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 09/21/2023 been entered. Claims 1-17 are pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) submitted on 09/21/2023 has been considered by the examiner.
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 March 23, 2021 based on the filing date of the KR10-2021-0037160 application.
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/PatentLegalFramework), 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 – 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:
i) the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in 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 of the material 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.
Objections
Specification
1. 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are:
[0056] In yet another embodiment of the present invention, the quick exchange technique was used to be manipulated to express various CD4+ and CD8+ T cell epitopes in fusion with the attenuated reovirus σ1 protein.
[0059] an amino acid sequence of an epitope of an antigen causing cancer or an infectious disease
[00110] A reverse genetics system for the reovirus was transfected with 10 viral gene segments and a T7 expressing cell line to generate replicable reovirus particles.
[00120] Furthermore, as a result of performing the dot blot method on the cell lysate obtained by infecting the L929 cells, as shown in FIG. 3C, it was confirmed that the recombinant RBD is expressed by the SARS-CoV-2 neutralizing antibody (NeuAb) (top) and anti-reovirus antibodies (bottom).
See also Claim Rejections - 35 USC § 112(b). Applicant is also requested to correct all similar indefinite language found in the specification.
2. The disclosure is objected to because of the following informalities:
a) The use of the term(s), e.g., Alexa Fluor® , Fluoromount-G® and PER.C6 which are a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, and/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 ‘Alexa Fluor®’, PER.C6® and Fluoromount-G®´ are merely examples and all improper uses of trademarks in the specification should be identified by applicant and properly addressed.
Appropriate correction is required.
Drawings
The drawings are objected to because the specification discloses “As a result, as depicted in FIG. 5, fluorescence (red) from the Myc and FLAG tags in cases infected with ReoV+OVA257-264 overlapped with the fluorescence (green) detected for the reovirus protein” [0129]. Color cannot be referenced in black and white pictures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 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.
4. Claims 1-17 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
Claims 1 and 15 recite the limitation "….epitope of an antigen causing cancer or an infectious disease,….”. It is unclear what it is meant by this limitation since antigens do not cause cancer or infectious diseases. For the purpose of compact prosecution this limitation has been interpreted as “viral or tumor (cancer) antigens”.
Claim 2 recites the word “…represented by….” It is unclear what it is meant by this limitation. For the purpose of compact prosecution this limitation has been interpreted as “consists of”.
Claim3 recite the word “…represented by….” It is unclear what it is meant by this limitation. For the purpose of compact prosecution this limitation has been interpreted as “encoded by”.
Claims 3, 9 and 15 recites the phrase “….base sequence…..." It is unclear what it is meant by this limitation. For the purpose of compact prosecution this limitation has been interpreted as “nucleotide sequence”.
Claim 5 recites the limitation “….selected from the group consisting of a linker (SEQ ID NO: 11), Myc protein (SEQ ID NO: 12), FLAG protein (SEQ ID NO: 13), and 2A peptide, both before and after the amino acid sequence of the epitope.”. The group consist of 4 sequences but the word “both” is used instead and is unclear what “both” refers to. It is also unclear if only the 2A peptide is to be both before/after the epitope or if any of the items identified in the Markush group (linker, Myc, Flag proteins and 2A peptide) are intended to be before/after the epitope. Claim 5 also recites the limitation “….further comprising one or more amino acid sequences….” It is unclear if this “one or more sequences” are BOTH inserted before or after or before and after.
Claim 7 recites a mixed list of infectious diseases and infectious agents. The recitation is unclear because it should be the infectious disease and then either a list of said infectious diseases (e.g. COVID, infantile enteritis, gastroenteritis, etc.) OR it should be a pathogen which causes infectious disease, and then ONLY list the pathogens. One of these two options need to be selected and the recitation needs to be consistent with this selection. The preferred selection would be infectious disease caused by a pathogen selected from the group consisting of SARS CoV-2, Hepatitis C, Influenza, etc.
Claim 13 recites the limitation “A vaccine composition based on attenuated reovirus,…” This language is unclear. For the purpose of compact prosecution this limitation has been interpreted as follows: “An attenuated reovirus vaccine composition, wherein the active ingredient in said composition comprises the polypeptide of claim 1, a polynucleotide which encodes the polypeptide of claim 1, or a viral vector comprising the polynucleotide which encodes the polypeptide of claim 1.”
Claim 15 recites the limitation “….based on the attenuated reovirus…. “ The use of the definite article “the” is unclear as it implies a reference back to something specific. The preamble of claim 15 can be clarified by either using “an attenuated reovirus” or by using “the attenuated reovirus of claim 1”. In addition, claim 15 recited the limitation “….a) preparing a reverse genetics virus vector comprising a base sequence encoding an attenuated reovirus σ1 protein represented by SEQ ID NO: 1; and b) introducing a polynucleotide into the vector, wherein the polynucleotide encodes an attenuated reovirus σ1 protein and an epitope of an antigen….”. This limitation is unclear because it reads as if the sequence encoding an attenuated reovirus σ1 protein is comprised in step a) but also it is introduced in step b). For the purpose of compact prosecution this limitation has been interpreted as follows: “….generate a reverse genetics virus vector by introducing a polynucleotide into the vector, wherein the polynucleotide encodes SEQ ID NO: 1 and an epitope of an antigen,,,,.”. Additionally claim 15 recites the limitation: “….by substituting or inserting a base at positions 763 to 1416….” It is unclear what the term “base” refers to. For the purpose of compact prosecution this limitation has been interpreted as follows: “….by substituting or inserting said polynucleotide of step b) at positions 763 to 1416 of the wild type σ1 nucleotide sequence”.
Claim 16 recites the limitation “….comprising the step of c) producing and proliferating the vector based on the attenuated reovirus comprising the polynucleotide from the step b) in one or more cell selected from….”. This step is confusing because the method of producing the vector is described in claim 15. In addition, since the claims recites “one or more”, the term “cells” should be in plural. For the purpose of compact prosecution this limitation has been interpreted as “….comprising the step of transfecting the reverse genetic virus vector of claim 15 in one or more cells selected from….”.
Claims 1-17 are rejected for claiming the limitation of amino acids (1 to 250th amino acid) or nucleotide positions (positions (763 to 1416) within a corresponding protein or nucleotide sequences without providing an appropriate frame of reference for said protein or nucleotide sequence. Said frame of reference can be provided by referencing a sequence disclosed within the application (i.e. a sequence with a SEQ ID NO: identifier) or by referencing a start position for said sequence (i.e. “…wherein said nucleotide is at position X from the starting ATG of the open reading frame…” or “…wherein said amino acid is at position X from the starting methionine of the protein…”). Claim 9 recites the limitation “sequence encoding the epitope is substituted or inserted at positions 763 to 1416 of from the 5' end of ….”. This limitation is unclear because there is no SEQ ID NO as a frame of reference for the positions cited.
Appropriate corrections are required. Applicant is also requested to correct all similar indefinite language found in the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 4 depends on claim 1 but it is not adding any new limitations to claim 1. Claim 1 already recites a fusion protein at the carboxy-terminus of the attenuated reovirus σ1 protein.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-17 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.
Claim 1 recites “a polypeptide comprising an amino acid sequence of an attenuated reovirus σ1 protein; and an amino acid sequence of an epitope of an antigen causing cancer or an infectious disease, wherein the polypeptide comprises the 1 to 250th amino acid sequence of the attenuated reovirus σ1 protein truncated at the 251st amino acid position from the N-terminus; and an amino acid sequence of an epitope of an antigen causing cancer or an infectious disease inserted at the amino acid position including and subsequent to the 251st from the N-terminus of the amino acid sequence of the attenuated reovirus σ1 protein.”. This polypeptide is capable of curing and preventing cancer or an infectious disease, which encompasses a genus of agents. Claims 2-17 are dependent from Claim 1 and do not materially limit the genus of agents, especially regarding the nature of the fusion polypeptide (SEQ ID NO: 1 truncated at the 251st amino acid position from the N-terminus and fused to a viral or cancer epitope) (or corresponding nucleic acid sequences: SEQ ID NO: 2 followed at its 3’ end by a viral or cancer epitope nucleotide sequence) and are therefore included in the rejection). These claims do not require that the genus of the claims possess any particular structure or other distinguishing feature that is characteristic of the genus as a whole. Therefore, the claims are drawn to a genus of “a truncated σ1 fused to a viral or tumor epitope” for which there is inadequate written description.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), 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 applicant was in possession of the claimed genus MPEP 2163(II)(3)(a)(i)(C).
In the instant case, the only identifying characteristic present in the claim is a recitation of requisite activity (capable of curing and preventing cancer or an infectious disease There is not even identification of any particular portion of a structure that must be conserved for said activity. It is not clear that such a fusion protein would be stable or immunogenic, or what additional items (e.g. linkers, 2a sites, etc.) would be required to promote expression or immunogenic function. Regarding the genus of the claims the specification describes eight specific species within the genus claimed (Specification [Table 2]) and ReoV+RBD (Reo-RBD) was used to check for expression. From the specification, it is clear that Applicant is in possession of species of ReoV+RBD (Reo-RBD), ReoV+OVA257-264, REOV+p15E and ReoV-S21P2(2) and the expression of some of the fusion polypeptide was confirmed by the dot blot technique (Specification [00116-00139]). The claims, however are not limited to those species but also includes any viral or tumor epitope, and the specification fails to provide a representative number of species within the recited genus. All the σ1 protein sequences that would reasonably go into making the chimeric/fusion protein have not been tested,
Functionally defined genus claims 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).
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.
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 epitopes have not been defined, one must describe a sufficient variety of species to reflect the variation within the genus. Yet, one of skill in this art cannot envision the structure of any other antigen peptide, other than those taught by Applicant. There is no guarantee there are many others. There is no way to predict which changes may occur. There is equally no way to know if such fusion polypeptides would still be able to function as vaccines, even if the fusion polypeptide is expressed as shown by the dot blot technique, and cure or prevent cancer or infectious diseases. All these experiments requires guidance by Applicant or future research to uncover. 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.
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.
Claim 12-13 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 isolated or purified vector or nucleic acid does not reasonably provide enablement for said non-isolated vector or nucleic acid which reads upon a transgenic animal or a transgene therein. 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/or use the invention commensurate in scope with these claims.
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. Applicant broadly claims a vector or nucleic acid. Under broadest reasonable interpretation, the claims read on a cell within a transgenic animal or a transgene therein, given that the term "isolated" is not denoted in describing the host cell, nucleic acid, or vector.
State of the prior art/Predictability of the art. With respect to the unisolated host cells and transgenes as “nucleic acids” or “vectors “of the instant claims discussed above, the state of the art at the time of filing was such that one of skill in the art could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene and possible silencing of host genes, which result in undesirable phenotypes and/or additional health issues in the animal. The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene in the host. Viral vectors, such as Adeno-associated virus (AAV), adenovirus (AdV), and lentiviral/retroviral vectors, can transfer larger amounts of genetic information to a host, but some vectors cannot carry all the required genetic structures for proper expression (e.g. entire gene plus extensive regulatory elements) and certain viral vectors can cause uncontrolled, random integration, which increases the risk of tumorigenesis and inconsistent expression. (See e.g. National Academies of Sciences, Engineering, and Medicine; Division on Earth and Life Studies; Food and Nutrition Board; Board on Agriculture and Natural Resources; Committee on Heritable Genetic Modification in Food Animals. Heritable Genetic Modification in Food Animals. Washington (DC): National Academies Press (US); 2025 Apr 23. 3, Potential Hazards to Animals and Consumers.; Park F. Lentiviral vectors: are they the future of animal transgenesis? Physiol Genomics. 2007 Oct 22;31(2):159-73. Epub 2007 Aug 7.; Shakweer WME, Krivoruchko AY, Dessouki SM, Khattab AA. A review of transgenic animal techniques and their applications. J Genet Eng Biotechnol. 2023 May 9;21(1):55.). Therefore, the field of transgenics was and remains highly unpredictable.
Working examples/Guidance in the Specification. No working example of a transgenic animal is disclosed in the specification. The specification provides guidance towards the generation and use of an isolated/purified vector or nucleic acid.
Amount of experimentation necessary. At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to clarify that the vector or nucleic acid is not within a transgenic animal by utilizing the term "isolated" before the recitation of said vector or nucleic acid. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use the transgenes and transgenic animals commensurate in scope with the claimed invention with a reasonable expectation of success. Thus, the claims are rejected here.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make and/or use the claimed products.
Claims 1-17 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 (1) ReoV+RBD (Reo-RBD), ReoV+OVA257-264, REOV+p15E and ReoV-S21P2(2) (expressing SARS-CoV-2 linear B cell epitope) fusion proteins and (2) the expression or detection of SARS-CoV-2, and SARS-CoV-2 linear B cell epitope can induce an specific immune response against the specific epitope (see below), does not reasonably provide enablement for (1) any σ1-fused to any viral or tumor epitope and does not reasonably provide enablement for (2) prevention of any cancer or any infectious disease. 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. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claims 1-17 of the instant application are drawn to a polypeptide comprising an amino acid sequence of an attenuated reovirus σ1 protein; and an amino acid sequence of an epitope of an antigen causing cancer or an infectious disease, wherein the polypeptide comprises the 1 to 250th amino acid sequence of the attenuated reovirus σ1 protein truncated at the 251st amino acid position from the N-terminus; and an amino acid sequence of an epitope of an antigen causing cancer or an infectious disease inserted at the amino acid position including and subsequent to the 251st from the N-terminus of the amino acid sequence of the attenuated reovirus sigma- 1 protein. A vaccine composition comprising the polypeptide that can be used for preventing or treating cancer or an infectious disease and a method of preventing any cancer or any infectious disease in a subject, Therefore, the invention encompasses a vaccine comprising the polypeptide of claim 1 to be used for preventing disorders such as any type of cancer and any infectious disease.
Breadth of the claims: The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims that the instant vaccines can be used prevent any cancer or any infectious infection. Thus, the cited claims are deemed very broad since these claims read on essentially preventing any type of cancer in any subject comprising the administration of the claimed vaccines which includes subjects at risk of developing any type of cancer. In addition, the cited claims are deemed very broad since these claims also read on essentially preventing any type of viral diseases.
State of the Prior Art: While the state of the art with regard to the treatment of cancer or viral infections is relatively high, the state of the art with regard to the prevention of cancer is underdeveloped. This is because there would be no way to determine that cancer would have predictably occurred without treatment. In the case of infectious diseases, vaccination has shown to prevent specific diseases when the vaccines are developed to target specific pathogens but currently no known platform to generate vaccines has been shown to be successful in developing vaccines for all types of infectious agents.
Regarding prevention of cancer, the American Cancer Society maintains that “There's no sure way to prevent cancer, but you can help reduce your risk by making healthy choices like eating right, staying active, and not smoking” (American Cancer Society. Cancer Risk and Prevention. https://www.cancer.org/cancer/risk-prevention.html).
Regarding prevention of any infectious disease, the art establishes that vaccines work by stimulating the body’s immune system to recognize specific pathogens, but not all pathogens can be recognized by the same vaccine or even different vaccines created using the same vaccine platforms (either attenuated viruses, mRNA, antibodies or T-cell epitopes etc.). Infection by a pathogen induces an adaptive immune response by T cells that is specific for defined pathogen epitopes. (Soethout. Identifying the epitope-specific T cell response to virus infections. Vaccine 25 (2007) 3200–3203, Abstract) and out of many viral epitopes that can be displayed only a few elicit measurable T cell responses, a phenomenon known as immunodominance (Introduction). Chen (Expert Opin. Biol. Ther., Vol. 13, No. 5, Pg. 657-671, 2013) teaches that anti-HIV antibodies could help eradicate HIV-1 but that development of vaccine immunogens capable of eliciting such antibodies in humans remains a fundamental challenge (Abstract). Thus, there is no vaccine recognized to date that can prevent HIV infection, which in part would be owed to antibody-based immune responses. However, antibodies against RSV infection have been approved by the FDA for infants 6 months or older. In other words, antibodies may sometimes be effective for prevention but in other cases antibodies may not be and this is mostly because of the specific viral life cycle. Therefore, there is reasonable expectation that a vaccine produced to target SARS-CoV-2, may not prevent HIV infection or infections by other unrelated viruses.
Together with the evidence discussed above, a vaccine composition based on attenuated reovirus, comprising as an active ingredient, the polypeptide of claim 1 would not predictably prevent all pathogen infections nor would it reliably prevent infections caused by SARS-CoV-2, for example, in every single case.
Predictability/Unpredictability in 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 one skilled in the art would recognize that the recitation encompasses the prevention of any cancer and prevention of any viral infection. Thus, the skilled artisan would view that the prevention of any cancer or viral infection encompassed by the claims, (by administering to the subject a composition based on attenuated reovirus, comprising as an active ingredient, the polypeptide of claim 1, a polynucleotide encoding the same, or a virus vector comprising the polynucleotide encoding the same), is highly unpredictable.
Guidance of the Specification/Working Examples: Applicant is enabled for the ReoV+RBD (Reo-RBD), ReoV+OVA257-264, REOV+p15E and ReoV-S21P2(2) fusion proteins. Applicant has not provided any working examples suggesting that the vaccines comprising the claimed fusion proteins may induce a specific immune response against a specific epitope. Applicant has only mentioned in the Specification that previous studies have verified that the SARS-CoV-2 linear B cell epitope produces neutralizing antibodies (Poh et al., Nat Commun. 2020 Jun 1;11(1):2806) [00132] but these studies were not conducted with the fusion proteins or testing additional epitopes. Thus, the specification fails to provide sufficient evidence in support of prevention of any type of cancer or any type of viral disease as recited in the instant claims.
Additionally, the examples provided do not demonstrate the prevention of any type of cancer or infectious disease. Additionally, the disclosure does not discuss, or demonstrate through working examples, a method that could be used to determine that recurrence of diseases/disorders was prevented using the claimed agents as there is no disclosed method to determine that recurrence of any cancer would have predictably occurred without treatment.
The Quantitation of Experimentation Required: In order to practice Applicants invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments, including expansive clinical trials, needed to use the invention based on the content of the disclosure, to demonstrate that the claimed compounds could be administered to a subject to prevent cancer or an infectious disease. The population of subjects could include any subject, and thus the quantitation of experimentation is unreasonably large. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome. In the instantly claimed invention, the breadth of the different possible vaccines would cause a skilled artisan to have to perform an undue amount of experimentation on such extremely large amount of possible vaccines in order to determine if any such vaccines would be enabled for prevention of any cancer or any infectious diseases.
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 prevention of cancer and infectious diseases is not enabled by the instant specification.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
2. Claim 1, 4-6, 9-10, 12-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kemp (Cancer Gene Therapy (2019) 26:268–281).
Kemp teaches that one of the approaches to increase the anti-cancer potency of oncolytic viruses (such as Reovirus) is through incorporating therapeutic transgenes in the virus backbone (instant claim 1, 6 and 14). Genetic modification of dsRNA viruses can be challenging but the development of a plasmid-based reverse genetics system (instant claim 15) has allowed researchers worldwide to make adaptations to the reovirus genome (page 268, second column third paragraph). In addition, recombinant reoviruses expressing a truncated σ1 spike fused to a small transgene such as iLOV, UnaG, E4orf4, and GM-CSF have been demonstrated the feasibility of such platform and these viruses all seemed potent cancer-killing viruses, (page 278, second column, first paragraph).
The S1 segment-encoded head domain of the reovirus σ1 protein was replaced for the small fluorescent protein iLOV page 268, second column third paragraph). Kemp also teaches the generation of other recombinant reoviruses constructs expressing fusion proteins such as rS1-E4orf4 (the S1 head domain was replaced for a gene encoding E4orf4. (Adenovirus-derived protein E4orf4 functions as a multifunctional viral antigen (instant claim 1) is involved in the induction of tumor-cell selective non-classical apoptosis), and rS1-mmGMCSF and rS1-hsGMCSF which harbor the codons for murine or human GM-CSF, respectively (GM-CSF is widely used to generate dendritic cells in vitro), (page 269 first column first and second paragraph). The Plasmid constructs, the Recombinant reovirus sections and Fig. 1 (page 270) describe how the rS1-mmGMCSF and rS1-hsGMCSF were constructed (instant claims 12-16 and Fig 2 in the specification depicts the reovirus reverse genetics system and the process of reovirus proliferation). The plasmid constructs comprise: the nucleotides 1-768 of the reovirus S1 segment (instant claim 9), including the 5′ UTR, the codons for the first 252 amino acids of σ1 protein, the P2A peptide sequence and a transgene (instant claims 1, 4, 5, 9 and 12-14). This reads on a recombinant DNA plasmid vector (polynucleotide and virus vector) capable of expressing a polypeptide comprising an amino acid sequence of an attenuated reovirus σ1 protein (truncated at about the 251st amino acid position); and an amino acid sequence of a transgene. Along with the Plasmid constructs section, the Recombinant reovirus section teaches the method of rescuing the plasmid constructs rS1-mmGMCSF and rS1-hsGMCSF by transfecting them alongside other plasmid containing reovirus essential genes in BSR-T7 cells to be able to form and grow recombinant reovirus particles (instant claim 15-16) The data obtained in a murine model of pancreatic cancer (instant claim 6) demonstrated a systemic increase in DC and T-cell activation (that is, inducing cell-mediated immunity) upon intratumoral administration of rS1-mmGMCSF. These data demonstrate that reoviruses expressing functional GM-CSF can be generated and have the potential to enhance anti-tumor immune responses. The GM-CSF reoviruses represent a promising new agent for use in oncolytic virotherapy strategies (abstract). That is, any transgene capable of enhancing an immune response can be fused to the truncated σ1 protein and can be used for cancer treatment or viral infection treatment (reovirus with S1 carrying a transgene coding for the adenovirus-derived apoptotic E4orf4 protein, a viral antigen), (instant claim 10, 14 and 17).
Fig. 1: Structure of the S1 segments in the various recombinant reoviruses.
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Therefore, the reference teachings anticipate the claimed invention.
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 1, 4-7, 9-11, 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp in view of Sanchez-Trincado (Journal of Immunology Research, Volume 2017, Article ID 2680160, 1-14).
Kemp teachings have been described above and incorporated herein.
Kemp does not teach the epitope to be selected from the group consisting of CD4+ T cell, CD8+ T cell, and B-cell epitopes.
Sanchez-Trincado teaches that identifying epitopes in antigens is of great interest for a number of practical reasons, including understanding disease etiology, immune monitoring, developing diagnosis assays, and designing epitope-based vaccines (entire article, page 2, first column last paragraph). Traditional epitope identification has depended entirely upon experimental techniques, being costly and time-consuming. Thereby, scientists have developed and implemented epitope prediction methods that facilitate epitope identification and decrease the experimental load associated with it (page 3, second column first paragraph). T-cell epitope prediction aims to identify the shortest peptides within an antigen that are able to stimulate either CD4 or CD8 T-cells (page 2, second column second paragraph), (that is, inducing cell-mediated immunity). B-cell epitope prediction aims to facilitate B-cell epitope identification with the practical purpose of replacing the antigen for antibody production (page 6, first column third paragraph), (that is producing neutralizing antibodies) as required by instant claims 10-11.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Kemp and Sanchez-Trincado to create a vaccine composition comprising a polypeptide (the corresponding nucleotide sequence and a virus vector comprising said polynucleotide) comprising an attenuated reovirus σ1 protein; truncated at about 252st amino acid position from the N-terminus; and a transgene. This transgene can be an amino acid sequence of an epitope of an tumor or viral antigen (epitopes taught by Sanchez-Trincado). One of ordinary skill would have been motivated to do so because Kemp teaches a platform comprising viruses with a truncated σ1 spike and a transgene capable of enhancing an immune response (needed for cancer or viral infection treatments) and Sanchez-Trincado teaches tools to easily identified potential T cell or B cell epitopes that could be used as the transgenes that are part of the fusion “truncated σ1-epitope (transgene)” polypeptide.
It would further be obvious that the type of cancer or infectious disease to be treated by the vaccine will depend on the epitope fused to the truncated σ1 protein (instant claims 6 and 7), since Kemp teaches an antigen involved in pancreatic cancer (instant claim 6) and Sanchez-Trincado teaches that identifying epitopes in antigens is an important step in designing epitope-based vaccines.
It would have been further obvious that the exact length of the truncated σ1 protein (252 or 251) or which cell line would be the more suitable for transfection of the virus vector are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize and may or may not be dependent on the reovirus strain used. Additionally,. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 2.
There would be a reasonable expectation of success because several recombinant reoviruses expressing small transgenes such as iLOV, UnaG, E4orf4, and GM-CSF have already demonstrated the feasibility of such platform and the viruses with a truncated σ1 spike all seemed potent cancer-killing viruses. The data obtained in a murine model of pancreatic cancer demonstrated a systemic increase in DC and T-cell activation (that is, inducing cell-mediated immunity) upon intratumoral administration of rS1-mmGMCSF. These data demonstrate that reoviruses expressing functional GM-CSF can be generated and have the potential to enhance anti-tumor immune responses. The GM-CSF reoviruses represent a promising new agent for use in oncolytic virotherapy strategies as taught by Kemp and discussed above.
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 1-3 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kemp (Cancer Gene Therapy (2019) 26:268–281) in view of Sanchez-Trincado (Journal of Immunology Research, Volume 2017, Article ID 2680160, 1-14), Hoeben (US 2010/0278863 A1) and Barbieri (US 2021/0300970 A1).
The teachings of Kemp and Sanchez-Tricando has been discussed above and incorporated herein.
Kemp and Sanchez-Tricando do not teach the sequences of truncated σ1 (SEQ ID NO: 1), its corresponding nucleotide sequence (SEQ ID NO: 2) and the amino acid sequences of epitopes selected from SEQ ID NO: 3 to 10. (instant claims 2,3, 8).
Hoeben teaches the reverse genetics system for viruses belonging to the Reoviridae family (i.e. Reoviruses ), various uses thereof, genetically modified Reoviruses, Reovirus selection/production and propagation systems, medicaments and vaccines (Abstract), (Both Hoeben and Kemp worked in the same laboratory lead by Diana Johanna Maria Van Den Wollenberg as shown by the authorship of Kemp’s publication and the inventorship of Hoeben’s application).
Hoeben teaches a sequence that is 100% identical to the instant SEQ ID NO: 1 (Hoeben’s SEQ ID NO: 20 see below). Please note that some of the amino acid of SEQ ID NO: 1 are represented by the letter X, wherein X is any amino acid. Hoeben also teaches a nucleotide sequence that is 99.9% identical to SEQ ID NO: 2 (Hoeben’s SEQ ID NO: 13 see below). The differences between both nucleotide sequences is due to the fact that SEQ ID NO: 1 has unidentified amino acids represented by X (which could be any amino acid) and therefore the codon sequence could also be any codon sequence, due to some variability between reoviruses variants. These differences are mostly conservative changes.
SIGMA-1 protein
Title: US-18-283-363-1
Perfect score: 1193
Sequence: 1 MDPRLREEVVRLIIALTSDN..........NLTLKTTVFDSINSRXGAXE 250
US-12-738-814-20
Sequence 20, US/12738814
Publication No. US20100278863A1
GENERAL INFORMATION
APPLICANT: Academisch Ziekenhuis Leiden Leids
APPLICANT: Hoeben, Robert C
APPLICANT: Van Den Wollenberg, Diana J M
TITLE OF INVENTION: Viral Modification
FILE REFERENCE: PC/P15477PC
CURRENT APPLICATION NUMBER: US/12/738,814
CURRENT FILING DATE: 2010-04-19
NUMBER OF SEQ ID NOS: 21
SEQ ID NO 20
LENGTH: 461
TYPE: PRT
ORGANISM: Reovirus sp.
Query Match 99.9%; Score 1192; Length 461;
Best Local Similarity 98.8%;
Matches 247; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 MDPRLREEVVRLIIALTSDNGVSLSKGLESRVSALEKTSQIHSDTILRITQGLDDANKRI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDPRLREEVVRLIIALTSDNGVSLSKGLESRVSALEKTSQIHSDTILRITQGLDDANKRI 60
Qy 61 IALEQSRDDLVASVSDAQLAISRLESSIGALQTVVNGLDSSVTQLGARVGQLETGLAELR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IALEQSRDDLVASVSDAQLAISRLESSIGALQTVVNGLDSSVTQLGARVGQLETGLAELR 120
Qy 121 VDHDNLVARVDTAERNIGSLTTELSTLTLRVTSIQADFESRISTLERTAVTSAGAPLSIR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VDHDNLVARVDTAERNIGSLTTELSTLTLRVTSIQADFESRISTLERTAVTSAGAPLSIR 180
Qy 181 NNRMTMGLNDGLXLSGNNLAIRLPGNTGLNIQNGGLQFRFNTDQFQIVNNNLTLKTTVFD 240
|||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NNRMTMGLNDGLTLSGNNLAIRLPGNTGLNIQNGGLQFRFNTDQFQIVNNNLTLKTTVFD 240
Qy 241 SINSRXGAXE 250
||||| || |
Db 241 SINSRTGAIE 250
SIGMA-1 DNA
Title: US-18-283-363-2
Perfect score: 1413.6
Sequence: 1 gctattggtcggatggatcc..........cggcactggggcatttcatc 1416
US-12-738-814-13
Sequence 13, US/12738814
Publication No. US20100278863A1
GENERAL INFORMATION
APPLICANT: Academisch Ziekenhuis Leiden Leids
APPLICANT: Hoeben, Robert C
APPLICANT: Van Den Wollenberg, Diana J M
TITLE OF INVENTION: Viral Modification
FILE REFERENCE: PC/P15477PC
CURRENT APPLICATION NUMBER: US/12/738,814
CURRENT FILING DATE: 2010-04-19
NUMBER OF SEQ ID NOS: 21
SEQ ID NO 13
LENGTH: 1416
TYPE: DNA
ORGANISM: Reovirus sp.
Query Match 99.9%; Score 1412; Length 1416;
Best Local Similarity 99.6%;
Matches 1410; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 GCTATTGGTCGGATGGATCCTCGCCTACGTGAAGAAGTAGTACGGCTGATAATCGCATTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GCTATTGGTCGGATGGATCCTCGCCTACGTGAAGAAGTAGTACGGCTGATAATCGCATTA 60
Qy 61 ACGAGTGATAATGGAGTATCACTGTCAAAAGGGCTTGAATCAAGGGTCTCGGCGCTCGAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACGAGTGATAATGGAGTATCACTGTCAAAAGGGCTTGAATCAAGGGTCTCGGCGCTCGAG 120
Qy 121 AAGACGTCTCAAATACACTCTGATACTATCCTCCGGATCACCCAGGGACTCGATGATGCA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AAGACGTCTCAAATACACTCTGATACTATCCTCCGGATCACCCAGGGACTCGATGATGCA 180
Qy 181 AACAAACGAATCATCGCTCTTGAGCAAAGTCGGGATGACTTGGTTGCATCAGTCAGTGAT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AACAAACGAATCATCGCTCTTGAGCAAAGTCGGGATGACTTGGTTGCATCAGTCAGTGAT 240
Qy 241 GCTCAACTTGCAATCTCCAGATTGGAAAGCTCTATCGGAGCCCTCCAAACAGTTGTCAAT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GCTCAACTTGCAATCTCCAGATTGGAAAGCTCTATCGGAGCCCTCCAAACAGTTGTCAAT 300
Qy 301 GGACTTGATTCGAGTGTTACCCAGTTGGGTGCTCGAGTGGGACAACTTGAGACAGGACTT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GGACTTGATTCGAGTGTTACCCAGTTGGGTGCTCGAGTGGGACAACTTGAGACAGGACTT 360
Qy 361 GCAGAGCTACGCGTTGATCACGACAATCTCGTTGCGAGAGTGGATACTGCAGAACGTAAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCAGAGCTACGCGTTGATCACGACAATCTCGTTGCGAGAGTGGATACTGCAGAACGTAAC 420
Qy 421 ATTGGATCATTGACCACTGAGCTATCAACTCTGACGTTACGAGTAACATCCATACAAGCG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 ATTGGATCATTGACCACTGAGCTATCAACTCTGACGTTACGAGTAACATCCATACAAGCG 480
Qy 481 GATTTCGAATCTAGGATATCCACATTAGAGCGCACGGCGGTCACTAGCGCGGGAGCTCCC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GATTTCGAATCTAGGATATCCACATTAGAGCGCACGGCGGTCACTAGCGCGGGAGCTCCC 540
Qy 541 CTCTCAATCCGTAATAACCGTATGACCATGGGATTAAATGATGGACTCAYGTTGTCAGGG 600
|||||||||||||||||||||||||||||||||||||||||||||||||:||||||||||
Db 541 CTCTCAATCCGTAATAACCGTATGACCATGGGATTAAATGATGGACTCACGTTGTCAGGG 600
Qy 601 AATAATCTCGCCATCCGATTGCCAGGAAATACGGGTCTGAATATTCAAAATGGTGGACTT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AATAATCTCGCCATCCGATTGCCAGGAAATACGGGTCTGAATATTCAAAATGGTGGACTT 660
Qy 661 CAGTTTCGATTTAATACTGATCAATTCCAGATAGTTAATAATAACTTGACTCTCAAGACG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 CAGTTTCGATTTAATACTGATCAATTCCAGATAGTTAATAATAACTTGACTCTCAAGACG 720
Qy 721 ACTGTGTTTGATTCTATCAACTCAAGGABAGGCGCAAYTGAGTAAAGTKMCGTGGCGTCG 780
||||||||||||||||||||||||||||:||||||||:|||| |||||::||||||||||
Db 721 ACTGTGTTTGATTCTATCAACTCAAGGACAGGCGCAATTGAGCAAAGTTACGTGGCGTCG 780
Qy 781 GCAGTGACTCCCTTGAGATTAAACAGTAGCACGAAGGTGCTGGATATGCTAATAGACAGT 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GCAGTGACTCCCTTGAGATTAAACAGTAGCACGAAGGTGCTGGATATGCTAATAGACAGT 840
Qy 841 TCAACACTTGAAATTAATTCTAGTGGACAGCTAACTGTTAGATCGACATCCCCGAATTTG 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 TCAACACTTGAAATTAATTCTAGTGGACAGCTAACTGTTAGATCGACATCCCCGAATTTG 900
Qy 901 AGGTATCCGATAGCTGATGTTAGCGGCGGTATCGGAATGAGTCCAAATTATAGGTTTAGG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 AGGTATCCGATAGCTGATGTTAGCGGCGGTATCGGAATGAGTCCAAATTATAGGTTTAGG 960
Qy 961 CAGAGCATGTGGATAGGAATTGTCTCCTATTCTGGTAGTGGGCTGAATTGGAGGGTACAG 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 CAGAGCATGTGGATAGGAATTGTCTCCTATTCTGGTAGTGGGCTGAATTGGAGGGTACAG 1020
Qy 1021 GTGAACTCCGACATTTTTATTGTAGATGATTACATACATATATGTCTTCCAGCTTTTGAC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GTGAACTCCGACATTTTTATTGTAGATGATTACATACATATATGTCTTCCAGCTTTTGAC 1080
Qy 1081 GGTTTCTCTATAGCTGACGGTGGAGATCTATCGTTGAACTTTGTTACCGGATTGTTACCA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GGTTTCTCTATAGCTGACGGTGGAGATCTATCGTTGAACTTTGTTACCGGATTGTTACCA 1140
Qy 1141 CCGTTACTTACAGGAGACACTGAGCCCGCTTTTCATAATGACGTGGTCACATATGGAGCA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 CCGTTACTTACAGGAGACACTGAGCCCGCTTTTCATAATGACGTGGTCACATATGGAGCA 1200
Qy 1201 CAGACTGTAGCTATAGGGTTGTCGTCGGGTGGTGCGCCTCAGTATATGAGTAAGAATCTG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 CAGACTGTAGCTATAGGGTTGTCGTCGGGTGGTGCGCCTCAGTATATGAGTAAGAATCTG 1260
Qy 1261 TGGGTGGAGCAGTGGCAGGATGGAGTACTTCGGTTACGTGTTGAGGGGGGTGGCTCAATT 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 TGGGTGGAGCAGTGGCAGGATGGAGTACTTCGGTTACGTGTTGAGGGGGGTGGCTCAATT 1320
Qy 1321 ACGCACTCAAACAGTAAGTGGCCTGCCATGACCGTTTCGTACCCGCGTAGTTTCACGTGA 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 ACGCACTCAAACAGTAAGTGGCCTGCCATGACCGTTTCGTACCCGCGTAGTTTCACGTGA 1380
Qy 1381 GGATCAGACCACCCCGCGGCACTGGGGCATTTCATC 1416
||||||||||||||||||||||||||||||||||||
Db 1381 GGATCAGACCACCCCGCGGCACTGGGGCATTTCATC 1416
Hoeben does not teach any of the amino acid sequences of the epitope selected from the group consisting of SEQ ID NO: 3-10 (instant claim 8)
Barbieri teaches a Covid 19 vaccine (title, entire application) based on antigenic peptides comprising the SARS-CoV-2 spike protein receptor binding domain (RBD) polypeptide or portions thereof, linked to a noncatalytic, non-toxic tetanus toxin variant and vaccine compositions comprising the same (abstract). The SARS-Co V-2 antigenic polypeptides comprise the SARS-COV-2 spike protein receptor binding domain (RBD) polypeptide [0033]. In other words, Barbieri recognizes the antigenic nature of the RBD polypeptide (instant claim 1), even when fused to another protein, and therefore fusion proteins comprising RBD can be used as vaccines for Covid-19 (instant claim 7). The fusion peptide or compositions described by Barbieri can be used to elicit an immune response that reduces COVID-19 disease progression or can reduce COVID-19 [0067]. RBD(433-524) contains the binding sites for several monoclonal antibodies (REGN10987 and REGN10933) that complementally neutralize SARS-CoV-2 infections in cultured cells [0036]. In addition, Barbieri discloses an amino acid sequence that is 100% identical to instant SEQ ID NO: 3 (instant claim 8). See below.
RBD
Title: US-18-283-363-3
Perfect score: 1054
Sequence: 1 NITNLCPFGEVFNATRFASV..........YQPYRVVVLSFELLHAPATV 194
US-17-211-379-3
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 3, US/17211379
Publication No. US20210300970A1
GENERAL INFORMATION
APPLICANT: Medical College of Wisconsin
APPLICANT: Barbieri, Joseph T
APPLICANT: Przedpelski, Amanda
APPLICANT: Pellett, Sabine
APPLICANT: Johnson, Eric A
APPLICANT: Tepp, William H
TITLE OF INVENTION: COVID-19 VACCINE
FILE REFERENCE: 650053.00784
CURRENT APPLICATION NUMBER: US/17/211,379
CURRENT FILING DATE: 2021-03-24
PRIOR APPLICATION NUMBER: US 62/994,081
PRIOR FILING DATE: 2020-03-24
PRIOR APPLICATION NUMBER: US 63/104,360
PRIOR FILING DATE: 2020-10-22
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 3
LENGTH: 196
TYPE: PRT
ORGANISM: SARS-COV-2
FEATURE:
NAME/KEY: MISC_FEATURE
LOCATION: (1)..(196)
OTHER INFORMATION: Receptor binding domain (CRBD; residues 330-521 of the spike
protein)
Query Match 100.0%; Score 1054; Length 196;
Best Local Similarity 100.0%;
Matches 194; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 NITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDL 61
Qy 61 CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYN 121
Qy 121 YLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 YLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRV 181
Qy 181 VVLSFELLHAPATV 194
||||||||||||||
Db 182 VVLSFELLHAPATV 195
It would have been obvious to one of ordinary skill in the art to combine the teachings of Kemp and Sanchez-Trincado with Hoeben and Barbieri to create a vaccine composition (as discussed above) comprising a polypeptide comprising an attenuated truncated reovirus σ1 protein (SEQ ID NO: 1, and corresponding nucleotide sequence SEQ ID NO:2 that are 100% and 99.9% identical respectively to Hoeben’s SEQ ID NO: 20 and 13) fused to an amino acid sequence of an epitope of an tumor or viral antigen (epitopes such as SARS-CoV-2 RBD as taught by Barbieri (SEQ ID NO:3)). One of ordinary skill would have been motivated to do so because Kemp teaches the truncated version of the σ1 spike (Hoeben’s SEQ ID NO: 20). And Barbieri teaches that SARS-CoV-2 RBD is a viral antigen capable of inducing an immune response including neutralizing antibodies that bind to the RBD, to treat Covid-19.
There would be a reasonable expectation of success because several recombinant reoviruses expressing small transgenes such as iLOV, UnaG, E4orf4, and GM-CSF have already demonstrated the feasibility of the platform with a fusion polypeptide comprising a truncated σ1 spike and an antigen, and RBD is a functional antigen known to be able to treat Covid-19.
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 1-6, 9-10, 13-14 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 13, 22 and 24 of copending application No. 18/258,853 (reference application.) 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 claims of 18/258,853 are drawn to the same modified reovirus as disclosed in this instant application. Therefore, the instant application claims are anticipated by the reference application claims.
Reference application claims recites a modified reovirus, comprising: a mutation in which amino acids 251 to 455 are deleted in the amino acid sequence of SEQ ID NO: 1; and one or more mutations selected from the group consisting of a mutation in which the 963rd Met in the amino acid sequence of SEQ ID NO: 2 is replaced with Val, and a mutation in which the 1265th Thr in the amino acid sequence of SEQ ID NO: 2 is replaced with Ile. SEQ ID NO: 1 is 100% identical to the instant SEQ ID NO: 1 (the truncated σ1 protein). See below for the alignment. SEQ ID NO: 2 is the Lambda-2 protein, an outer capsid protein involved in the mRNA capping of reovirus. The Lambda-2 protein is considered a viral antigen and a target for the immune system. SEQ ID NO: 3 is the reovirus outer-capsid protein Mu-1 protein (an antigen), . SEQ ID NO: 4 is the Sigma-3 protein. Therefore, reference application claims are in essence a “species” of the generic invention of instant application claims. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
SIGMA-1 PROTEIN ALIGNMENT
Title: US-18-283-363-1
Sequence: 1 MDPRLREEVVRLIIALTSDN..........NLTLKTTVFDSINSRXGAXE 250
AASEQ2_02192026_215821
Query Match 99.7%; Score 1190; DB 1; Length 250;
Best Local Similarity 100.0%;
Matches 250; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDPRLREEVVRLIIALTSDNGVSLSKGLESRVSALEKTSQIHSDTILRITQGLDDANKRI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDPRLREEVVRLIIALTSDNGVSLSKGLESRVSALEKTSQIHSDTILRITQGLDDANKRI 60
Qy 61 IALEQSRDDLVASVSDAQLAISRLESSIGALQTVVNGLDSSVTQLGARVGQLETGLAELR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IALEQSRDDLVASVSDAQLAISRLESSIGALQTVVNGLDSSVTQLGARVGQLETGLAELR 120
Qy 121 VDHDNLVARVDTAERNIGSLTTELSTLTLRVTSIQADFESRISTLERTAVTSAGAPLSIR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VDHDNLVARVDTAERNIGSLTTELSTLTLRVTSIQADFESRISTLERTAVTSAGAPLSIR 180
Qy 181 NNRMTMGLNDGLXLSGNNLAIRLPGNTGLNIQNGGLQFRFNTDQFQIVNNNLTLKTTVFD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NNRMTMGLNDGLXLSGNNLAIRLPGNTGLNIQNGGLQFRFNTDQFQIVNNNLTLKTTVFD 240
Qy 241 SINSRXGAXE 250
||||||||||
Db 241 SINSRXGAXE 250
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-7, 9, 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-34, 36-41, 43, 45, of copending application No. 18/694,516 (reference application). 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 claims of this instant application are drawn to the same modified reovirus as disclosed in 18/694,516. Therefore, the instant application claims are anticipated by reference application claims.
Reference application claims recites a recombinant vector, comprising a mutant S1 gene of reovirus and an exogenous epitope-encoding gene, wherein the mutant S1 gene has a stop codon at a 251st codon from a start codon thereof, wherein the mutant S1 gene encodes a polypeptide comprising an amino acid sequence of SEQ ID NO: 1 or 2. SEQ ID NO: 1 is 100% identical to the instant SEQ ID NO: 1 (the truncated σ1 protein). SEQ ID NO: 4 (the nucleotide sequence) is 100% identical to the instant SEQ ID NO: 2 (See below for the alignments).
SEQUENCE ALIGNMENTS
Title: US-18-283-363-1
Sequence: 1 MDPRLREEVVRLIIALTSDN..........NLTLKTTVFDSINSRXGAXE 250
AASEQ2_02202026_090947
Query Match 99.7%; Score 1190; DB 1; Length 250;
Best Local Similarity 100.0%;
Matches 250; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDPRLREEVVRLIIALTSDNGVSLSKGLESRVSALEKTSQIHSDTILRITQGLDDANKRI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDPRLREEVVRLIIALTSDNGVSLSKGLESRVSALEKTSQIHSDTILRITQGLDDANKRI 60
Qy 61 IALEQSRDDLVASVSDAQLAISRLESSIGALQTVVNGLDSSVTQLGARVGQLETGLAELR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IALEQSRDDLVASVSDAQLAISRLESSIGALQTVVNGLDSSVTQLGARVGQLETGLAELR 120
Qy 121 VDHDNLVARVDTAERNIGSLTTELSTLTLRVTSIQADFESRISTLERTAVTSAGAPLSIR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VDHDNLVARVDTAERNIGSLTTELSTLTLRVTSIQADFESRISTLERTAVTSAGAPLSIR 180
Qy 181 NNRMTMGLNDGLXLSGNNLAIRLPGNTGLNIQNGGLQFRFNTDQFQIVNNNLTLKTTVFD 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NNRMTMGLNDGLXLSGNNLAIRLPGNTGLNIQNGGLQFRFNTDQFQIVNNNLTLKTTVFD 240
Qy 241 SINSRXGAXE 250
||||||||||
Db 241 SINSRXGAXE 250
Title: US-18-283-363-2
Sequence: 1 gctattggtcggatggatcc..........cggcactggggcatttcatc 1416
US-18-694-516-4
Sequence 4, US/18694516
Publication No. US20250154204A1
SEQ ID NO 4
LENGTH: 765
TYPE: DNA
Query Match 54.0%; Score 763.4; Length 765;
Best Local Similarity 100.0%;
Matches 765; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCTATTGGTCGGATGGATCCTCGCCTACGTGAAGAAGTAGTACGGCTGATAATCGCATTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GCTATTGGTCGGATGGATCCTCGCCTACGTGAAGAAGTAGTACGGCTGATAATCGCATTA 60
Qy 61 ACGAGTGATAATGGAGTATCACTGTCAAAAGGGCTTGAATCAAGGGTCTCGGCGCTCGAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACGAGTGATAATGGAGTATCACTGTCAAAAGGGCTTGAATCAAGGGTCTCGGCGCTCGAG 120
Qy 121 AAGACGTCTCAAATACACTCTGATACTATCCTCCGGATCACCCAGGGACTCGATGATGCA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AAGACGTCTCAAATACACTCTGATACTATCCTCCGGATCACCCAGGGACTCGATGATGCA 180
Qy 181 AACAAACGAATCATCGCTCTTGAGCAAAGTCGGGATGACTTGGTTGCATCAGTCAGTGAT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AACAAACGAATCATCGCTCTTGAGCAAAGTCGGGATGACTTGGTTGCATCAGTCAGTGAT 240
Qy 241 GCTCAACTTGCAATCTCCAGATTGGAAAGCTCTATCGGAGCCCTCCAAACAGTTGTCAAT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GCTCAACTTGCAATCTCCAGATTGGAAAGCTCTATCGGAGCCCTCCAAACAGTTGTCAAT 300
Qy 301 GGACTTGATTCGAGTGTTACCCAGTTGGGTGCTCGAGTGGGACAACTTGAGACAGGACTT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GGACTTGATTCGAGTGTTACCCAGTTGGGTGCTCGAGTGGGACAACTTGAGACAGGACTT 360
Qy 361 GCAGAGCTACGCGTTGATCACGACAATCTCGTTGCGAGAGTGGATACTGCAGAACGTAAC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GCAGAGCTACGCGTTGATCACGACAATCTCGTTGCGAGAGTGGATACTGCAGAACGTAAC 420
Qy 421 ATTGGATCATTGACCACTGAGCTATCAACTCTGACGTTACGAGTAACATCCATACAAGCG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 ATTGGATCATTGACCACTGAGCTATCAACTCTGACGTTACGAGTAACATCCATACAAGCG 480
Qy 481 GATTTCGAATCTAGGATATCCACATTAGAGCGCACGGCGGTCACTAGCGCGGGAGCTCCC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GATTTCGAATCTAGGATATCCACATTAGAGCGCACGGCGGTCACTAGCGCGGGAGCTCCC 540
Qy 541 CTCTCAATCCGTAATAACCGTATGACCATGGGATTAAATGATGGACTCAYGTTGTCAGGG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 CTCTCAATCCGTAATAACCGTATGACCATGGGATTAAATGATGGACTCAYGTTGTCAGGG 600
Qy 601 AATAATCTCGCCATCCGATTGCCAGGAAATACGGGTCTGAATATTCAAAATGGTGGACTT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 AATAATCTCGCCATCCGATTGCCAGGAAATACGGGTCTGAATATTCAAAATGGTGGACTT 660
Qy 661 CAGTTTCGATTTAATACTGATCAATTCCAGATAGTTAATAATAACTTGACTCTCAAGACG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 CAGTTTCGATTTAATACTGATCAATTCCAGATAGTTAATAATAACTTGACTCTCAAGACG 720
Qy 721 ACTGTGTTTGATTCTATCAACTCAAGGABAGGCGCAAYTGAGTAA 765
|||||||||||||||||||||||||||||||||||||||||||||
Db 721 ACTGTGTTTGATTCTATCAACTCAAGGABAGGCGCAAYTGAGTAA 765
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IMMA BARRERA whose telephone number is (571) 272-0674. The examiner can normally be reached Monday - Friday 9 to 5.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/RACHEL B GILL/Primary Examiner, Art Unit 1671