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 .
Preliminary Amendment
The preliminary amendment dated 11/19/2025 has been entered. Claims 76-93 are pending.
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. The earliest possible effective filing date for the instant claims is May 26, 2020 based on the filing date of the application EP20305550.4 The K417T, E484K, N501Y and C538S mutations (claim 90) are first described in EP21305092.5 with a priority date of January 26, 2021.
Election/Restriction
Applicant’s election with traverse of Group II in the reply filed on 11/19/2025 is acknowledged.
Claims 77, 79-84, 87 and 92-93 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. Claims 76, 85 and 91 being linking claims.
Claims 76, 78, 85, 88-91 are under examination.
Applicant’s species election in the reply filed on 11/19/2025 is acknowledged. Applicant elected conjugate CD40.N2.RBDv. The requirement for electing a species of linker is withdrawn.
The traversal filed by the Applicant is on the grounds that the present claims are unified for at least the following reasons:
(a) Claims 76, 85, and 91 link inventions I, II, and III (See Restriction requirement). Applicant submits that these claims link inventions IV and V as well, because claim 92 (Group IV) and claim 93 (Group V) depend on claim 76.
(b) Examining Groups I through V at once promotes efficiency for both the U.S. Patent and Trademark Office and Applicants while imposing no undue or serious burden to the Examiner. See M.P.E.P. § 803.
(c) The description of Group Il is inconsistent with the Examiner’s request for a species election. That is either ‘Gen2a’ or ‘Gen2b’ or ‘Gen2c’ or ‘CD40.CoV2v’ or ‘CD40.N2.RBDv’ or ‘CD40.N2.RBDv’-2 or ‘CD40.RBDv.S4.N2’ or ‘CD40.N2S1.RBDvS4. are not . Group II is supposed to cover all of “Gen2a’” or “Gen2b” or “Gen2c’” or “CD40.CoV2v’ or “CD40.N2.RBDv’ or “CD40.N2.RBDv’-2 or “CD40.RBDv.S4.N2” and “CD40.N2S1.RBDvS4’ conjugates. The definition of Group II should a minima be amended to cover the elected species of conjugate CD40. N2.RBDv.
Applicant’s arguments have been fully considered but are not found persuasive.
(a) The restriction requirement is stated that, as provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a
use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said
process; or
(5) A product, a process specially adapted for the manufacture of the said product, and
an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c), as is the case
for Groups I, II, III and IV that are drawn to different products, regardless of claim dependency. Groups V is drawn to a method, regardless of claim dependency. Applicant arguments do not contest the teaching of the reference(s) cited to establish a lack of unity for Group V.
(b) Search burden arguments do not apply when restriction is required under 35 USC 121 and 372, as in the instantly filed application. When the Office considers international applications as an International Searching Authority, as an International Preliminary Examining Authority, and during the national stage as a Designated or Elected Office under 35 U.S.C. 371, only PCT Rule 13.1 and 13.2 will be followed when considering unity of invention of claims of different categories without regard to the practice in national applications filed under 35 U.S.C. 111. Applicant arguments do not contest the teaching of the reference(s) cited to establish a lack of unity.
(c) A restriction requirement is not a full merits examination. The examiner can list all species in a claim with the expectation that the applicant would know which species would make sense based on the elected invention. The applicant elected as a species CD40.N2.RBDv. Applicant did not elect CD40.N2.RBDv-2 also listed in the species election requirement. However, and as requested by the applicant (Response to restriction requirement and species requirement page 4), examiner has amended Group II to include the elected species and also to more accurately define the actual product (a conjugate peptide) of the group as follows:
Group II, claims 78 and 88-90 drawn to a conjugate wherein a heterologous polypeptide is fused to a polypeptide (Npep2) from the SARS-CoV-2 N protein and a Receptor Binding domain (RBD), and a CD40 antibody defined either by the heavy chain fused only to the RBD polypeptide and by the light chain fused only to Npep2 polypeptide or by the heavy chain fused only to Npep2 polypeptide and by the light chain fused only to RBD polypeptide. The elected species being CD40.N2.RBDv
The requirement is deemed proper and is therefore made FINAL.
Specification Objections
The abstract of the disclosure is objected to because of implied phraseology (e.g. “The present disclosure provides…” and “The present disclosure further provides…”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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.
https://www.ebi.ac.uk para [0014]; www.bioinf.org.uk [0046]; https://services.healthtech.dtu.dk/service.php?NetMHC-4.0 and https://services.healthtech.dtu.dk/service.php?NetMHCII-2.3 [0234]; https://services.healthtech.dtu.dk/service.php?BepiPred-2.0 [0235]; https://services.healthtech.dtu.dk/service.php?BepiPred-2.0; https://doi.org/10.1101/2020.12.24.20248822; https://doi.org/10.1101/2020.12.21.20248640; https://doi.org/10.1101/2020.12.31.425021 [0016]
Claim Objections
Claims 76 and 88 are objected to because of the following informalities: Abbreviations, acronyms and names should be enclosed within parentheses only. The quotation marks are unnecessary. For example, (“Npep2”) should be written as (Npep2). (“CD40.N2.RBDv”) should be written (CD40.N2.RBDv), etc.. Appropriate correction is required for all claims when the quotation marks and parenthesis are present together.
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 76, 78, 85, 88 and 90 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 76, 85 and 88 recite the limitation Npep2. it is unclear what Npep2 is, Npep2 as defined in the claim of what is “Npep2” is different from what is in the specification. In the specification the definition is as follows: polypeptide that derives from the protein N and that consists of at least 50 consecutive amino acids of the amino acid sequence having at least 90% of identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2 [0083]. In claim 76 it is defined as polypeptide that derives from protein N of SARS-CoV-2 and that comprises at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2. The definition in the claim needs to be the same as it is in the specification. For the purpose of compact prosecution, the claim has been interpreted as “…consists of at least 50…”.
Appropriate correction is required.
Claim 76 recites the limitation “….. 50 consecutive amino acids of the amino acid sequence having at least ….”. There is insufficient antecedent basis for “the amino acid sequence ” limitation since there is no previously recited amino acid sequence.
Claims 76 and 85 recite the limitation “…a heterologous polypeptide….” It is unclear what the term heterologous refers to (heterologous to what? Npep2?, the nucleocapsid? any protein of SARS-CoV-2? anything else?). There are multiple interpretation of “heterologous” and therefore the term renders the metes and bounds of the claim indefinite.
Claim 78 recites the limitation: "The conjugate of Claim 76, comprising a receptor binding domain (RBD) polypeptide”. It is unclear if the RBD is in addition to the heterologous polypeptide or if it is the heterologous polypeptide. For the purpose of compact prosecution this claim has been interpreted as "The conjugate of Claim 76, wherein the heterologous polypeptide comprises a receptor binding domain (RBD) polypeptide”
Claim 88 recites the limitation: “The conjugate of Claim 76, comprising:… It is unclear if the CD40 antibody listed are added to the heterologous polypeptide or if it is the heterologous polypeptide. For the purpose of compact prosecution this claim has been interpreted as “"The conjugate of Claim 76, wherein the heterologous polypeptide comprises …. a CD40 antibody…..”
Claim 88 recites the limitation CD40.N2.RBDv. It is unclear what CD40.N2.RBDv is. CD40.N2.RBDv has different definitions in the specification. In the specification, the CD40.N2.RBDv is said that it can be any CD40 antibody bound to the RBD and Npep2 peptides ([0172]-[0174]). However, the CD40.N2.RBDv specifically tested in the examples has specific antigens (Table 2) and CD40.N2.RBDv only encompasses the specific antibody (anti-human CD40 12E12 hIgG4, [0227]). For the purpose of compact prosecution, the claim has been interpreted as follows: “….a CD40 antibody wherein: - the heavy chain of the antibody is fused to the Npep2 polypeptide, and - the light chain of the antibody is fused to a receptor binding domain (RBD) polypeptide;…”.
Appropriate corrections to all applicable claims are required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
6. Claims 76 and 85 are rejected under 35 U.S.C. 101 because the claims recite “nature-based products” as a limiting element or step without having markedly different characteristics than the nature-based product itself. The claimed inventions are directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application because, when the heterologous polypeptide consists of the nucleocapsid protein regions from amino acid position 1 to position 275 and from 412 to 419 fused directly (in the absence of a linker) to the Npep2 peptide consisting of the nucleocapsid protein region from amino acid position 276 to position 411, the nucleocapsid protein is reconstituted and is not markedly different from its naturally occurring counterpart because it conveys the same amino acid information and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below. See MPEP § 2106 for patent subject matter eligibility analysis.
A claim that focuses on use of a natural product must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural product itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The recent Interim Eligibility Guidance addresses the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions) – Prong 1. “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception. If yes, determine if the claim recite additional elements that integrate the judicial exception into a practical application – Prong 2. If no, proceed to step 2B.
In Step 2B determine whether the claim as a whole amounts to significantly more than the exception.
Claims 76 is drawn to a conjugate wherein a heterologous polypeptide is conjugated or fused to a polypeptide (Npep2) that derives from protein N of SARS-CoV-2 and that comprises at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2. The present claims are directed to a composition of matter so Step 1 is satisfied.
Claim 85 is drawn to the conjugate, wherein the heterologous polypeptide is fused to the Npep2 polypeptide to form a fusion protein, wherein the fusion is either direct or via a linker.
This recitation includes the heterologous polypeptide consisting of the nucleocapsid protein region from amino acid position 1 to amino acid position 275 and the region from 412 to 419 and the Npep2 peptide consisting of the nucleocapsid protein region from amino acid position 276 to amino acid position 275, wherein the nucleocapsid protein is reconstituted. See image below demonstrating this fusion protein.
QIA98613.1 nucleocapsid phosphoprotein [Severe acute respiratory syndrome coronavirus 2] amino acid sequence. https://www.ncbi.nlm.nih.gov/protein/QIA98613.1).
Npep2 polypeptide is highlighted in brown. The heterologous polypeptide fused to Npep2 consist of the unhighlighted amino acids.
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As such, the instant claims 76 and 85 recite judicial exceptions in the form of a natural phenomenon (product of nature) (Step 2A, Prong 1- YES).
The core of the claims is the nucleocapsid protein but the instant claims do not recite any additional elements that integrate this judicial exception into a practical application. Rather, the instant claims merely recite natural product as discussed above. As such, the instant claims do not recite additional elements that integrate the judicial exception into a practical application (Step 2A, Prong 2- NO).
The claimed nucleocapsid protein, is naturally occurring as demonstrated above and does not reasonably provide an inventive concept or recite any elements beyond the judicial exceptions themselves. As such, the instant claims do not recite any additional elements that amount to significantly more than the judicial exception (Step 2B- NO).
Accordingly, claims 76 and 85, do not constitute patent eligible subject matter under 35 U.S.C. § 101.
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 76, 78, 85, 88-91 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming.
The instant claims above are drawn to a heterologous polypeptide that is conjugated or fused to a polypeptide (Npep2) derived from protein N of SARS-CoV-2 comprising at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2. This conjugate recited above encompasses a genus of Npep2 peptides. Claims 78, 85, 88-91 depend on claim 76 but do not materially limit the genus of Npep2 peptides. Claim 91 is drawn to a vaccine composition that comprises the conjugate of claim 76. It is the only claim that recites a function for the conjugate: a vaccine.
When one goes to the specification to identify a representative species of this genus, it seems as if Applicant has only provided one Npep2 peptide (f-Npep2) associated with CD40.N2.RBDv to represent the genus of Npep2 peptides claimed in the instant application. This species, or even just a few species, is not sufficient to represent such a broad genus.
Even if the prior art is aware of additional Npep2 variants the totality of known variants (and in the case of instant claim 91, that would also meet the required vaccine function) would not be representative of each the genus for the reasons discussed below.
“[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.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics (vaccine) when coupled with a known or disclosed correlation between function (vaccine as per instant claim 91) and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
MPEP § 2163 states that 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, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics (vaccine) coupled with a known or disclosed correlation between vaccine function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which the Npep2 peptide comprises at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2., one must describe a sufficient variety of species to reflect the variation within the genus. However, only one peptide is provided, with the singular peptide therefore representative of the substantially large claimed genus of potential Npep2 peptides. Yet, one of skill in this art cannot envision the structure of any other Npep2 peptide, other than those taught by Applicant. There is no guarantee there are many others. There is no way to predict which mutation or length may occur. There is equally no way to know if such a mutation(s) or which peptide length would still be able to function as a vaccine as required in instant claim 91. All this requires guidance by Applicant or future research to uncover. The future does not provide written description for this application and so Applicant and the prior art are the only sources of such Npep2 peptides. As for specific species, Applicant only provides explicit teaching of such. Thus, PHOSITA can only envision the structure of the species taught by Applicant and would only consider Applicant in possession of the same, no more. Therefore, since only one species, or very few, are provided to represent the genus recited, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims (instant claim 91) can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011).
In the case of instant claim 91, for a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010). Since the peptide structure is responsible for its antigenicity and tumor-specificity, and said structure varies between T-cell epitopes, there is no correlation between structure and function between the members of such a large T-cell epitope genus as currently recited. The group need have no common structure at all. Thus, functional language should not be used to define the genus. Rather, structure should be used.
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genera. Fourteen highly similar and related species is certainly not adequate just as the related species of Joe-9 derivatives above were inadequate.
Since only possibly one related species of Npep2 peptide is taught, the instant claims above clearly fail the written description requirement. A representative number of species has not been taught to describe the genus of polynucleotides encoding such peptides. The genus is very large and would encompass many peptides encoding the same that cannot be visualized from the prior art or instant disclosure. Any future structure may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the recited genus. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As discussed above, an applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, or representative number of species, the specification does not provide adequate written description of the claimed genus.
Claims 76, 78, 85, 88-91 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 a vaccine consisting of one CD40 antibody (12E12) fused to the Npep2 peptide consisting of the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2, it does not reasonably provide enablement for any vaccine with a heterologous peptide and an Npep2 that derives from protein N of SARS-CoV-2 and that comprises at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The instant specification fails to provide information that would allow the skilled artisan to fully practice the instant invention without undue experimentation.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a heterologous polypeptide that is conjugated or fused to a polypeptide (Npep2) derived from protein N of SARS-CoV-2 comprising at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2.
The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims comprise limitations which are extremely broad, especially in light of the indefiniteness issues noted supra, as there are a large potential number of “heterologous polypeptides” which may be conjugated to the equally large number of Npep2 polypeptides. Even with the elected invention, the breadth is still large as the Npep2 peptide is drawn to a peptide with 90% identity to the region noted in SEQ ID NO:2, the anti-CD40 antibody can be any known antibody against CD40, and the receptor binding domain (RBD) can be any RBD of any protein. Even with the narrowed limitation of RBD in claim 89, there is still a large amount of breadth with the percent identity claimed to the fragment of SEQ ID NO: 3. Applicant additionally claims that the claimed conjugates can be used as vaccines.
State of the prior art/Predictability of the art. It is noted that the vaccine art is unpredictable, requiring each embodiment to be individually assessed for physiological activity in preventing diseases. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since it would require undue experimentation to generate all of those potential peptides fused to all those potential heterologous polypeptides and identify which heterologous polypeptides or Npep2 variants would be useful in an immunogenic composition, such as a vaccine, as it is not known how the conjugates will fold, if aggregates may form, if the Npep2 variants will still maintain the same epitopes, etc.
Working examples. Only one working example seems to be disclosed in the specification, namely wherein the f-Npep2 peptide is fused to the RBD(SA)var and specific CD40 antibody (CD40.N2.RBDv, noted as the Anti-CD40.COVID-19 construct “CD40.N2.RBDv” with 1 peptide (ViralSARS-CoV-2 Npep2) on the heavy chain (hAnti-CD40VH3-LV-hIgG4H) and 1 peptide (ViralSARS-CoV-2 Spike-RBDSA VAR) on the light chain (hAnti-CD40VK2-LV-hIgGK))(Table 2; ¶[0230-0265]). No other variants or mutants of Npep2 were provided or tested; no other variant or mutant proteins aside from the specific CD40 antibody and specific spike protein RBD variant were fused to the specific Npep2 construct. Therefore, only one example of the Npep2 construct that is encompassed by the breadth of the elected invention is provided for in the specification.
Guidance in the specification. The specification does not provide sufficient guidance towards identifying which characteristic of the claimed conjugates will function effectively as protein conjugates or vaccines. Especially with respect to the antibody of claim 88, it is unclear what Npep2 can be bound to what CD40 antibody and what RBD can be bound to said same antibody and still function as an “antibody”. It is unclear if the percent identities claimed with respect to the Npep2 and RBD peptides will still formulate antigenic proteins, if said proteins will fold properly, if they will aggregate in solution, or if they will fuse to any CD40 antibody and allow the proper formation of said antibody with the same claimed peptide variants attached.
Amount of experimentation necessary. Additional research is required in order to determine whether or not the breadth of the claimed peptides would effectively form conjugates, and additional research would be required to determine their effectiveness as antibodies and/or as vaccines.
In light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality. In the instantly claimed invention, it would be necessary to practice the invention for a person skilled in the art to design and conduct an exhaustive amount of complex experiments to demonstrate that the claimed conjugates could not only be formulated, but also still retain aspects of their claimed functions (e.g. “antibodies” against CD40 and domains which could bind to receptors), as well as be administered to a subject as vaccines. The extremely large amount of experimentation required would be considered undue and burdensome.
In conclusion, Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[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”. The use of the claimed conjugates as recited in the instant claims is not enabled by the instant specification.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary.
Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 76, 78, 85, 88 and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Hashem (US 2020/164058 A1 filing date Nov. 27 , 2018 IDS dated 03/20/2023 US patent documents 1), Grifoni (Cell Host & Microbe, vol. 27, no. 4, 16 March 2020, IDS dated 03/20/2023 citation M), and QIA98613.1 (QIA98613.1 nucleocapsid phosphoprotein [Severe acute respiratory syndrome coronavirus 2], VRL 06-April-2020, https://www.ncbi.nlm.nih.gov/protein/QIA98613.1) in view of Zurawski1 (WO 2014/085580 A, publication date June 5, 2014), Zurawski2 (J. Virol. May 2017 Volume 91 Issue 9 1-20, IDS dated 03/20/2023 citation AG), Flamar (AIDS. 2013 Aug 24;27(13):2041-51), AJD85779.1 (GenBank: AJD85779.1.anti-human CD40 12E12 antibody HIV antigen fusion protein https://www.ncbi.nlm.nih.gov/protein/AJD85779.1 01/19/2015) and AJD85780.1 (GenBank: AJD85780.1, anti-human CD40 12E12 antibody HIV antigen fusion protein https://www.ncbi.nlm.nih.gov/protein/AJD85780.1 01/15/2015)
Hashem teaches a vaccine (instant claim 91) comprising a MERS-CoV S1 protein fused to a CD40 ligand polypeptide (title, abstract). CD40 is a receptor constitutively expressed on many antigen presenting cells (APCs). A ligand that binds to CD40 is CD40 Ligand or CD40L. Other ligands for CD40 that may be employed along with or instead of CD40L include antibodies or antibody fragments that activate or agonize CD40 including monoclonal antibodies and their fragments or chimeric or fully human antibodies to CD40 and their fragments [0021], (instant claims 76 and 88). MERS-CoV antigens include viral antigens encoded by the structural protein genes Spike (S), Envelope (E), Membrane (M) and nucleocapsid (N) [0044] (instant claim 76). Hashem teaches that there are several vaccine candidates based on full-length or truncated S protein including vectored vaccines, DNA vaccines, nanoparticle vaccines, S or RBD protein-based subunit vaccines [0017] (instant claims78 and 88). Hashem teaches that incorporating a CD40 ligand into this MERS-CoV S1 subunit vaccine (including the viral RBD), (instant claims 78 and 88) can enhance immunogenicity and (vaccine) efficacy [0043]. These vaccines can also include a linker [0031], [0063] and [0074], (instant claim 85).
Hashem does not teach a polypeptide derived from protein N of SARS-CoV-2 comprising at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO: 2.
Grifoni teaches the use of the Tepitool resource in IEDB (Immune Epitope Database and Analysis Resource public repository) (page 674, Prediction of SARS-CoV-2 T Cell Epitopes section). The IEDB also provides bioinformatic tools and algorithms that allow for the analysis of epitope data and prediction of potential epitopes from novel sequences (page 671, 2nd column, 2nd paragraph). Grifoni also teaches the use of The Virus Pathogen Resource (ViPR) is a complementary repository of information about human pathogenic viruses that integrates genome, gene, and protein sequence information with data about immune epitopes, protein structures, and host responses to virus infections (page 671, 2nd column, 2nd paragraph). These publicly available IEDB and ViPR resources were used to predict B- and T-cell epitopes located within the S and N protein of SARS-CoV-2 (page 671 Introduction), one of which encompasses 46 amino acids spanning residues 35-400 (table 4). This epitope region is a 91.3% match of the N protein (SEQ ID NO: 2) (that is, bigger than 90%) of the instant application (instant claims 76, 85, 88 and 91) . See sequence alignment below:
Title: US-17-927-804-2
Sequence: 1 MSDNGPQNQRNAPRITFGGP..........LDDFSKQLQQSMSSADSTQA 419
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Query Match 10.1%; Score 221; DB 1; Length 46;
Best Local Similarity 91.3%;
Matches 42; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 354 NKHIDAYKTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAAD 399
|||||||||||||||||||||| || | |||||||| |||||||||
Db 1 NKHIDAYKTFPPTEPKKDKKKKTDEAQPLPQRQKKQPTVTLLPAAD 46
QIA98613.1 teaches an amino acid sequence that is 100% identical to SEQ ID NO: 2 and comprises 50 or more amino acids (see below), (instant claims 76, 85, 88 and 91).
PNG
media_image1.png
219
927
media_image1.png
Greyscale
Zurawski1 teaches a vaccine composition (instant claim 91) comprising: a) at least a first CD40 antibody (instant claim 88) attached to at least a first influenza hemagglutinin (HA) antigen (and a flagellin) (claim 39). The HA1-1 antigen module is attached directly to the Heavy Chain (HC) C terminus ([00185]-[00187], [00189] (instant claim 88)
Zurawski2 teaches dendritic cells-targeting vaccines (instant claim 91) comprising humanized recombinant monoclonal antibodies to CD40 (instant claim 88) fused to HIV Env gp140 and these vaccines raised robust immunity against HIV-1. HIV Env gp140 protein is fused to the C-terminus of the CD40 antibody HC (page 13, Material and Methods, first paragraph), (instant claim 88).
Flamar teaches specifically the 12E12 CD40 antibody that has been used in the instant application as disclosed in the specification. Flamar also teaches that their vaccine expands memory CD4+ and CD8+ T cells specific to multiple epitopes within all five peptide regions across a wide range of major histocompatibility complex (MHC) haplotypes (abstract, results). That is, the vaccine elicit an immune response. In addition, AJD85779.1 and AJD85780.1 teach the sequences of this antibody which are 100% identical to instant SEQ ID NO: 35 (VH of 12E12) (AJD85779.1) and 100% identical to instant SEQ ID NO: 36 (VL of 12E12) (AJD85779.1). See attached for NCBI BLAST alignments.
It would be obvious for a person having ordinary skills in the art to combine the teachings of Hashem, Flamar, AJD85779.1 and AJD85780.1 with Grifoni to develop a vaccine comprising: (1) a heterologous polypeptide (that is a CD40 antibody, with or without the RBD polypeptide as taught by Hashem, this antibody being the 12E12 antibody of Flamar, AJD85779.1 and AJD85780.1 ) fused to (2) the epitope within the protein N of SARS-CoV-2 (position 276 to position 411) as taught by Grifoni. It would have further been obvious to combine Grifoni with QIA98613.1 to expand the length of the SRAS-CoV-2 N polypeptide to be at least 50 amino acids and with higher % of identity while still retaining the B- and T-cell epitopes predicted by Grifoni. The artisan would have been motivated to do so because Hashem teaches us that a CD40 antibody fused to a viral antigen (MERS-CoV virus spike protein (including the RBD)) have been used as vaccines, and Flamar, AJD85779.1 and AJD85780.1 specifically teach the exact 12E12 antibody. In addition, Zurawski1 and Zurawski12 also teach us that a CD40 antibody can be fused to a viral antigen (an HIV protein or a Flu protein) and be used as vaccines. Therefore, the artisan would be motivated to fuse a CD40 antibody (including the 12E12) with SARS-CoV-2 viral epitopes (Npep2 variant as taught by Grifoni and QIA98613.1 and/or an RBD polypeptide as taught be Hashem). There would be a reasonable expectation of success because Zurawski1, Zurawski2, Hashem and Flamar have been successful eliciting an immune response with their vaccines and the CD40 receptor (bound by the CD40 antibody, 12E12, or CD40L) is expressed on APC (as taught by Hashem) and plays a crucial role in immune responses and such vaccines can enhance immunogenicity and efficacy as taught by Hashem.
It would further be obvious that the CD40 antibody would be fused to the viral antigen by its C terminus as taught by Zurawski1 and Zurawski12 (instant claim 76 requires a Npep2 variant to be a part of the instant invention) and any additional epitope added to this conjugate that already included the Npep2 variant would need to be linked to the antibody’s light chain (for instance the RBD polypeptide).
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 76, 78, 88-90 are rejected under 35 U.S.C. 103 as being unpatentable over Hashem, Grifoni, QIA98613.1, Zurawski1, Zurawski2, Flamar, AJD85779.1 and AJD85780.1 in view of Aurisicchio (US 2023/0285540 A1, Priority date April 30, 2020), Naveca (SARS-CoV-2 reinfection by the new Variant of Concern (VOC) P.1 in Amazonas, Brazil - SARS-CoV-2 coronavirus _ nCoV-2019 Genomic Epidemiology – Virological. https://virological.org/t/sars-cov-2-reinfection-by-the-new-variant-of-concern-voc-p-1-in-amazonas-brazil/596 posted online January 17, 2021. See attached PDF) and Estep (SARS-CoV-2 (2019-nCoV) vaccine, White-Paper-SARS-CoV-2-vaccine-ver-3-3-0.pdf, Pages 1-69, https://radvac.org/wp-content/uploads/2020/11/White-Paper-SARS-CoV-2-vaccine-ver-3-3-0.pdf November 6, 2020 )
Hashem, QIA98613.1, Grifoni, Zurawski1, Zurawski2, Flamar, AJD85779.1 and AJD85780.1 teachings have been discussed above and incorporated herein.
Aurisicchio teaches the SARS-CoV-2 RBD polypeptide which is 100% identical to the amino acid residue at position 319 to the amino acid residue at position 541 in SEQ ID NO:3 (instant claims, 76, 78 and 88-89). See sequence alignment below.
Title: US-17-927-804-3_COPY_319_541
Sequence: 1 RVQPTESIVRFPNITNLCPF..........ATVCGPKKSTNLVKNKCVNF 223
US-17-997-527A-13
Sequence 13, US/17997527A
Publication No. US20230285540A1
GENERAL INFORMATION
APPLICANT: TAKIS SRL
TITLE OF INVENTION: Polynucleotides encoding antigens of SARS-CoV-2 and their use inmedical field as vaccines
FILE REFERENCE: PCT44884
CURRENT APPLICATION NUMBER: US/17/997,527A
CURRENT FILING DATE: 2022-10-28
PRIOR APPLICATION NUMBER: IT 102020000009625
PRIOR FILING DATE: 2020-04-30
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 13
LENGTH: 224
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: amino acid sequence of SARS-CoV-2 RBD
Query Match 100.0%; Score 1211; Length 224;
Best Local Similarity 100.0%;
Matches 223; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFK 61
Qy 61 CYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 CYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNS 121
Qy 121 NNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 NNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQ 181
Qy 181 PTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNF 223
|||||||||||||||||||||||||||||||||||||||||||
Db 182 PTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNF 22
Aurisicchio does not teach mutations K417T, E484K, N501Y and C538S.
Naveca teaches that the lineage P.1 (alias of B.1.1.28.1) is an emerging variant that harbors several amino acid mutations in the spike protein including K417T, E484K, and N501Y (Summary), (instant claim 90).
Naveca does not teach the C538S mutation in the spike protein.
Estep teaches that multiple substitutions were made to circularize, to enhance solubility, and to provide a stabilizing salt bridge present in the full Spike. One of them being Cysteine 538 that was substituted with Serine (C538S), (page 68 first paragraph), (instant claim 90).
It would be obvious for a person having ordinary skills in the art to combine the teachings of Hashem, Grifoni, QIA98613.1, Zurawski1 and Zurawski2 as explained in detail above to generate a vaccine comprising a CD40 antibody with an Npep2 variant and an RBD polypeptide, which specifically incorporates in the conjugate polypeptide the SARS-CoV-2 RBD polypeptide (319 to 541) taught by Aurisicchio. The artisan would have been motivated to do because Aurisicchio’s SEQ ID NO: 13 is 100% identical to instant SEQ ID NO: 3 and therefore the sequences have the same characteristics. There would be a reasonable expectation of success because the molecular biology techniques needed to create such a conjugate polypeptide are standard techniques easily reproducible.
It would further be obvious to incorporate the K417T, E484K, N501Y and C538S mutations in Aurisicchio’s SEQ ID NO: 13 to develop a vaccine targeting a specific SARS-CoV-2 variant or strain. In addition, the incorporation of C538S substitution can help stabilize a spike protein based vaccine. The artisan would have been motivated to do so because K417T, E484K, N501Y are found in highly infective variants and C538S mutation reduces this intrinsic propensity for aggregation, allowing the protein to form more stable, uniform monomers. There would be a reasonable expectation of success because introducing such mutations would just require standard molecular techniques and there is a need to develop more effective stable vaccines targeting highly infectious variants/strains originated by the high mutation rate of SARS-CoV-2.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 76, 85 and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-25, 28 and 37 of copending application No. 18/710,734. The reference is not afforded safe harbor protection under 35 USC 121 because it does not share continuity with much less is it subject to a restriction/speciation with the instant application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the genus of a heterologous polypeptide fused to a Npep2 variant is claimed in 17/927,804 and 18/710,734 is a species of the genus. Both, the claims of 18/710,734 and the claims of 17/927,804 are drawn to a conjugate, wherein a heterologous polypeptide is conjugated or fused to a polypeptide (Npep2) that derives from protein N of SARS-CoV-2 and that comprises at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 in SEQ ID NO:2 and a vaccine comprising the conjugate.
The Npep2 SEQ ID NO: 2 of 17/927,804 and the Npep2 SEQ ID NO:1 of 18/710,734 are 100% identical (see below) and the heterologous polypeptide of 17/927,804 can comprise all the polypeptides fused to Npep2 of 18/710,734.
Title: US-17-927-804-2
Sequence: 1 MSDNGPQNQRNAPRITFGGP..........LDDFSKQLQQSMSSADSTQA 419
Database : US-18-710-734-1.pep:*
SUMMARIES
Result % Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 2194 100.0 419 1 US-18-710-734-1 UNIVERSAL SARBECOV
ALIGNMENTS
US-18-710-734-1
Query Match 100.0%; Score 2194; DB 1; Length 419;
Best Local Similarity 100.0%;
Matches 419; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHG 60
Qy 61 KEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAG 120
Qy 121 LPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGS 180
Qy 181 QASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQ 240
Qy 241 QQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 QQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKH 300
Qy 301 WPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAY 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 WPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAY 360
Qy 361 KTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA 419
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQQSMSSADSTQA 419
Therefore, the instant application claims are anticipated by the copending application claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/RACHEL B GILL/Primary Examiner, Art Unit 1671