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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 10/16/2023 before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-8 and 13-25 are pending. Claims 1-8 and 13-25 are under examination.
Claim Objections
Claim 5 is objected to because of the following informalities. Claim 5 uses the phrase “a peptide having an amino acid sequence identified as…”. Less cumbersome language would be “a peptide having the amino acid sequence SEQ ID NO:…”. Appropriate correction is required.
Claim 18 is objected to because of the following informalities. Claim 18 uses the phrase “the peptide identified as…”. It would be more consistent to write “the peptide having the amino acid sequence SEQ ID NO:…”. Appropriate correction is required.
Claim 19 is objected to because of the following informalities. Claim 19 uses the phrase “peptide possessing” whereas all other such claims use “peptide having”. Please update this for consistency. Appropriate correction is required.
Claim 22 is objected to because of the following informalities. Claim 22 uses the phrase “the peptide identified as…”. It would be more consistent to write “the peptide having the amino acid sequence SEQ ID NO:…”. Appropriate correction is required.
Claim Interpretation
To advance compact prosecution, claims 7, 14, and 24 have been interpreted to reference the listed virus families in the alternative.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7, 14, and 24 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.
Regarding claim 7, this claim recites the phrase “caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families”. This implies that the referenced virus belongs to all of the listed families which is not possible.
The specification provides some guidance: “In particular, the invention relates to the inhibition of viral infection originated by viruses that directly infect the epithelial cells of the respiratory system, such as the viruses of the Coronaviridae. Ortho- and Para-myxoviridae. Picornaviridae and Adenoviridae families.” (Specification, page 5, line 5).
However, the specification also uses the same language as claim 7 here: “In a particular embodiment of the method of the invention, the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.” (Specification, page 8, line 11).
Applicant almost certainly means for these families to be listed in the alternative. However, the phrase “…originated by viruses that directly infect the epithelial cells…” recites “viruses” in the plural which is compatible with listing the families with “and” in the conjunctive. When this language is invoked with “virus” in the singular, the present indefiniteness is created.
The specification does recites these families listed in the alternative: “In a preferred embodiment of the invention method, the infection is caused by a virus that is selected from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus and classical swine fever virus.” (Specification, page 8, line 13).
Clarification is required.
Regarding claim 14, this claim recites the phrase “caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families”. All of the issues described above with respect to claim 7 apply to claim 14. Clarification is required.
Regarding claim 24, this claim recites the phrase “caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families”. All of the issues described above with respect to claim 7 apply to claim 24. Clarification is required.
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 5-8, 13-18, and 21-25 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 treating coronavirus, influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, and classical swine fever virus, does not reasonably provide enablement for all the listed peptides to treat and prevent any virus that infects epithelial cells of the mammalian respiratory system, the entirety of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families, nor cytomegalovirus. The specification also does not provide enablement for the prevention of any virus. 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.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
The breadth of the claims;
The phrase “viruses that infect the epithelial cells of the mammalian respiratory system” is extremely broad. The claimed families are also very broad, given the size of virus families.
The nature of the invention;
The invention is a group of peptides and method of using said peptides to treat infections caused by viruses that infect the epithelial cells of the mammalian respiratory system.
The state of the prior art;
Viruses have tremendous variety in structure and function. Louten (Louten, Jennifer. Essential human virology : 19 (2016)) discloses that: “The classification of viruses is useful for many reasons. It allows scientists to contrast viruses and to reveal information on newly discovered viruses by comparing them to similar viruses. It also allows scientists to study the origin of viruses and how they have evolved over time. The classification of viruses is not simple, however—there are currently over 2800 different viral species with very different properties!” (Louten, page 26, col. 1, para .1). This variety manifests itself within each family of viruses. Taking orthomyxoviruses as an example, Abdelwhab et al. (Abdelwhab, et al.. Recent advances in animal virology. Singapore: Springer Singapore, 351-378 (2019) discloses that: “Viruses are highly evolving, and the genetic reassortment among viruses is seen only within the same genus and never been reported in between viruses from different genera. Influenza A viruses (IAVs) infect humans and different animals including birds, pigs, equines, dogs, cats, whales and seals. To date, there are 18 different haemagglutinins (H1 to H18) and 11 different neuraminidases (N1 to N9) for influenza A viruses.” (Abdelwhab et al., page 351, Abstract). Abdelwhab also discloses several genera of viruses within this family in Table 19.1 (Abdelwhab, page 355, Table 19.1)Using cytomegalovirus as an example, the mechanism of virus drug resistance are complex. Strasfeld et al. (Strasfeld, Lynne, and Sunwen Chou. "Antiviral drug resistance: mechanisms and clinical implications." Infectious disease clinics of North America 24.2: 413. (2010)) discloses that: “The literature on CMV drug resistance mutations is extensive [92–99], especially for ganciclovir. Over 90% of resistant CMV isolates obtained following ganciclovir exposure contain one or more characteristic mutations in the viral UL97 kinase gene [98], which apparently decrease the phosphorylation of ganciclovir without impairing the important functions of this kinase in viral replication [98,100,101]. Unlike the case with HSV TK mutations, CMV UL97 drug-resistance mutations cluster tightly at codons 460, 520, and 590–607 (Figure 1). Mutations M460V/I, H520Q, C592G, A594V, L595S, and C603W are among the most frequently encountered in ganciclovir-resistant isolates [98]. These mutations individually confer moderate ganciclovir resistance, with an IC50 ratio of 5 to 10, except for C592G which confers low-level ganciclovir resistance, with an IC50 ratio of about 2.5 [98].
These IC50 ratios are based on recombinant phenotyping data [99], which are also available for many other less common UL97 mutations. The accumulated genotype-phenotype correlations are the basis for the CMV genotypic resistance testing that is available in various commercial and academic laboratories.” (Strasfeld et al., page 6, para. 2).
The level of one of ordinary skill;
A person of ordinary skill in the art typically would possess at least a Master’s level education and frequently a Ph.D.
The level of predictability in the art;
The predictability regarding how changes in viral sequence can affect the properties of the mature virus is low due to the unpredictability of amino acid substitutions. Regarding these substitutions, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
(F) The amount of direction provided by the inventor and the existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
A tremendous amount of experimentation would be required to test the efficacy of the claimed peptides against all the claimed viral targets. Even a viral family, as described above, is a large and complex set of viruses.
Regarding claim 5, this claim uses the phrase “viruses that infect epithelial cells of the mammalian respiratory system”. As described above, this covers a very large number of viruses in different families. Even within the same family, different genera exist with different properties. Applicant provides data for peptide efficacy against eight viruses, and determining efficacy against the breadth of viruses claimed would require undue experimentation.
Regarding the issue of prevention, prevention data is only shown against SARS-CoV-2. Furthermore, the data shown in Table 8 of the specification only shows a reduced likelihood of contracting SARS-CoV2, not the ability prevent SARS-CoV-2 in an absolute sense as is required by the term “prevention”. The experimentation to determine that status of prevention efficacy for each peptide against each virus would be at least as laborious as determining treatment and therefore would also require undue experimentation.
Consequently, claim 5 is rejected.
Regarding claim 6, this claim has the same scope as claim 5 and therefore also would require undue experimentation. Consequently, claim 6 is rejected.
Regarding claim 7, this claim recites treatment of a family of viruses. As described above, virus families have different genera with different properties. Consequently, a smaller, but still large number of viruses would have to be tested and therefore would require undue experimentation. Claim 7 is rejected
Regarding claim 8, claim 8 recites cytomegalovirus. As noted above, cytomegalovirus possess complex resistance mechanisms. With no data of efficacy, experiments would have to be setup for the claimed peptides. The complexity of acquiring data in human subjects would require undue experimentation. Claim 8 is rejected
Regarding claim 13, this claim uses the phrase “viruses that infect epithelial cells of the mammalian respiratory system”. As described above, this covers a very large number of viruses in different families. Even within the same family, different genera exist with different properties. Applicant provides data for peptide efficacy against eight viruses, and determining efficacy against the breadth of viruses claimed would require undue experimentation.
Regarding the issue of prevention, prevention data is only shown against SARS-CoV-2. Furthermore, the data shown in Table 8 of the specification only shows a reduced likelihood of contracting SARS-CoV2, not the ability prevent SARS-CoV-2 in an absolute sense as is required by the term “prevention”. The experimentation to determine that status of prevention efficacy for each peptide against each virus would be at least as laborious as determining treatment and therefore would also require undue experimentation.
Consequently, claim 13 is rejected.
Regarding claim 14, this claim recites treatment of a family of viruses. As described above, virus families have different genera with different properties. Consequently, a smaller, but still large number of viruses would have to be tested and therefore would require undue experimentation. Claim 14 is rejected.
Regarding claim 15, claim 15 recites cytomegalovirus. As noted above, cytomegalovirus possess complex resistance mechanisms. With no data of efficacy, experiments would have to be setup for the claimed peptides. The complexity of acquiring data in human subjects would require undue experimentation. Claim 15 is rejected
Regarding claim 16, this claim has the same scope as claim 13 and therefore also would require undue experimentation. Consequently, claim 16 is rejected.
Regarding claim 17, this claim has the same scope as claim 13 and therefore also would require undue experimentation. Consequently, claim 17 is rejected.
Regarding claim 18, this claim has the same scope as claim 13 and therefore also would require undue experimentation. Consequently, claim 18 is rejected.
Regarding claim 21, this claim uses the phrase “viruses that infect epithelial cells of the mammalian respiratory system”. As described above, this covers a very large number of viruses in different families. Even within the same family, different genera exist with different properties. Applicant provides data for peptide efficacy against eight viruses, and determining efficacy against the breadth of viruses claimed would require undue experimentation.
Regarding the issue of prevention, prevention data is only shown against SARS-CoV-2. Furthermore, the data shown in Table 8 of the specification only shows a reduced likelihood of contracting SARS-CoV2, not the ability prevent SARS-CoV-2 in an absolute sense as is required by the term “prevention”. The experimentation to determine that status of prevention efficacy for each peptide against each virus would be at least as laborious as determining treatment and therefore would also require undue experimentation.
Consequently, claim 21 is rejected.
Regarding claim 22, this claim has the same scope as claim 21 and therefore also would require undue experimentation. Consequently, claim 22 is rejected.
Regarding claim 23, this claim has the same scope as claim 21 and therefore also would require undue experimentation. Consequently, claim 23 is rejected.
Regarding claim 24, this claim recites treatment of a family of viruses. As described above, virus families have different genera with different properties. Consequently, a smaller, but still large number of viruses would have to be tested and therefore would require undue experimentation. Claim 24 is rejected.
Regarding claim 25, claim 25 recites cytomegalovirus. As noted above, cytomegalovirus possess complex resistance mechanisms. With no data of efficacy, experiments would have to be setup for the claimed peptides. The complexity of acquiring data in human subjects would require undue experimentation. Claim 25 is rejected.
Claims 7, 14, and 24 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 caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae or adenoviridae families, does not reasonably provide enablement for caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families. 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.
All of the Wands factors listed above are also relevant to this rejection, but prior art is not the focus of this rejection.
Regarding claim 7, this claim recites the phrase “caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families”. This implies that the referenced virus belongs to all of the listed families which is not possible. Because the target virus cannot simultaneously be a member of several families at once, this virus cannot be treated because the virus cannot be defined. Claim 7 is rejected.
Regarding claim 14, this claim recites the phrase “caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families”. This implies that the referenced virus belongs to all of the listed families which is not possible. Because the target virus cannot simultaneously be a member of several families at once, this virus cannot be treated because the virus cannot be defined. Claim 14 is rejected.
Regarding claim 24, this claim recites the phrase “caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families”. This implies that the referenced virus belongs to all of the listed families which is not possible. Because the target virus cannot simultaneously be a member of several families at once, this virus cannot be treated because the virus cannot be defined. Claim 24 is rejected.
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.
Claims 1 and 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ortega et al. , US 9,205,128, published 12/8/2015.
Regarding claim 1, claim 1 recites a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Consequently, claim 1 is anticipated by Ortega et al. and rejected.
Regarding claim 2, claim 2 recites a pharmaceutical composition comprising at least one peptide having an amino sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20 and a pharmaceutically acceptable excipient.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al. 2, col. 4, line 43).
Consequently, claim 2 is anticipated by Ortega et al. and rejected.
Claims 1 and 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ortega et al. , US 9,205,128, published 12/8/2015.
Regarding claim 1, claim 1 recites a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Consequently, claim 1 is anticipated by Ortega et al. and rejected.
Regarding claim 2, claim 2 recites a pharmaceutical composition comprising at least one peptide having an amino sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20 and a pharmaceutically acceptable excipient.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al. 2, col. 4, line 43).
Consequently, claim 2 is anticipated by Ortega et al. and rejected.
Claim 4 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ortega et al. , US 9,205,128, published 12/8/2015 .
Regarding claim 4, claim 2 is anticipated as described above. Claim 4 further recites the case wherein the composition is formulated for administration by the parenteral or mucosal route. Ortega discloses: “Administration routes include the parenteral route and those by which the agent is delivered through the mucosae of the subject.” (Ortega et al., col. 14, line 20). Consequently, claim 4 is anticipated by Ortega et al. and rejected.
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.
Claims 3, 19, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al. , US 9,205,128, published 12/8/2015.
Regarding claim 3, claim 2 is anticipated as described above. Claim 3 recites the case wherein the pharmaceutical composition additionally comprises a peptide having the sequence SEQ ID NO: 1.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical composition of Ortega with SEQ ID NO: 1 disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 3 is obvious over Ortega et al. and rejected.
Regarding claim 19, claim 19 recites: “A pharmaceutical combination comprising two or more peptides possessing an amino acid sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.”
Applicant SEQ ID NOs: 1, 14, and 15 are anticipated by Ortega:
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al., col. 4, line 43).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine peptides disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 19 is obvious over Ortega et al. and rejected.
Regarding claim 20, claim 19 is obvious as described above. Claim 20 further recites the case wherein the peptides are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the peptides of Ortega in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptides of Ortega, it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide 1 and peptide 2 together are simultaneous, peptide 1 followed by peptide 2 is sequential, and peptide 2 followed by peptide 1 is also sequential. Consequently, claim 20 is obvious over Ortega et al. and rejected.
Claims 1-4, 19, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al. , US 9,205,128, published 12/8/2015, in view of Eldeeb et al. (Eldeeb, Mohamed A., et al. BioEssays 41.11: 1800167 (2019)) and Mischerikow, et al. (Mischerikow, et al. Proteomics 11.4: 571-589 (2011)).
Regarding claim 1, claim 1 recites a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 2:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega et al. does not disclose acetylation at position 1.
However, Eldeeb discloses that N-terminal acetylation stabilizes peptides: “This is exemplified by the observation that indeed Nt-acetylated protein fragments exhibit higher metabolic stability profiles in vivo than non-acetylated counterparts.” (Eldeeb et al., page 5, col. 1, para. 2)
Also, Mischerikow discloses that N-terminal acetylation is extremely common in eukaryotic proteins and peptides: “N-terminal acetylation is one of the most common and abundant protein modifications in eukaryotes, estimated to occur in about 85% of mammalian proteins and 60% of yeast proteins, occurring significantly less frequent in prokaryotes.” (Mischerikow et al., page 572, col. 1, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply N-terminal acetylation to the peptide of Ortega to arrive at the claimed invention. A person of ordinary skill in the would have a reasonable expectation of success due to the frequency of mammalian acetylation disclosed by Mischerikow and would be motivated to achieve the increased stability as described by Eldeeb. Consequently, claim 1 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 2, claim 2 recites a pharmaceutical composition comprising at least one peptide having an amino sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20 and a pharmaceutically acceptable excipient.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 2:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega et al. 2 does not disclose acetylation at position 1.
However, Eldeeb discloses that N-terminal acetylation stabilizes peptides: “This is exemplified by the observation that indeed Nt-acetylated protein fragments exhibit higher metabolic stability profiles in vivo than non-acetylated counterparts.” (Eldeeb et al., page 5, col. 1, para. 2)
Also, Mischerikow discloses that N-terminal acetylation is extremely common in eukaryotic proteins and peptides: “N-terminal acetylation is one of the most common and abundant protein modifications in eukaryotes, estimated to occur in about 85% of mammalian proteins and 60% of yeast proteins, occurring significantly less frequent in prokaryotes.” (Mischerikow et al., page 572, col. 1, para. 3).
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al., col. 4, line 43).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply N-terminal acetylation to the peptide and pharmaceutically acceptable excipient of Ortega to arrive at the claimed invention. A person of ordinary skill in the would have a reasonable expectation of success due to the frequency of mammalian acetylation disclosed by Mischerikow and would be motivated to achieve the increased stability as described by Eldeeb. Consequently, claim 2 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 3, claim 2 is obvious as described above. Claim 3 recites the case wherein the pharmaceutical composition additionally comprises a peptide having the sequence SEQ ID NO: 1.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical composition of Ortega, Eldeeb, and Mischerikow with SEQ ID NO: 1 disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 3 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 4, claim 2 is obvious as described above. Claim 4 further recites the case wherein the composition is formulated for administration by the parenteral or mucosal route. Ortega discloses: “Administration routes include the parenteral route and those by which the agent is delivered through the mucosae of the subject.” (Ortega et al., col. 14, line 20). Consequently, claim 4 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 19, claim 19 recites: “A pharmaceutical combination comprising two or more peptides possessing an amino acid sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.”
Applicant SEQ ID NOs: 1, 14, and 15 are anticipated by Ortega:
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Applicant SEQ ID NO: 2 is also obvious as described above.
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al., col. 4, line 43).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine peptides disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 19 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 20, claim 19 is obvious as described above. Claim 20 further recites the case wherein the peptides are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the peptides of Ortega, Eldeeb, and Mischerikow in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptides of Ortega, Eldeeb, and Mischerikow it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide 1+peptide 2 together are simultaneous, peptide 1 followed by peptide 2 is sequential, and peptide 2 followed by peptide 1 is also sequential. Consequently, claim 20 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Claims 5, 6, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al., US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)).
Regarding claim 5, claim 5 recites: “A pharmaceutical composition for the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system comprising a peptide having an amino acid sequence identified as SEQ ID NO: 1 and a pharmaceutically acceptable excipient.”
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al., col. 4, line 43).
Ortega does not explicitly disclose the usage of the disclosed pharmaceutical composition for the treatment of viruses that infect epithelial cells of the mammalian respiratory system.
However, Ramos discloses that epithelial cells are targeted by respiratory infections in general: “Although endothelial and immune cells express vimentin, not all epithelial cell types, which are the target cell type in respiratory infections, for instance, express this protein, unless they have suffered injury, epithelial-mesenchymal transition or acquire an activated state.” (Ramos et al., page 8, para. 2).
Ortega discloses that SEQ ID NO: 1 has activity that modulates Vimentin in mammalian cells: “Decreased vimentin in the presence of the peptides identified as SEQ ID No. 1, 4, 5, 7, 8 and 9. The MT4 cell line was incubated with said peptides at 50 μM each for 24 h. Vimentin was detected by the western blot technique. Vimentin bands showed a decreased intensity in the cultures treated with the peptides.” (Ortega et al., col. 6, line 53).
Furthermore, Ramos discloses that modulation of Vimentin can affect many diverse virus families: “Vimentin has been shown to play important roles during infection by viruses from multiple families with different types of genomes (DNA, single-stranded RNA, double-stranded RNA, etc.) and replication cycles. Remarkably, there is also great diversity in the viral cycle stages that are impacted by vimentin, with reports ranging from early stages such as binding/entry, fusion or release of virus genome to the cytosol, or later stages such as replication or assembly.” (Ramos, et al., page 9, para. 2). Ramos describes some exemplary viruses such as SARS-CoV2, influenza A, DENV infection, vaccinia virus, hepatitis C, and human Enterovirus Group B. (Ramos, section 6.2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to use the pharmaceutical composition of Ortega to treat a wider variety of viruses that infect epithelial tissue as described by Ramos to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the composition of Ortega in this manner to treat a wider variety of viral targets. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Ortega works through modulating Vimentin in the cytoskeleton and Ramos discloses that modulation of Vimentin can be used to treat a variety of viruses as described above. Consequently, claim 5 is obvious over Ortega et al. in view of Ramos et al. and rejected.
Regarding claim 6, claim 5 is obvious as described above. Claim 6 further recites the case wherein the composition is formulated for administration by the parenteral or mucosal route. Ortega discloses: “Administration routes include the parenteral route and those by which the agent is delivered through the mucosae of the subject.” (Ortega et al., col. 14, line 20). Consequently, claim 6 is obvious over Ortega et al. in view of Ramos et al. and rejected.
Regarding claim 13, claim 13 recites: “A method for the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system, characterized in that said method comprising administering to an individual in need thereof a therapeutically effective amount of at least one peptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.”
Claim 6 of Ortega discloses: “A method of treating HIV infection in a mammal in need thereof, comprising administering to said mammal a therapeutically effective dose of a pharmaceutical composition, said composition comprising a peptide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10 and homologues thereof, said homologues having at least 85% sequence identity with any one of SEQ ID NO: 1 to SEQ ID NO: 10 and having the ability to disrupt, negatively modulate or modify the cytoskeletal IFs in cells of said mammal.”
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega does not disclose the case wherein the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system.
However, Ramos discloses that epithelial cells are targeted by respiratory infections in general: “Although endothelial and immune cells express vimentin, not all epithelial cell types, which are the target cell type in respiratory infections, for instance, express this protein, unless they have suffered injury, epithelial-mesenchymal transition or acquire an activated state.” (Ramos et al., page 8, para. 2).
Furthermore, Ramos discloses that modulation of Vimentin can affect many diverse virus families: “Vimentin has been shown to play important roles during infection by viruses from multiple families with different types of genomes (DNA, single-stranded RNA, double-stranded RNA, etc.) and replication cycles. Remarkably, there is also great diversity in the viral cycle stages that are impacted by vimentin, with reports ranging from early stages such as binding/entry, fusion or release of virus genome to the cytosol, or later stages such as replication or assembly.” (Ramos, et al., page 9, para. 2). Ramos describes some exemplary viruses such as SARS-CoV2, influenza A, DENV infection, vaccinia virus, hepatitis C, and human Enterovirus Group B. (Ramos, section 6.2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to use the method of Ortega to treat a wider variety of viruses that infect epithelial tissue as described by Ramos to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the method of Ortega in this manner to treat a wider variety of viral targets. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Ortega works through modulating Vimentin in the cytoskeleton and Ramos discloses that modulation of Vimentin can be used to treat a variety of viruses as described above. Consequently, claim 13 is obvious over Ortega et al. in view of Ramos et al. and rejected.
Claims 7, 8, 14, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al. , US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) as evidenced by Blümel et al. ( Blümel, Johannes, et al. Transfusion Medicine and Hemotherapy 35.1: 42 (2007)).
Regarding claim 7, claim 5 is obvious as described above. Claim 7 further recites the case wherein the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 7 is obvious over Ortega et al. in view of Ramos et al. as evidenced by Blümel et al. and rejected.
Regarding claim 8, claim 5 is obvious as described above. Claim 8 further recites the case wherein the infection is caused by a virus from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus, and classical swine fever virus.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 8 is obvious over Ortega et al. in view of Ramos et al. as evidenced by Blümel et al. and rejected.
Regarding claim 14, claim 13 is obvious as described above. Claim 14 further recites the case wherein the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 14 is obvious over Ortega et al. in view of Ramos et al. as evidenced by Blümel et al. and rejected.
Regarding claim 15, claim 13 is obvious as described above. Claim 15 further recites the case wherein the infection is caused by a virus from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus, and classical swine fever virus.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 15 is obvious over Ortega et al. in view of Ramos et al. as evidenced by Blümel et al. and rejected.
Claims 16, 17, 18 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al. , US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) as applied to claim 13 above, and further in view of Mahendran, et al. (Mahendran, et al. "The potential of antiviral peptides as COVID-19 therapeutics." Frontiers in pharmacology 11: 575444 (2020)).
Regarding claim 16, claim 13 is obvious as described above. Claim 16 further recites the case wherein an additional antiviral drug is administered to the individual.
Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the method of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the method of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 16 is obvious over Ortega et al. and Ramos et al. as applied to claim 13 above, and further in view of Mahendran et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. Claim 17 further recites the case wherein the peptide and the antiviral drug are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the combination of Ortega, Ramos, and Mahendran in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptide of Ortega and Ramos along with an additional drug disclosed by Mahendran, it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide and drug together are simultaneous, drug followed by peptide is sequential, and peptide followed by drug is also sequential. Consequently, claim 17 is obvious over Ortega et al. and Ramos et al. as applied to claim 13 above, and further in view of Mahendran et al. and rejected.
Regarding claim 18, claim 16 is obvious as described above. Claim 18 further recites the case wherein the antiviral drug is selected from the group consisting of Ribavirin, Ivermectin, Penciclovir, Nitazoxanide, Nafamostat, Remdesivir, Favipiravir, the peptide identified as SEQ ID NO: 23, alpha interferon (IFN), gamma IFN, or a combination of them.
Mahendran et al. discloses the usage of Remdesivir: “Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).”
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the method of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the method of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 18 is obvious over Ortega et al. and Ramos et al. as applied to claim 16 above, and further in view of Mahendran et al. and rejected.
Claims 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al. , US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Mahendran, et al. (Mahendran, et al. "The potential of antiviral peptides as COVID-19 therapeutics." Frontiers in pharmacology 11: 575444 (2020)).
Regarding claim 21, claim 21 recites: “A pharmaceutical combination for the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system, said combination comprising: a) at least one peptide having an amino acid sequence selected from the group consisting of SEQ ID NO : 1 to SEQ ID NO: 20 and b) an antiviral drug.”
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega also discloses: “In another aspect, the present invention provides a pharmaceutical composition for treating or preventing HIV infection, the composition including an agent according to the present invention as described above that disrupts or negatively modulates cytoskeletal IFs according to the present invention as described above, and a pharmaceutically acceptable carrier or excipient.” (Ortega et al., col. 4, line 43).
Ortega does not explicitly disclose the usage of the disclosed pharmaceutical composition for the treatment of viruses that infect epithelial cells of the mammalian respiratory system.
However, Ramos discloses that epithelial cells are targeted by respiratory infections in general: “Although endothelial and immune cells express vimentin, not all epithelial cell types, which are the target cell type in respiratory infections, for instance, express this protein, unless they have suffered injury, epithelial-mesenchymal transition or acquire an activated state.” (Ramos et al., page 8, para. 2).
Ortega discloses that SEQ ID NO: 1 has activity that modulates Vimentin in mammalian cells: “Decreased vimentin in the presence of the peptides identified as SEQ ID No. 1, 4, 5, 7, 8 and 9. The MT4 cell line was incubated with said peptides at 50 μM each for 24 h. Vimentin was detected by the western blot technique. Vimentin bands showed a decreased intensity in the cultures treated with the peptides.” (Ortega et al., col. 6, line 53).
Furthermore, Ramos discloses that modulation of Vimentin can affect many diverse virus families: “Vimentin has been shown to play important roles during infection by viruses from multiple families with different types of genomes (DNA, single-stranded RNA, double-stranded RNA, etc.) and replication cycles. Remarkably, there is also great diversity in the viral cycle stages that are impacted by vimentin, with reports ranging from early stages such as binding/entry, fusion or release of virus genome to the cytosol, or later stages such as replication or assembly.” (Ramos, et al., page 9, para. 2). Ramos describes some exemplary viruses such as SARS-CoV2, influenza A, DENV infection, vaccinia virus, hepatitis C, and human Enterovirus Group B. (Ramos et al., section 6.2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to use the pharmaceutical composition of Ortega to treat a wider variety of viruses that infect epithelial tissue as described by Ramos to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the composition of Ortega in this manner to treat a wider variety of viral targets. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Ortega works through modulating Vimentin in the cytoskeleton and Ramos discloses that modulation of Vimentin can be used to treat a variety of viruses as described above.
Ortega and Ramos do not, in combination, explicitly disclose using an additional anti-viral drug.
However, Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical combination of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the pharmaceutical combination of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 21 is obvious over Ortega et al. in view of Ramos et al. and Mahendran et al. and rejected.
Regarding claim 22, claim 21 is obvious as described above. Claim 22 further recites the case wherein the antiviral drug is selected from the group consisting of Ribavirin, Ivermectin, Penciclovir, Nitazoxanide, Nafamostat, Remdesivir, Favipiravir, the peptide identified as SEQ ID NO: 23, alpha interferon (IFN), gamma IFN, or a combination of them.
Mahendran et al. discloses the usage of Remdesivir: “Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).”
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical combination of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the pharmaceutical combination of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 22 is obvious over Ortega et al. in view of Ramos et al. and Mahendran et al. and rejected.
Regarding claim 23, claim 21 is obvious as described above. Claim 23 further recites the case wherein the peptide and the antiviral drug are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the combination of Ortega, Ramos, and Mahendran in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptide of Ortega and Ramos along with an additional drug disclosed by Mahendran, it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide and drug together are simultaneous, drug followed by peptide is sequential, and peptide followed by drug is also sequential. Consequently, claim 23 is obvious over Ortega et al. in view of Ramos et al. and Mahendran et al. and rejected.
Claims 24 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Ortega et al., US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Mahendran, et al. (Mahendran, et al. "The potential of antiviral peptides as COVID-19 therapeutics." Frontiers in pharmacology 11: 575444 (2020)) as applied to claim 23 above, further evidenced by Blümel et al. ( Blümel, Johannes, et al. Transfusion Medicine and Hemotherapy 35.1: 42 (2007)).
Regarding claim 24, claim 21 is obvious as described above. Claim 25 further recites the case wherein the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 24 is obvious over Ortega et al. in view of Ramos et al. and Mahendren et al. as applied to claim 21, further evidenced by Blümel et al. and rejected.
Regarding claim 25, claim 21 is obvious as described above. Claim 25 further recites the case wherein the infection is caused by a virus from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus, and classical swine fever virus.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 25 is obvious over Ortega et al. in view of Ramos et al. and Mahendren et al. as applied to claim 21, further evidenced by Blümel et al. and rejected.
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 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 9,205,128, published 12/8/2015. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, claim 1 recites a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Consequently, claim 1 is anticipated by Ortega et al. and rejected.
Claim 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 9,205,128, published 12/8/2015 in view of Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)).
Regarding claim 2, claim 2 recites a pharmaceutical composition comprising at least one peptide having an amino sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20 and a pharmaceutically acceptable excipient.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Ortega does not disclose a pharmaceutical excipient in the claims. However, Chaudhari et al. discloses a variety of pharmaceutical excipients and advantages for their use (Chaudhari, page 28 , Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical excipients of Chaudhari with the peptides of Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine them to achieve the advantages disclosed by Chaudhari and have a reasonable expectation of success because Chaudhari describes the extensive use of excipients (Chaudhari, page 21, Introduction).
Consequently, claim 2 is obvious over Ortega et al. in view of Chaudhari et al. and rejected.
Claims 1, 19, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, claim 1 recites a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Consequently, claim 1 is anticipated by Ortega et al. and rejected.
Regarding claim 19, claim 19 recites: “A pharmaceutical combination comprising two or more peptides possessing an amino acid sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.”
Applicant SEQ ID NOs: 1, 14, and 15 are anticipated by Ortega:
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Ortega also discloses in claim 6: “ A method of treating HIV infection in a mammal in need thereof, comprising administering to said mammal a therapeutically effective dose of a pharmaceutical composition, said composition comprising a peptide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10 and homologues thereof…”
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine peptides disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 19 is obvious over Ortega et al. and rejected.
Regarding claim 20, claim 19 is obvious as described above. Claim 20 further recites the case wherein the peptides are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the peptides of Ortega in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptides of Ortega, it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide 1 and peptide 2 together are simultaneous, peptide 1 followed by peptide 2 is sequential, and peptide 2 followed by peptide 1 is also sequential.
Consequently, claim 20 is obvious over Ortega et al. and rejected.
Claims 2 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 9,205,128, published 12/8/2015 in view of Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)).
Regarding claim 2, claim 2 recites a pharmaceutical composition comprising at least one peptide having an amino sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20 and a pharmaceutically acceptable excipient.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Ortega does not disclose a pharmaceutical excipient in the claims. However, Chaudhari et al. discloses a variety of pharmaceutical excipients and advantages for their use (Chaudhari, page 28 , Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical excipients of Chaudhari with the peptides of Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine them to achieve the advantages disclosed by Chaudhari and have a reasonable expectation of success because Chaudhari describes the extensive use of excipients (Chaudhari, page 21, Introduction).
Consequently, claim 2 is obvious over Ortega et al. in view of Chaudhari et al. and rejected.
Regarding claim 3, claim 2 is obvious as described above. Claim 3 recites the case wherein the pharmaceutical composition additionally comprises a peptide having the sequence SEQ ID NO: 1.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical composition of Ortega with SEQ ID NO: 1 disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 3 is obvious over Ortega et al. in view of Chaudhari et al. and rejected.
Claim 4 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 9,205,128, published 12/8/2015 in view of Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)) as applied to claim 2 above, and further in view of Gulati et al. (Gulati, et al. Recent patents on drug delivery & formulation 5.2: 133-145 (2011)).
Regarding claim 4, claim 2 is obvious as described above. Claim 4 further recites the case wherein the composition is formulated for administration by the parenteral or mucosal route.
Gulati et al. discloses: “The parenteral route of administration is the most effective route for the delivery of the active pharmaceutical substances with narrow therapeutic index, poor bioavailability especially for those drugs, prescribed to unconscious patients. To maintain a therapeutic effective concentration of the drug, it requires frequent injections which ultimately lead to patient discomfort. In parenteral drug delivery, major progress has been done in the field of formulation technologies so as to provide a targeted and sustained release of drug in predictable manner.” (Gulati et al, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to deliver the pharmaceutical composition of Ortega and Chaudhari with the parenteral route of Gulati. A person of ordinary skill in the would be motivated to make the combination in the event of poor bioavailability or narrow therapeutic index and have a reasonable expectation of success because Gulati describes it as the most effective route for these conditions. Consequently, claim 4 is obvious over Ortega et al. and Chaudhari et al. as applied to claim 2 above, further in view of Gulati, et al. and rejected.
Claims 1, 19, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view of Eldeeb et al. (Eldeeb, Mohamed A., et al. BioEssays 41.11: 1800167 (2019)) and Mischerikow, et al. (Mischerikow, et al. Proteomics 11.4: 571-589 (2011)).
Regarding claim 1, claim 1 recites a peptide comprising a sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 2:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega et al. does not disclose acetylation at position 1.
However, Eldeeb discloses that N-terminal acetylation stabilizes peptides: “This is exemplified by the observation that indeed Nt-acetylated protein fragments exhibit higher metabolic stability profiles in vivo than non-acetylated counterparts.” (Eldeeb et al., page 5, col. 1, para. 2)
Also, Mischerikow discloses that N-terminal acetylation is extremely common in eukaryotic proteins and peptides: “N-terminal acetylation is one of the most common and abundant protein modifications in eukaryotes, estimated to occur in about 85% of mammalian proteins and 60% of yeast proteins, occurring significantly less frequent in prokaryotes.” (Mischerikow et al., page 572, col. 1, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply N-terminal acetylation to the peptide of Ortega to arrive at the claimed invention. A person of ordinary skill in the would have a reasonable expectation of success due to the frequency of mammalian acetylation disclosed by Mischerikow and would be motivated to achieve the increased stability as described by Eldeeb. Consequently, claim 1 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 19, claim 19 recites: “A pharmaceutical combination comprising two or more peptides possessing an amino acid sequence that is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.”
Applicant SEQ ID NOs: 1, 14, and 15 are anticipated by Ortega:
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 14:
Sequence 18 AA;
Query Match 100.0%; Score 55; Length 18;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NDRLASLYDKV 11
|||||||||||
Db 8 NDRLASLYDKV 18
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 15:
SQ Sequence 18 AA;
Query Match 100.0%; Score 65; Length 18;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NLNDRLASLYDKV 13
|||||||||||||
Db 6 NLNDRLASLYDKV 18
Applicant SEQ ID NO: 2 is also obvious as described above.
Ortega also discloses in claim 6: “ A method of treating HIV infection in a mammal in need thereof, comprising administering to said mammal a therapeutically effective dose of a pharmaceutical composition, said composition comprising a peptide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10 and homologues thereof…”
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine peptides disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 19 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Regarding claim 20, claim 19 is obvious as described above. Claim 20 further recites the case wherein the peptides are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the peptides of Ortega, Eldeeb, and Mischerikow in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptides of Ortega, Eldeeb, and Mischerikow it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide 1+peptide 2 together are simultaneous, peptide 1 followed by peptide 2 is sequential, and peptide 2 followed by peptide 1 is also sequential. Consequently, claim 20 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. and rejected.
Claims 2 and 3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view of Eldeeb et al. (Eldeeb, Mohamed A., et al. BioEssays 41.11: 1800167 (2019)) and Mischerikow, et al. (Mischerikow, et al. Proteomics 11.4: 571-589 (2011)) as applied to claim 1 above, further in view of Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)).
Regarding claim 2, claim 2 recites a pharmaceutical composition comprising at least one peptide having an amino sequence selected from the group consisting of SEQ ID NO: 2 to SEQ ID NO: 20 and a pharmaceutically acceptable excipient.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 2:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega et al. 2 does not disclose acetylation at position 1.
However, Eldeeb discloses that N-terminal acetylation stabilizes peptides: “This is exemplified by the observation that indeed Nt-acetylated protein fragments exhibit higher metabolic stability profiles in vivo than non-acetylated counterparts.” (Eldeeb et al., page 5, col. 1, para. 2)
Also, Mischerikow discloses that N-terminal acetylation is extremely common in eukaryotic proteins and peptides: “N-terminal acetylation is one of the most common and abundant protein modifications in eukaryotes, estimated to occur in about 85% of mammalian proteins and 60% of yeast proteins, occurring significantly less frequent in prokaryotes.” (Mischerikow et al., page 572, col. 1, para. 3).
Ortega does not disclose a pharmaceutical excipient in the claims. However, Chaudhari et al. discloses a variety of pharmaceutical excipients and advantages for their use (Chaudhari, page 28 , Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical excipients of Chaudhari with the peptides of Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine them to achieve the advantages disclosed by Chaudhari and have a reasonable expectation of success because Chaudhari describes the extensive use of excipients (Chaudhari, page 21, Introduction).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply N-terminal acetylation to the peptide and pharmaceutically acceptable excipient of Ortega to arrive at the claimed invention. A person of ordinary skill in the would have a reasonable expectation of success due to the frequency of mammalian acetylation disclosed by Mischerikow and would be motivated to achieve the increased stability as described by Eldeeb.
Consequently, claim 2 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. as applied to claim 1 above, further in view of Chaudhari et al. and rejected.
Regarding claim 3, claim 2 is obvious as described above. Claim 3 recites the case wherein the pharmaceutical composition additionally comprises a peptide having the sequence SEQ ID NO: 1.
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical composition of Ortega, Eldeeb, Chaudhari, and Mischerikow with SEQ ID NO: 1 disclosed by Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine the peptides because they share the same core structure of NDRLASLYDKV, and therefore reasonably share functionality.
MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven”.
A person of ordinary skill in the art would have a reasonable expectation of success of achieving a combined effect due to the shared core sequence structure. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Consequently, claim 3 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. as applied to claim 1 above, further in view of Chaudhari et al. and rejected.
Claim 4 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view of Eldeeb et al. (Eldeeb, Mohamed A., et al. BioEssays 41.11: 1800167 (2019)) and Mischerikow, et al. (Mischerikow, et al. Proteomics 11.4: 571-589 (2011)) as applied to claim 1 above, further in view of Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)) as applied to claim 2, further in view of Gulati et al. (Gulati, et al. Recent patents on drug delivery & formulation 5.2: 133-145 (2011)).
Regarding claim 4, claim 2 is obvious as described above. Claim 4 further recites the case wherein the composition is formulated for administration by the parenteral or mucosal route.
Gulati et al. discloses: “The parenteral route of administration is the most effective route for the delivery of the active pharmaceutical substances with narrow therapeutic index, poor bioavailability especially for those drugs, prescribed to unconscious patients. To maintain a therapeutic effective concentration of the drug, it requires frequent injections which ultimately lead to patient discomfort. In parenteral drug delivery, major progress has been done in the field of formulation technologies so as to provide a targeted and sustained release of drug in predictable manner.” (Gulati et al, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to deliver the pharmaceutical composition of Ortega and Chaudhari with the parenteral route of Gulati. A person of ordinary skill in the would be motivated to make the combination in the event of poor bioavailability or narrow therapeutic index and have a reasonable expectation of success because Gulati describes it as the most effective route for these conditions.
Consequently, claim 4 is obvious over Ortega et al. in view of Eldeeb et al. and Mischerikow et al. as applied to claim 1 above, further in view of Chaudhari et al as applied to claim 2 above, further in view of Gulati, et al. and rejected.
Claims 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)).
Regarding claim 5, claim 5 recites: “A pharmaceutical composition for the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system comprising a peptide having an amino acid sequence identified as SEQ ID NO: 1 and a pharmaceutically acceptable excipient.”
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega does not disclose a pharmaceutical excipient in the claims. However, Chaudhari et al. discloses a variety of pharmaceutical excipients and advantages for their use (Chaudhari, page 28 , Table 2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical excipients of Chaudhari with the peptides of Ortega to arrive at the claimed invention. A person of ordinary skill in the art would be motivated to combine them to achieve the advantages disclosed by Chaudhari and have a reasonable expectation of success because Chaudhari describes the extensive use of excipients (Chaudhari, page 21, Introduction).
Ortega does not explicitly disclose the usage of the disclosed pharmaceutical composition for the treatment of viruses that infect epithelial cells of the mammalian respiratory system.
However, Ramos discloses that epithelial cells are targeted by respiratory infections in general: “Although endothelial and immune cells express vimentin, not all epithelial cell types, which are the target cell type in respiratory infections, for instance, express this protein, unless they have suffered injury, epithelial-mesenchymal transition or acquire an activated state.” (Ramos et al., page 8, para. 2).
Ortega claim 1 discloses: “A method to inhibit the replication of the human immunodeficiency virus (HIV) comprising disrupting the structure of cytoskeletal intermediate filaments (IFs) in a mammalian cell, wherein said disruption of IFs is achieved by administering to a human subject in need thereof a peptide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10 and homologues thereof, said homologues having at least 85% sequence identity with any one of SEQ ID NO: 1 to SEQ ID NO: 10 and having the ability to disrupt, negatively modulate or modify the cytoskeletal IFs in said mammalian cell.”
Ortega claim 2 discloses: “The method according to claim 1 wherein said IFs comprise vimentin and/or keratin proteins.”
Furthermore, Ramos discloses that modulation of Vimentin can affect many diverse virus families: “Vimentin has been shown to play important roles during infection by viruses from multiple families with different types of genomes (DNA, single-stranded RNA, double-stranded RNA, etc.) and replication cycles. Remarkably, there is also great diversity in the viral cycle stages that are impacted by vimentin, with reports ranging from early stages such as binding/entry, fusion or release of virus genome to the cytosol, or later stages such as replication or assembly.” (Ramos, et al., page 9, para. 2). Ramos describes some exemplary viruses such as SARS-CoV2, influenza A, DENV infection, vaccinia virus, hepatitis C, and human Enterovirus Group B. (Ramos, section 6.2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to use the pharmaceutical composition of Ortega to treat a wider variety of viruses that infect epithelial tissue as described by Ramos to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the composition of Ortega in this manner to treat a wider variety of viral targets. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Ortega works through modulating Vimentin in the cytoskeleton and Ramos discloses that modulation of Vimentin can be used to treat a variety of viruses as described above. Consequently, claim 5 is obvious over Ortega et al. in view of Ramos et al. and Chaudhari et al. and rejected.
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)) as applied to claim 5 above, and further in view of Gulati et al. (Gulati, et al. Recent patents on drug delivery & formulation 5.2: 133-145 (2011)).
Regarding claim 6, claim 5 is obvious as described above. Claim 6 further recites the case wherein the composition is formulated for administration by the parenteral or mucosal route.
Gulati et al. discloses: “The parenteral route of administration is the most effective route for the delivery of the active pharmaceutical substances with narrow therapeutic index, poor bioavailability especially for those drugs, prescribed to unconscious patients. To maintain a therapeutic effective concentration of the drug, it requires frequent injections which ultimately lead to patient discomfort. In parenteral drug delivery, major progress has been done in the field of formulation technologies so as to provide a targeted and sustained release of drug in predictable manner.” (Gulati et al, Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to deliver the pharmaceutical composition of Ortega and Chaudhari with the parenteral route of Gulati. A person of ordinary skill in the would be motivated to make the combination in the event of poor bioavailability or narrow therapeutic index and have a reasonable expectation of success because Gulati describes it as the most effective route for these conditions.
Consequently, claim 6 is obvious over Ortega et al. in view of Ramos et al. and Chaudhari et al. as applied to claim 5 above, further in view of Gulati et al. and rejected.
Claims 7, 8, 14, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Chaudhari et al. (Chaudhari, et al. Int J Adv Pharm Biol Chem 1.1: 21-34 (2012)) as applied to claim 5 above, and further in view of Gulati et al. (Gulati, et al. Recent patents on drug delivery & formulation 5.2: 133-145 (2011)) as evidenced by Blümel et al. ( Blümel, Johannes, et al. Transfusion Medicine and Hemotherapy 35.1: 42 (2007)).
Regarding claim 7, claim 5 is obvious as described above. Claim 7 further recites the case wherein the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 7 is obvious over Ortega et al. in view of Ramos et al., Chaudhari et al., and Gulati et al. as evidenced by Blümel et al. and rejected.
Regarding claim 8, claim 5 is obvious as described above. Claim 8 further recites the case wherein the infection is caused by a virus from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus, and classical swine fever virus.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 7 is obvious over Ortega et al. in view of Ramos et al., Chaudhari et al., and Gulati et al. as evidenced by Blümel et al. and rejected.
Claim 13 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view and Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020))
Regarding claim 13, claim 13 recites: “A method for the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system, characterized in that said method comprising administering to an individual in need thereof a therapeutically effective amount of at least one peptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 20.”
Claim 6 of Ortega discloses: “A method of treating HIV infection in a mammal in need thereof, comprising administering to said mammal a therapeutically effective dose of a pharmaceutical composition, said composition comprising a peptide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10 and homologues thereof, said homologues having at least 85% sequence identity with any one of SEQ ID NO: 1 to SEQ ID NO: 10 and having the ability to disrupt, negatively modulate or modify the cytoskeletal IFs in cells of said mammal.”
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
||||||||||||||||||
Db 1 RVTQMNLNDRLASLYDKV 18
Ortega does not disclose the case wherein the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system.
However, Ramos discloses that epithelial cells are targeted by respiratory infections in general: “Although endothelial and immune cells express vimentin, not all epithelial cell types, which are the target cell type in respiratory infections, for instance, express this protein, unless they have suffered injury, epithelial-mesenchymal transition or acquire an activated state.” (Ramos et al., page 8, para. 2).
Ortega claim 2 discloses: “The method according to claim 1 wherein said IFs comprise vimentin and/or keratin proteins.”
Furthermore, Ramos discloses that modulation of Vimentin can affect many diverse virus families: “Vimentin has been shown to play important roles during infection by viruses from multiple families with different types of genomes (DNA, single-stranded RNA, double-stranded RNA, etc.) and replication cycles. Remarkably, there is also great diversity in the viral cycle stages that are impacted by vimentin, with reports ranging from early stages such as binding/entry, fusion or release of virus genome to the cytosol, or later stages such as replication or assembly.” (Ramos, et al., page 9, para. 2). Ramos describes some exemplary viruses such as SARS-CoV2, influenza A, DENV infection, vaccinia virus, hepatitis C, and human Enterovirus Group B. (Ramos, section 6.2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to use the method of Ortega to treat a wider variety of viruses that infect epithelial tissue as described by Ramos to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the method of Ortega in this manner to treat a wider variety of viral targets. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Ortega works through modulating Vimentin in the cytoskeleton and Ramos discloses that modulation of Vimentin can be used to treat a variety of viruses as described above. Consequently, claim 13 is obvious over Ortega et al. in view of Ramos et al. and rejected.
Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of U.S. Patent No. US 9,205,128, published 12/8/2015, in view Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) as applied to claim 13, further evidenced by Blümel et al. ( Blümel, Johannes, et al. Transfusion Medicine and Hemotherapy 35.1: 42 (2007)).
Regarding claim 14, claim 13 is obvious as described above. Claim 14 further recites the case wherein the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 14 is obvious over Ortega et al. in view of Ramos et al., as evidenced by Blümel et al. and rejected.
Regarding claim 15, claim 13 is obvious as described above. Claim 15 further recites the case wherein the infection is caused by a virus from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus, and classical swine fever virus.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 15 is obvious over Ortega et al. in view of Ramos et al. as evidenced by Blümel et al. and rejected.
Claims 16, 17, 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of Ortega et al., US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) as applied to claim 13 above, and further in view of Mahendran, et al. (Mahendran, et al. "The potential of antiviral peptides as COVID-19 therapeutics." Frontiers in pharmacology 11: 575444 (2020)).
Regarding claim 16, claim 13 is obvious as described above. Claim 16 further recites the case wherein an additional antiviral drug is administered to the individual.
Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the method of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the method of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 16 is obvious over Ortega et al. and Ramos et al. as applied to claim 13 above, and further in view of Mahendran et al. and rejected.
Regarding claim 17, claim 16 is obvious as described above. Claim 17 further recites the case wherein the peptide and the antiviral drug are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the combination of Ortega, Ramos, and Mahendran in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptide of Ortega and Ramos along with an additional drug disclosed by Mahendran, it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide and drug together are simultaneous, drug followed by peptide is sequential, and peptide followed by drug is also sequential. Consequently, claim 17 is obvious over Ortega et al. and Ramos et al. as applied to claim 13 above, and further in view of Mahendran et al. and rejected.
Regarding claim 18, claim 16 is obvious as described above. Claim 18 further recites the case wherein the antiviral drug is selected from the group consisting of Ribavirin, Ivermectin, Penciclovir, Nitazoxanide, Nafamostat, Remdesivir, Favipiravir, the peptide identified as SEQ ID NO: 23, alpha interferon (IFN), gamma IFN, or a combination of them.
Mahendran et al. discloses the usage of Remdesivir: “Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).”
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the method of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the method of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 18 is obvious over Ortega et al. and Ramos et al. as applied to claim 16 above, and further in view of Mahendran et al. and rejected.
Claims 21-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of Ortega et al., US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Mahendran, et al. (Mahendran, et al. "The potential of antiviral peptides as COVID-19 therapeutics." Frontiers in pharmacology 11: 575444 (2020)).
Regarding claim 21, claim 21 recites: “A pharmaceutical combination for the treatment or prevention of infections caused by viruses that infect epithelial cells of the mammalian respiratory system, said combination comprising: a) at least one peptide having an amino acid sequence selected from the group consisting of SEQ ID NO : 1 to SEQ ID NO: 20 and b) an antiviral drug.”
Ortega discloses SEQ ID NO: 1, aligned below with Applicant SEQ ID NO: 1:
SQ Sequence 18 AA;
Query Match 100.0%; Score 89; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVTQMNLNDRLASLYDKV 18
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Db 1 RVTQMNLNDRLASLYDKV 18
Claim 6 of Ortega discloses: “A method of treating HIV infection in a mammal in need thereof, comprising administering to said mammal a therapeutically effective dose of a pharmaceutical composition, said composition comprising a peptide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 10 and homologues thereof, said homologues having at least 85% sequence identity with any one of SEQ ID NO: 1 to SEQ ID NO: 10 and having the ability to disrupt, negatively modulate or modify the cytoskeletal IFs in cells of said mammal.”
Ortega does not explicitly disclose the usage of the disclosed pharmaceutical composition for the treatment of viruses that infect epithelial cells of the mammalian respiratory system.
However, Ramos discloses that epithelial cells are targeted by respiratory infections in general: “Although endothelial and immune cells express vimentin, not all epithelial cell types, which are the target cell type in respiratory infections, for instance, express this protein, unless they have suffered injury, epithelial-mesenchymal transition or acquire an activated state.” (Ramos et al., page 8, para. 2).
Ortega claim 2 discloses: “The method according to claim 1 wherein said IFs comprise vimentin and/or keratin proteins.”
Furthermore, Ramos discloses that modulation of Vimentin can affect many diverse virus families: “Vimentin has been shown to play important roles during infection by viruses from multiple families with different types of genomes (DNA, single-stranded RNA, double-stranded RNA, etc.) and replication cycles. Remarkably, there is also great diversity in the viral cycle stages that are impacted by vimentin, with reports ranging from early stages such as binding/entry, fusion or release of virus genome to the cytosol, or later stages such as replication or assembly.” (Ramos, et al., page 9, para. 2). Ramos describes some exemplary viruses such as SARS-CoV2, influenza A, DENV infection, vaccinia virus, hepatitis C, and human Enterovirus Group B. (Ramos et al., section 6.2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to use the pharmaceutical composition of Ortega to treat a wider variety of viruses that infect epithelial tissue as described by Ramos to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use the composition of Ortega in this manner to treat a wider variety of viral targets. A person of ordinary skill in the art would have a reasonable expectation of success because the peptide of Ortega works through modulating Vimentin in the cytoskeleton and Ramos discloses that modulation of Vimentin can be used to treat a variety of viruses as described above.
Ortega and Ramos do not, in combination, explicitly disclose using an additional anti-viral drug.
However, Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical combination of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the pharmaceutical combination of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 21 is obvious over Ortega et al. in view of Ramos et al. and Mahendran et al. and rejected.
Regarding claim 22, claim 21 is obvious as described above. Claim 22 further recites the case wherein the antiviral drug is selected from the group consisting of Ribavirin, Ivermectin, Penciclovir, Nitazoxanide, Nafamostat, Remdesivir, Favipiravir, the peptide identified as SEQ ID NO: 23, alpha interferon (IFN), gamma IFN, or a combination of them.
Mahendran et al. discloses the usage of Remdesivir: “Mahendran et al. discloses that remdesivir is known to be a treatment candidate for COVID-19 (a coronavirus): “To name a few, these include the nucleoside inhibitor prodrug remdesivir (GS-5734), the antiparasitic drug ivermectin, the HIV protease inhibitor nelfinavir, the anti-inflammatory drug cepharanthine, the antimalarial drug hydroxychloroquine, the general steroid dexamethasone, and others.” (Mahendran, et al., page 1, Introduction).”
Furthermore, Mahendran discloses that such treatments can be combined with anti-viral peptides: “Cocktail therapy using a selected combination of AVPs or as supplemental therapeutics in combination with other classes of antiviral agents could be a promising treatment strategy that would worth further clinical investigations (Vilas Boas et al., 2019). Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the pharmaceutical combination of Ortega and Ramos with an additional antiviral drug as disclosed by Mahendran to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to add an additional antiviral drug to the pharmaceutical combination of Ortega and Ramos to achieve and additive or perhaps even synergistic effect. Furthermore, MPEP 2144.06(I) states: “"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).”
A person of ordinary skill in the art would have a reasonable expectation of success because Mahendran provides at least one example of an anti-viral drug peptide combination: “Such optimism is not unfounded, as enfuvirtide, a 36-amino acid fusion inhibitor AVP, was approved by the US Food and Drug Administration in 2003 for treatment against human immunodeficiency virus in combination with other antiretroviral drugs (Lalezari et al., 2003; Fung and Guo, 2004; Poveda et al., 2005).” (Mahendran, et al. page 4, col. 2, para. 1).
Consequently, claim 22 is obvious over Ortega et al. in view of Ramos et al. and Mahendran et al. and rejected.
Regarding claim 23, claim 21 is obvious as described above. Claim 23 further recites the case wherein the peptide and the antiviral drug are administered simultaneously or sequentially.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer the combination of Ortega, Ramos, and Mahendran in either a sequential or simultaneous manner and therefore arrive at the claimed invention.
When administering the peptide of Ortega and Ramos along with an additional drug disclosed by Mahendran, it is necessarily true that these will be administered either together at one time or one after another. Any possible dosage regime will fall into one of these two categories: peptide and drug together are simultaneous, drug followed by peptide is sequential, and peptide followed by drug is also sequential. Consequently, claim 23 is obvious over Ortega et al. in view of Ramos et al. and Mahendran et al. and rejected.
Claims 24 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of Ortega et al., US 9,205,128, published 12/8/2015, in view of Ramos et al. (Ramos, et al. International journal of molecular sciences 21.13: 4675 (2020)) and Mahendran, et al. (Mahendran, et al. "The potential of antiviral peptides as COVID-19 therapeutics." Frontiers in pharmacology 11: 575444 (2020)) as applied to claim 23 above, further evidenced by Blümel et al. ( Blümel, Johannes, et al. Transfusion Medicine and Hemotherapy 35.1: 42 (2007)).
Regarding claim 24, claim 21 is obvious as described above. Claim 25 further recites the case wherein the infection is caused by a virus of the coronaviridae, ortho- and para-myxoviridae, picornaviridae and adenoviridae families.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 24 is obvious over Ortega et al. in view of Ramos et al. and Mahendren et al. as applied to claim 21, further evidenced by Blümel et al. and rejected.
Regarding claim 25, claim 21 is obvious as described above. Claim 25 further recites the case wherein the infection is caused by a virus from the group consisting of coronavirus, influenza virus, parainfluenza, respiratory syncytial virus, adenovirus, dengue virus, herpes simplex virus, cytomegalovirus, and classical swine fever virus.
Blümel discloses that: “Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans.”
Influenza A is disclosed by Ramos as target for treatment via Vimentin modulation: “In the case of influenza A virus (IAV), it has been shown that vimentin is necessary for the release of viral ribonucleoproteins (vRNPs) to the cytoplasm through alteration of lysosomal trafficking during entry (Figure 2C). This effect seems to be associated with impaired acidification of early endosomes in cells lacking vimentin, which is necessary for membrane fusion during early stages of infection, resulting in defective release of vRNPs to the cytoplasm.” (Ramos et al., page 10, para. 3).
Consequently, claim 25 is obvious over Ortega et al. in view of Ramos et al. and Mahendren et al. as applied to claim 21, further evidenced by Blümel et al. and rejected.
Conclusion
No claim is allowed.
Claims 1-8 and 13-25 are rejected.
Claim 5, 18, 19, and 22 are objected to.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654