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 .
Claim Status
Claims 1-10 and 14-23 are pending. Claims 11-13 and 24-56 were previously cancelled. Claims 5, 6, 9, 10, 14, 18, 21, and 22 are currently amended.
Priority
The instant application is the 371 national stage entry of PCT/IB2021/053299, filed 4/21/2021, which claims priority to the provisional application 63/013,595, filed 4/22/2020. The filing date of 4/22/2020 is acknowledged.
Information Disclosure Statement
The IDS filed on 10/23/2022 is under consideration.
Drawings
The drawings are objected to because Figures 4 and 8 are too small and grainy to compare the different types of treatment to each other. 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.
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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specifically, include SEQ ID NO: 1 and/or SEQ ID NO: 2 where relevant in the Figure legends.
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – The "Sequence Listing" has not been entered into the application because the required statement of no new matter is missing. See 37 CFR 1.825(a)(4) or 1.825(b)(5).
Required response – Applicant must provide:
A proper statement of no new matter.
Specifically, because the most recently filed CRF was submitted later than the initial filing date, Applicant is required to include a statement of no new matter within the specification on the first page.
Specification
The disclosure is objected to because of the following informalities:
Pg 20, line 29, recites “In one therapeutic approach, s” but should read as “In one therapeutic approach, a” (emphasis added).
Pg 22, line 24, recites “(SEQ ID NO: 2), or any combination thereof.the peptide (INS-HCl).” The “the peptide (INS-HCl).” portion of that sentence appears to be a typo.
Appropriate correction is required.
Claim Objections
Claim 2 is objected to because of the following informalities: Change “SARS-CoV and SARS-CoV-2” to “SARS-CoV or SARS-CoV-2” (emphasis added) in line 2 such that it is clear that the coronavirus claimed can be selected from the listed alternatives.
Appropriate correction is required.
Examiner’s Note
A rejection under 35 U.S.C. 112(a) scope of enablement was considered for claims 1-10 and 14-23, regarding whether the method could treat a corona or influenza virus infection or disease using a peptide derived from HIV-1 integrase (SEQ ID NO: 1), but not applied based on the following:
SEQ ID NO: 1 is derived from HIV-1 integrase (IN), which is required for integration of the HIV-1 genome into a host cell genome after reverse transcription has completed. Initially, there was a question of whether SEQ ID NO: 1 would similarly work to treat corona and/or influenza viruses, which, although are both RNA viruses like HIV-1, are not retroviruses and, thus, do not require an integrase/integration step.
Levin teaches that in the cytoplasm, IN catalyzes the first step of the integration through 3’-end processing in which an IN dimer removes a pGT dinucleotide from the 3’ end of each viral long terminal repeat (LTR), which is part of the preintegration complex (PIC) (US 9,738,878 B2, published 8/22/2017). After nuclear import of the PIC, the second step of the integration – strand transfer – occurs and is catalyzed by an IN tetramer; to insert the PIC into the host DNA, integrase must create a double stranded break. This process is required for HIV replication, but a limited number of integration events occur per cell (Col. 1, lines 33-55). Levin postulates that the integrase peptide SEQ ID NO: 1, which is identical to the instant SEQ ID NO: 1, works against HIV-1 infected cells by generating too many double-stranded breaks in a cell, leading to cell lysis (Col. 2, lines 58-61; Figures 7 and 8).
Loyter et al. further expands upon this concept and teaches a complex comprising the instant SEQ ID NO: 1, a linear double-stranded DNA molecule, and a targeting moiety to specifically treat cancer cells and adipocytes, through increasing numbers of double stranded DNA breaks (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018). The targeting moiety serves to target specific cell types, such as cancer and adipocytes, while the remaining complex components – the instant SEQ ID NO: 1 and double-stranded DNA molecule – work to introduce double stranded breaks into the target cell’s DNA (Pg 24, line 10 – Pg 26, line 16; also see claims 1-8).
Thus, the art indicates that this derivative of HIV-1 integrase, the instant SEQ ID NO: 1, operates through a more general mechanism involving entry into the nucleus and creation of double stranded breaks rather than a mechanism specific to the retroviral nature of HIV-1. Therefore, one would expect that this mechanism could be generally applied to a variety of cells, including those infected with corona or influenza A viruses. Thus, a 35 U.S.C.112(a) scope of enablement rejection has not been rendered here.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6-10, 14-15, 18-19, and 22-23 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.
The above claims are drawn to a method of treating a corona or influenza virus infection or disease in a subject comprising administering to the subject an effective amount of a pharmaceutical composition comprising a peptide comprising SEQ ID NO: 1 or a fragment, derivative, or analog thereof. The rejection is based on the limitation “fragment, derivative, or analog thereof” which does not disclose sufficient structure-function relationship to meet the written description requirement.
The claims indicate that SEQ ID NO: 1, or a fragment, derivative, or analog thereof, functions by treating a corona or influenza virus infection or disease. The structure-function relationship of the full-length SEQ ID NO: 1 is clear, as evidenced in the Examples of the instant specification.
The instant specification defines “fragment” as a portion of a polypeptide or nucleic acid molecule (see Pg 9, lines 9-13). This portion contains, preferably, at least 10% and up to the entire length of the reference nucleic acid or polypeptide constitutes a fragment thereof. A fragment may also contain 10-1000 nucleotides or amino acid. 10% of SEQ ID NO: 1 would result in a dipeptide (10% of 16 = 1.6, rounding up to 2 amino acids). A dipeptide randomly taken from the sequence of SEQ ID NO: 1 would read on thousands of sequences, few of which, if any, would likely retain the ability to catalyze double-stranded DNA breaks. For instance, the dipeptides KR and RK derived from the instant SEQ ID NO: 1 read on the HIV TAT sequence, which is a transcriptional activator involved in the synthesis of HIV-1 RNA and does not catalyze double-stranded DNA breaks (Charnay, N., Ivanyi-Nagy, R., Soto-Rifo, R. et al. Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein. Retrovirology 6, 74 (2009); see Pg 2, first paragraph).
The instant specification does not define a “derivative” of SEQ ID NO: 1. Merriam-Webster defines a derivative, as it pertains to chemistry, as “a chemical substance related structurally to another substance and theoretically derivable from it” or “a substance that can be made from another substance” (see Pg 1, entry #4a and b of “Derivative”, March 2016, accessed 7/22/2025 via Wayback Machine). The recitation of this limitation in claim 1, in light of this definition, substantially broadens the scope of the claim such that anything (molecule, peptide, chemical, etc.) derived from SEQ ID NO: 1 can be used in a method of treatment.
The instant specification defines "analog" as a molecule that is not identical, but has analogous functional or structural features (see Pg 7, line 27 – Pg 8, line 2). For example, a peptide analog retains the biological activity of a reference peptide, while having certain biochemical modifications that enhance the analog's function relative to the reference. Such biochemical modifications could increase the analog's protease resistance, membrane permeability, or half-life, without altering, for example, the biological function of the reference peptide. An analog may include an unnatural amino acid. The recitation of this limitation in claim 1, in light of this definition, substantially broadens the scope of the claim such that any molecule, not only amino acid sequence or peptide, can be used in the method of treatment, so long as it has analogous function or structural features to SEQ ID NO: 1.
Thus, the structural elements encompassed by “fragment, derivative, or analog thereof” substantially broadens the genus beyond the scope of the disclosure and does not indicate which structural features (i.e., a core sequence shared by all fragments, derivatives, or analogs) are necessary to maintain the disclosed function.
Loyter describes the mechanism by which SEQ ID NO: 1 interacts with many different viral and host proteins to insert the HIV-1 genome into a host cell’s genome (Pg 24, line 10 – Pg 26, line 16). SEQ ID NO: 1 binds to the HIV-1 cDNA genome and cleaves the viral DNA at each 3’ end, enters the nucleus through one of the nuclear pore complexes, binds to the host cell DNA to generate double-stranded breaks to insert the HIV-1 genome. In other words, SEQ ID NO: 1 possesses multiple roles in the insertion of the HIV-1 genome into host cells and many points of modulation. This indicates that there are a large number of different possible targets, with no expectation that a fragment for any of them will have any structural similarity to any other fragment.
Applicants have disclosed the antiviral activity of SEQ ID NO: 1, as shown in the instant Figures and Examples of the specification. SEQ ID NO: 2, which is a fragment of SEQ ID NO: 1, is also disclosed in the instant specification. Additional fragments, derivatives, or analogs of SEQ ID NO: 1 are not disclosed elsewhere in the instant application.
Consequently, it is unclear and unknown whether all fragments of the instant SEQ ID NO: 1 would retain the structural, chemical, and/or physical properties required to be able to treat corona or influenza virus infection or disease. Therefore, the instant specification does not provide adequate written description to possess the broad genus of SEQ ID NO: 1 fragments since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
Claims 1-10 and 14-23 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 method of treating a corona or influenza virus infection or disease, does not reasonably provide enablement for a method of preventing a corona or influenza virus infection or 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 use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth 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.
1. Nature of the invention: The invention is drawn to a method of treating a corona or
influenza virus infection or disease through administration of a pharmaceutical composition comprising SEQ ID NO: 1 or a fragment, derivative, or analog thereof. The definition of “treating”, as recited in the instant specification, reads on prevention in addition to treatment (see Pg 13, line 24 – Pg 14, line 3).
2. State of the prior art: Loyter, as described above, discloses that SEQ ID NO: 1 works
by overwhelming a host cell’s DNA repair machinery through introduction of so many double-stranded breaks that the cell simply dies. Loyter further teaches that in order to target a specific cell population – such as cells infected with a certain virus, such as HIV-1 – a targeting moiety is necessary to direct the integrase catalyzing the double-stranded breaks to the appropriate cell type. The targeting moiety is often an antigen or other cell-surface component expressed extracellularly on a specific cell population that distinguishes it from other cell types (Pg 24, line 10 – Pg 26, line 16; also see claims 1-8). Pre-viral infection, there would be no way to distinguish and direct the instant SEQ ID NO: 1 to the relevant infected cells as there would be no way to distinguish these cells from unaffected ones.
Levin postulates that the lack of a targeting moiety is not an issue with an active infection, such as HIV-1, because infected cells are already undergoing DNA doubles-stranded breaks as part of the HIV-1 lifecycle, and, therefore, these cells are already primed to be impacted by SEQ ID NO: 1 (Col. 2, lines 58-61; Figures 7 and 8). This idea further suggests that SEQ ID NO: 1 could not prevent a corona or influenza virus infection.
3. The relative skill of those in the art: The relative skill of those in the art is high.
4. The predictability or unpredictability of the art: One would have predicted that
administration of the given SEQ ID NO: 1 or a fragment, derivative, or analog thereof would not effectively prevent corona or influenza virus infections or diseases based upon the known mechanism of action. The prior art, as described above, recognized that SEQ ID NO: 1 exerted its therapeutic effects through the creation of an overwhelming amount of double-stranded DNA breaks. In both of the situations described by Loyter and Levin above – i.e., using a targeting moiety to attack specific cell types or relying on an active infection to make certain cell types more susceptible – neither would be able to prevent a corona or influenza virus infection or disease. In healthy, non-infected individuals, there would be no means to distinguish cells that might potentially be impacted by a corona or influenza virus from healthy cells by using a targeting moiety. Further, healthy cells would not be as susceptible to double-stranded DNA breaks as cells experiencing an active HIV-1 infection.
5. The breadth of the claims: The claims are drawn to both the treatment and prevention
of a corona or influenza virus infection or diseases through administration of a pharmaceutical compound comprising the instant SEQ ID NO: 1 or fragments, derivatives, or analogs thereof.
6. The amount of direction or guidance presented: Neither Loyter nor Levin disclose
starting points from which a method of prevention of a corona or influenza virus infection or disease could be extrapolated.
7. The presence or absence of working examples: The instant specification discloses
treatment of individuals diagnosed with COVID-19 and/or exhibiting active symptoms of COVID-19. None of the examples provided demonstrate prevention wherein the instant SEQ ID NO: 1 is provided to individuals prior to their need for treatment or upon infection by a corona or influenza virus.
8. The quantity of experimentation necessary: As there are no working examples,
reasonable guidance with respect to preventing a corona or influenza virus infection or disease in a subject did not exist at the time of filing. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively prevent a corona or influenza virus infection or disease.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the claimed invention for a method of prevention of corona or influenza virus infection or disease through administration of a pharmaceutical composition comprising the instant SEQ ID NO: 1.
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 6-9 and 16-17 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.
Claim 6 recites “a poloxomer having the structure of Formula I, wherein… a is an integer from 50 to 12, and b is an integer from 15-40.” Claims 7-9, 16, and 17 recite similar variations of this limitation, wherein a and b are further limited. Even with the values of a and b specified, it is unclear whether only one type of chain in a poloxamer mixture must meet the length limitations described by a and b or whether a and b represent average values of a polydisperse mixture. This renders the scope of the claims indefinite.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims 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, 2, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Loyter et al. (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018) in view of Xiao (WO 2014139468 A1, published 9/18/2014).
Loyter teaches compositions and methods for inducing DNA breaks in specifically-targeted cells, in particular cancer and HIV-infected cells, thereby promoting cell death (Abstract). Specifically, Loyter teaches a method for treating a disease or condition in a subject in need of such treatment, comprising the steps of targeting a specific cell populations of the subject with a complex comprising an integrating enzyme, such as SEQ ID NO: 1 (which is identical to the instant SEQ ID NO: 1), a linear double-stranded DNA molecule that the integrating enzyme can recognize, and a targeting moiety (claims 36-40). As described above, the targeting moiety serves to target specific cell types while the remaining complex components – the instant SEQ ID NO: 1 and double-stranded DNA molecule – introduce double stranded breaks into the target cell’s DNA (Pg 24, line 10 – Pg 26, line 16; also see claims 1-8). The specific population of cells to be destroyed is selected from the group consisting of: cancer cells, virally-infected cells, lipocytes, yeast cells and bacteria cells and the disease or condition is selected from the group consisting of cancer, viral-infection, obesity, yeast infection and bacterial infection (Pg 10, lines 13-16).
Loyter does not teach that the method can be used to treat a corona or influenza virus infection or disease.
Xiao teaches compositions of fusion molecules comprising a cytokine moiety and a targeting moiety as well as methods of treatment. The targeting moiety comprises one or more ligands that are each a peptide, protein, or a small molecule that recognizes a receptor on the target, such as but not limited to cells or viral particles. The targeting moiety targets the fusion molecules to the site of the targets and the cytokine moiety exerts its function at the site of the target, thereby resulting in enhanced activity of the cytokine (Abstract).
In one embodiment, the targets are virus-infected cells or virus particles. The targeting moiety of the fusion protein comprises at least a fragment or variation of a ligand of a receptor expressed on, or attached to the surface of the cells that virus are to infected, such as but not limited to, receptors expressed on hepatocytes before or after infection by a hepatitis virus (HAV, or HBV, or HCV). In another embodiments, the targeting moiety comprises at least a fragment or a variation of a surface antigen or coat protein of viral particles, such as but not limited to hemagglutinin of human influenza virus or peplomer protein E2 of SARS-coronavirus, or the spike protein of SARS-coronavirus, or hemagglutinin-esterase glycoprotein of SARS-coronavirus (Pg 8, final paragraph – Pg 9, first paragraph).
Regarding claims 1 and 2, Loyter teaches a method of treating a disease or condition by selectively destroying certain cell populations comprising administering to a subject a complex comprising the instant SEQ ID NO: 1. Xiao teaches fusion proteins designed to specifically target virus-infected cells or virus particles themselves, specifically human influenza virus or SARS-coronavirus (SARS-CoV). Therefore, it would be prima facie obvious to use the influenza and/or SARS-CoV targeting moieties, taught by Xiao, in a method of treating a disease or condition by targeting certain cell populations for destruction, as taught by Loyter, in order to create a method of treating corona or influenza virus infection or disease. One skilled in the art would have a reasonable expectation of success as Xiao had already established targeting moieties that could be used to direct machinery to influenza and coronavirus-infected cells and Loyter had demonstrated that SEQ ID NO: 1 could effectively treat other virus-infected cells.
Regarding claims 18 and 19, Xiao teaches the composition can be delivered by any suitable route such as infusion intravenously, intraperitoneally, subcutaneously, intramuscularly, by reservoir/pumping devices, by skin patches, or by inhalation (Pg 11, third paragraph under “Methods of using the compositions”).
Claims 1-3 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Loyter et al. (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018) and Xiao (WO 2014139468 A1, published 9/18/2014), as applied to claims 1, 2, and 18-19 above, and further in view of Coronaviridae Study Group (“CSG”, Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 5, 536–544 (2020)).
The teachings of Loyter and Xiao have been set forth above. Loyter and Xiao do not teach a method of treating a corona or influenza virus infection or disease wherein the disease is COVID-19.
CSG teaches that the respiratory disease COVID-19 is caused by SARS-CoV-2 (Abstract). SARS-CoV-2 is closely related to MERS-CoV and SARS-CoV based on phylogeny, which influences the naming conventions (Box 1).
Regarding claim 3, Loyter and Xiao teach a method of treating a corona or influenza virus infection or disease, including MERS-CoV, comprising administering to a subject a pharmaceutical composition comprising the instant SEQ ID NO: 1. CSG teaches that the disease COVID-19 is caused by SARS-CoV-2, which is closely related to MERS-CoV and SARS-CoV based on phylogeny. Therefore, it would be prima facie obvious to apply the method of treating a coronavirus infection or disease comprising administering a pharmaceutical composition comprising the instant SEQ ID NO: 1, as taught by Loyter and Xiao, to a method of treating COVID-19 disease, taught by CSG, in order to treat additional species of coronavirus. One skilled in the art would have a reasonable expectation of success as CSG established that MERS-CoV and SARS-CoV-2, which causes COVID-19, are closely related.
Claims 1, 2, 4, 5 and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Loyter et al. (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018) and Xiao (WO 2014139468 A1, published 9/18/2014), as applied to claims 1, 2, and 18-19 above, and further in view of Steckbeck (CA 3055248 A, published 9/7/2018).
The teachings of Loyter and Xiao have been set forth above. Loyter and Xiao do not teach a method wherein the influenza virus in influenza A.
Steckbeck teaches peptides that can comprise antimicrobial, antiviral, antifungal, or antitumor activity when administered to a subject (Abstract). Steckbeck claims a method of treating a viral infection comprising administering to a primate a therapeutic peptide, salt, or composition thereof (Claim 86). Steckbeck also claims a method of treating enveloped viruses such as coronavirus or orthomyxovirus among others (claim 90). The instant specification discloses that the Orthomyxoviridae family of viruses includes influenza A (Pg 9, lines 16-25).
Regarding claim 4, Loyter and Xiao teach a method of treating a corona or influenza virus infection or disease comprising administering to a subject a pharmaceutical composition comprising the instant SEQ ID NO: 1. Steckbeck teaches peptides, their salts, and compositions thereof used in methods of treating primate subjects with viral infections such as influenza A. Therefore, it would be prima facie obvious to use the method taught by Loyter and Xiao to treat influenza A. One skilled in the art would have a reasonable expectation of success because influenza A is an influenza virus species and Steckbeck had already established that influenza A could be effectively treated with other types of peptide therapeutics.
Regarding claim 5, Steckbeck teaches that a peptide salt of the invention can include a halide salt (e.g. chloride) ([0082-0083]). Steckbeck further teaches that an aerosol can be employed to administer a peptide or salt thereof to a respiratory tract and take the form of a dry powder or an aqueous solution. Aerosol pharmaceutical formulations may comprise, for example, a physiologically acceptable buffered saline solution containing between about 0.001mg/ml and about 100mg/ml of one or more peptides specific for an indication or disease to be treated ([0179]).
The MPEP 2144.05 states that "[i]n the case where the claimed ranges 'overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists" quoting In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). In the instant case, the concentrations taught overlap on the instantly claimed dosages.
Regarding claims 20 and 21, Steckbeck teaches that the peptide, salt thereof, or pharmaceutical composition comprising a peptide or salt thereof can be administered at a dose from about 1mg to about 1000mg ([0187]).
Xiao further teaches that the composition can be administered once a day or less frequently (Pg 11, final paragraph, first line).
Regarding claims 22 and 23, Steckbeck further claims the method further comprises administering an antibiotic or an additional antiviral compound, such as Acyclovir, Brivudine, Docosanol, Famciclovir, Idoxuridine, Penciclovir, Trifluridine, Valacyclovir, Amantadine, Rimantadine, a neuraminidase inhibitor, Oseltamivir, Zanamivir, a salt of any of these, and any combination thereof (claims 92 and 94).
Claims 1, 2, 4-10, 14, and 16-23 are rejected under 35 U.S.C. 103 as being unpatentable over Loyter et al. (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018), Xiao (WO 2014139468 A1, published 9/18/2014), and Steckbeck (CA 3055248 A, published 9/7/2018), as applied to claims 1, 2, 4, 5, and 18-23 above, and further in view of Gopinath et al. (WO 2011060922 A1, published 5/26/2011).
The teachings of Loyter, Xiao, and Steckbeck have been set forth above. Loyter, Xiao, and Steckbeck do not teach the addition of poloxamer having the structure of Formula I to the pharmaceutical composition nor the pH of the composition.
Gopinath teaches pharmaceutical compositions and formulations of growth hormone (GH) and insulin-like growth factor (IGF-1) combination compositions which provide stable pharmaceutical compositions without aggregation formation at a desirable pH, and to processes of preparation thereof (Abstract).
Gopinath teaches that in pharmaceutical formulations, the dosage of therapeutic protein is important and must be kept within controlled ranges over an extended period of time. The use of solubilizing agents is often required to obtain and maintain the right concentration of protein in solution and particularly to solubilize high amounts of proteins (Pg 2, lines 17-20).
Further, the composition is comprised of a “buffer”, which denotes a pharmaceutically acceptable buffer which preferably confers a pH of 5-6.5 (Pg 4, lines 15-16). The pH can be adjusted from about 5 to 7 to preferably about 5.8 to 6.2 (Pg 10, lines 21-22).
Gopinath further teaches the addition of surfactant to the composition. Surfactants disclosed in the present invention can be selected from the list: polysorbate (Tween) or a poloxamer such as polysorbate 80, polysorbate 20 or poloxamer 188. Preferably the surfactant is non-ionic, more preferably is a polysorbate (Tween) such as polysorbate 80, polysorbate 20 or a poloxamer such as poloxamer 188, more preferably polysorbate 20 or poloxamer 188 in a concentration range from about 0.01 to 3 % (w/w) preferably from about 0.03 to 0.50 % (w/w) and more preferably of about 0.2% (w/w) (Pg 11, lines 5-11). The instant specification states that in poloxamer 188, a=80 and b=27 (Pg 23, line 17).
Regarding claim 6-9, Loyter and Xiao teach a method of treating a corona or influenza virus infection or disease comprising administering to a subject an effective amount of a pharmaceutical composition comprising the instant SEQ ID NO: 1. Gopinath teaches pharmaceutical compositions designed for increased stability, which includes maintaining pH between 5-7 and adding surfactant such as poloxamer 188. It would be prima facie obvious to formulate the pharmaceutical composition, taught by Gopinath, in a method of treating corona or influenza virus infection or disease, as taught by Loyter and Xiao, in order to increase the stability of SEQ ID NO: 1 over time. One skilled in the art would have a reasonable expectation of success because such a formulation had been used prior to improve similar protein- or peptide-based pharmaceutical compositions.
The MPEP 2144.05 states that "[i]n the case where the claimed ranges 'overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists" quoting In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). In the instant case, the concentrations taught overlap on the instantly claimed dosages.
Regarding claims 10 and 14, Gopinath also teaches that, optionally, the composition may also comprise bulking agents such as trehalose, mannitol, sorbitol or sucrose between 1 to 10 % (w/w) of mannitol, sorbitol, trehalose or sucrose (Pg 11, last line – Pg 12, line 3).
Regarding claims 16 and 17, Gopinath teaches the addition of surfactants such as poloxamer 188 in the range of 0.01 to 3 % (w/w), preferably from about 0.03 to 0.50 % (w/w), and more preferably of about 0.2% (w/w) (Pg 11, lines 5-11; Pg 23, lines 12-30), as well as bulking agents such as mannitol in the range of 1-10% (w/w) (Pg 11, last line – Pg 12, line 3). Loyter, Xiao, and Steckbeck teach that the instant SEQ ID NO: 1 can administered in a range of about 0.001mg/ml and about 100mg/ml.
Claims 1, 2, 4-10, and 14-23 are rejected under 35 U.S.C. 103 as being unpatentable over Loyter et al. (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018), Xiao (WO 2014139468 A1, published 9/18/2014), Steckbeck (CA 3055248 A, published 9/7/2018), and Gopinath et al. (WO 2011060922 A1, published 5/26/2011), as applied to claims 1, 2, 4-10, 14, and 16-23 above, and further in view of “D-Mannitol” (Chem-Impex, 2014).
The teachings of Loyter, Xiao, Steckbeck, and Gopinath have been set forth above. Loyter, Xiao, Steckbeck, and Gopinath do not teach the addition of D-mannitol to the pharmaceutical composition.
D-mannitol is employed in the formulation of intravenous solutions, enhancing the stability and solubility of active ingredients (Pg 3).
Regarding claim 15, Loyter, Xiao, Steckbeck, and Gopinath teach a method of treating corona or influenza virus infection or disease comprising administering a composition comprising the instant SEQ ID NO: 1 of various formulations, including some formulations with mannitol. The D isomer of mannitol is useful in that it increase the stability of the formulation and increases the solubility of the active ingredients. It would be therefore prima facie obvious to use D-mannitol in the pharmaceutical composition comprising the instant SEQ ID NO: 1 in a method of treating corona or influenza virus infection or diseases. One skilled in the art would have a reasonable expectation of success because D-mannitol is known to improved pharmaceutical formulations and compositions for the reasons described above.
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, 5-10, 14, and 16-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 12, 14, and 51 of copending Application No. 17/270,262 (‘262 reference application, claim set filed 12/26/2024) in view of Loyter et al. (WO 2018/215999 A1, filed 10/25/2017, published 11/29/2018) and Xiao (WO 2014139468 A1, published 9/18/2014). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 of copending Application No. ‘262 recites a pharmaceutical composition comprising from 1 to 5 mg/ml of a hydrochloride salt of a peptide comprising amino acid sequence SEQ ID NO: 1; from 0.5 wt% to 5 wt% of a poloxamer having the structure of Formula I:
PNG
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140
400
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a saccharide selected from a disaccharide and a polysaccharide, the pharmaceutical composition comprising from about 1 wt% and about 20 wt% of the saccharide; and a pharmaceutically acceptable carrier, wherein the pH of the composition is between 4.5 and 6.5, and wherein a is 80, and b is 27, wherein when the pharmaceutical composition is diluted 10-fold in phosphate buffered saline to prepare a solution, the solution is clear. SEQ ID NO:1 of copending Application No. ‘262 and the instant SEQ ID NO: 1 are identical.
Dependent claims further specify different formulations of the composition (claims 8, 14, and 51) and the disaccharide species (claim 12).
Copending Application No. ‘262 does not claim a method of treating a corona or influenza virus infection or disease.
As described above, Loyter teaches compositions and methods for inducing DNA breaks in specifically-targeted cells, in particular cancer and HIV-infected cells, thereby promoting cell death; the invention relies on a complex comprising SEQ ID NO: 1, a linear double-stranded DNA molecule, and a targeting moiety to bring the complex to an appropriate cell type. Xiao teaches compositions of fusion molecules comprising a cytokine moiety and a targeting moiety as well as methods of treatment and, in particular, targeting moieties for corona or influenza virus infected cells.
It would have been prima facie obvious to one of ordinary skill in the art to incorporate the teachings of copending Application No. ‘262 into the method taught by Loyter and Xiao thereby arriving at the instant invention. One would have been motivated to do so in order to treat more viruses in addition to HIV-1 with SEQ ID NO: 1. Thus, the above claims are rendered obvious in light of the teachings of copending Application No. ‘262.
Conclusion
No claim is allowed.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658