRL2) as well as antibodies comprising CDR sequences which are “substantially similar sequences thereof”. It should be noted that SEQ ID NO:1 is an 8-mer, SEQ ID NO:2 is a an 8-mer, SEQ ID NO:3 is an 7-mer, SEQ ID NO:4 is a 10-mer, “AAS” is a tripeptide, and SEQ ID NO:5 is a 9-mer. The Specification at ¶ [0047] defines the term “substantially similar” is limited to sequences that are at least 90% identical to the reference sequence. Given that amino acid residues are integers (e.g. it is not possible to have say 2.7 or 4.2 amino acids in a peptide), to satisfy the minimum bound of 90%, the peptide sequence in question must minimally be 10 residues long with 9 of them being identical (i.e. 9/10 = 0.90). Of all of the recited CDR sequences, only SEQ ID NO:4 has 10 amino acid residues, while the other CRDs are smaller than 10 residues. Accordingly, for the CDRs smaller than 10 residues it appears to be impossible to make any mutation, conservative or otherwise, and yet satisfy the 90% or greater percent identity as mandated by the “substantially similar” language. As such, it appears that Applicant is attempting to claim antibodies with mutated sequences, yet it appears to be impossible to actually mutate the sequences in question, with the exception of SEQ ID NO:4, and meet the recited limitation of “substantially similar” as defined in the Specification. Given this apparent logical contradiction, it is not clear what the true metes and bounds of the claims are as either interpretation requires reading out part of the claim. Specifically, if mutations occur, the “substantially similar” must be ignored, and if mutations are not permitted, the recitation of “substantially similar” appears to have no purpose and fails to further limit the claim. The dependent claims do not add additional clarity and, therefore, are also indefinite. For purposes of compact prosecution and applying prior art, claims 1 and 5 were herein interpreted as referring to the SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, “AAS”, and SEQ ID NO:5 as defined by the disclosure, and SEQ ID NO:4 or a sequence at least 90% identical to SEQ ID NO:4.
Claim 2 recites “wherein the CoV is alpha-CoV, beta-CoV, gamma-CoV, delta-CoV2, or omicron-CoV.” This recitation is unclear for the following. First, it should be noted that the Coronaviridae family of viruses (CoV) comprises the subfamily Coronavirinae which comprises four genera, Alphacoronavirus (Alpha-CoV), Betacoronavirs (beta-CoV), Deltacoronavirus (delta-CoV), and Gammacoronavirus (gamma-CoV). There is no genus by the name of omicron-CoV in this subfamily. Further, the Specification (¶¶ [0077], [0119]) refers to variants of a SARS-CoV-2 which is a Betacoronavirus and not to the genera as recited in claim 2. The apparent incoherence between the claim language and the rest of the disclosure, renders claim 2 indefinite. The dependent claims do not add additional clarity and, therefore, are also indefinite. For purposes of compact prosecution and applying prior art, claims 2 was herein interpreted as referring to a CoV.
Claim 6 contains the trademark/trade name “nanobody”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a single-domain antibody fragment and, accordingly, the identification/description is indefinite.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this Office Action. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office Action.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5-8, 10, 12, 14, 15, 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 an antibody or antigen-binding fragment thereof that is specific for an epitope located in a spike protein of a SARS-CoV-2, it does not reasonably provide enablement for any antibody or antigen-binding fragment thereof that is specific for an epitope located in a spike protein that is not a SARS-CoV-2 virus or variant thereof. 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.
See claims 1-3, 5-8, 10, 12, 14, 15, 21 submitted on 10/17/2025.
In making a determination as to whether an application has met the requirements for enablement under 35 U.S.C. 112 P1, the courts have put forth a series of factors. See, In re Wands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. Id. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered. In the present case, the factors deemed relevant are those of: the breadth of the claims, the state of the art, the absence of working examples, and the quantity of experimentation necessary.
Nature of the invention and Breadth of the claims: Claims 1-3 of the present invention are drawn to an antibody or antigen-binding fragment thereof that is specific for an epitope located in a spike protein of a CoV (claims 1, 5-8, 10, 12, 14, 15, 21), wherein the CoV is alpha-CoV, beta-CoV, gamma-CoV, delta-CoV2, or omicron-CoV, (claim 2) and wherein the CoV is SARS-CoV, MERS-CoV or SARS-CoV-2 (claim 3). It is noted that the recitation of “wherein the CoV is alpha-CoV, beta-CoV, gamma-CoV, delta-CoV2, or omicron-CoV” is indefinite and is herein being interpreted as referring to a CoV.
State of the art and the unpredictability of the art: Regarding antibodies or antigen-binding fragment thereof that is specific for an epitope located in a spike protein of a SARS-CoV-2, the prior art teaches (See Chen et al., Rees-Spear et al. see citations below) challenges and great variability with respect to broadly neutralizing antibodies against coronaviruses.
With respect to antibodies or antigen-binding fragments thereof that are specific for an epitope located in a spike protein of a SARS-CoV-2, Chen et al. (Chen Z, et al. Genomic and evolutionary comparison between SARS-CoV-2 and other human coronaviruses. J Virol Methods. 2021;289:114032.) teach great genomic diversity among coronaviruses. For example, the complete genome sequence similarities between SARS-CoV and SARS-CoV-2 are only 79.4 ± 0.17 % (page 3). Further, Chen et al. further teach that both parametric and nonparametric algorithms support distinct separation of HCoV clusters, suggesting different evolutionary histories that the viruses may have encompassed within certain ecological niches or host animals before transmission to humans. Among seven identified human coronavirus clusters, SARS-CoV, SARS-CoV-2 and MERS-CoV are highly pathogenic and have been linked to the development of acute respiratory distress syndrome. The observed variation in codon usage between different HCoV clusters and their genes may suggest the presence of mutational bias and/or selective pressure that may impact translational efficiency (pages 7-8).
Further, Rees-Spear et al. (Rees-Spear, Chloe et al. “The effect of spike mutations on SARS-CoV-2 neutralization.” Cell reports vol. 34,12 (2021): 108890.) teach the effects of mutations on the spike protein on virus neutralization. Rees-Spear et al. further teach great genomic diversity among closely related human betacoronavirus accounting for notable differences in transmission dynamics and disease outcomes (pages 2-3). While SARS-CoV and SARS-CoV-2 both use the human ACE2 protein as a viral entry receptor and share approximately 75% similarity overall in spike at the amino acid level, there is considerable amino acid variation between the two receptor binding domains (RBDs), which explains why the majority of COVID-19 sera have weaker or no neutralizing activity against SARS-CoV (page 3). Thus, it is likely that a given antibody that binds a particular epitope on the spike protein of a specific coronavirus would not show cross-reactivity with other coronaviruses. In summary, Rees-Spear, et al. demonstrate a high level of unpredictability with respect to cross-reactivity comprising antibody epitopes of coronaviruses.
The amount of direction and the working examples provided: instant application teaches six examples (¶¶ [0110]-[0119]) which describe the isolation and characterization of the claimed antibodies against SARS-CoV-2 only (including variants thereof). The disclosure does not teach a single example of the binding of the claimed antibodies against any virus other than SARS-CoV-2. It is noted that the broadest claims in instant application read on any coronavirus (CoV). It is also noted that the data presented in the Drawings lack controls. The lack of controls renders the data meaningless and therefore do not provide support to the instant claims.
Quantity of experimentation necessary: As discussed above undue experimentation would be required to practice the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. In view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in specification, and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
In view of the foregoing, 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.
Claims 1-3, 5-8, 10, 12, 14, 15, 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 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.
See claims 1-3, 5-8, 10, 12, 14, 15, 21 submitted on 10/17/2025.
See also the 35 U.S.C. 112(b) rejections above.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
The instant claims require an antibody or antigen-binding fragment thereof that is specific for an epitope located in a spike protein of a CoV, wherein the antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs) of a heavy chain variable region and complementarity determining regions of a light chain variable region, wherein the complementarity determining regions of the heavy chain variable region comprise CDRH1, CDRH2, and CDRH3 regions, and the complementarity determining regions of the light chain variable region comprise CDRL1, CDRL2, and CDRL3 regions, and wherein:CDRH1 of an amino acid sequence of SEQ ID NO: 1 or a substantially similar sequence thereof, CDRH2 of an amino acid sequence of SEQ ID NO: 2 or a substantially similar sequence thereof, CDRH3 of an amino acid sequence of SEQ ID NO: 3 or a substantially similar sequence thereof, CDRL1 of an amino acid sequence of SEQ ID NO: 4 or a substantially similar sequence thereof, CDRL2 of an amino acid sequence of AAS or a substantially similar sequence thereof, and CDRL3 of an amino acid sequence of SEQ ID NO: 5 or a substantially similar sequence thereof.
The instant claims alternatively require an antibody or antigen-binding fragment thereof that is specific for an epitope located in a spike protein of a CoV, wherein the antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs) wherein sequence alterations such as substitutions, additions, insertions, or deletions of one or more amino acids can be made anywhere in the amino acid sequence of SEQ ID NO: 1-5, AAS including specific regions essential for antigen binding, provided that a CDR sequence is “a substantially similar sequence thereof” to SEQ ID NO: 1-5, and AAS. However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genus as to establish a structure-function relationship with respect to specificity for an epitope located in a spike protein of a CoV. It is noted that the term “substantially similar sequence thereof” is addressed under the 35 U.S.C. 112(b) rejections above.
However, while the claims are drawn to a genus of CDR sequences, the Specification has only adequately described and successfully reduced to practice the full-length of two sets of antibody CDRs, the first one comprising the CDR sequences in SEQ ID NO: 1-5, and AAS; and the second one comprising the CDR sequences in SEQ ID NO: 6-10, and AAT. This is not representative of the large genus of sequences claimed, since no variants, mutants, etc. of the claimed antibodies are demonstrated to have specificity for an epitope located in a spike protein of a CoV.
It has been well known in the art that minor structural differences even among structurally related compounds or compositions can result in substantially different biological or pharmacological activities. It is known in the art that the substitution of amino acids within the protein sequence may cause the loss of function of the protein. Thus, the large number of sequences encompassed by the current claims may or may not be effective in achieving the binding affinities of the claims. Specifically in relation to CDRs, it should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The structure of a typical antibody molecule. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27144/. See entire document). It is also known that single amino acid changes in a CDR can abrogate the antigen binding function of an antibody (Rudikoff et al. Single amino acid substitution altering antigen-binding specificity. Proc Natl Acad Sci U S A. 1982;79(6):1979-1983, see entire document, particularly the abstract and the middle of the left column of page 1982). Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
Moreover, Friedberg (“Automated protein function prediction--the genomic challenge”. Brief Bioinform. 2006;7(3):225-242.) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thorton (“Structural genomics takes off.” Trends Biochem Sci. 2001;26(2):88-89.) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thorton further describes examples of little correlation between specific binding function and overall protein structure (page 992, right column, at lines 2-10). Thus, when taken with the teachings of Friedberg and Thorton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least describe the structural features that are required for the claimed function, in this case specificity for an epitope located in a spike protein of a CoV. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to specificity for an epitope located in a spike protein of a CoV.
Thus, in view of the reasons set forth above, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Conclusion
No claims are allowed.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672