DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 15-27 drawn to a method of treating a disease caused by an intracellular pathogen by providing a CD1 peptide-epitope, an activated form of the intracellular pathogen, and a second peptide based on a protein of the intracellular pathogen) in the reply filed on 09/17/2025 is acknowledged. Additionally, Applicant’s election without traverse of a species of intracellular pathogen (i.e., Flaviviridae) in the reply filed on 09/17/2025 is also acknowledged.
Claims 28-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/17/2025.
Upon searching the elected species (i.e., Flaviviridae), additional species were found, e.g., Herpesviridae and Picornaviridae. Accordingly, for purposes of compact prosecution, the election of species is modified only to the extent of examining these additional species. Otherwise the election of species requirement is still retained.
Priority
The present application claims status as a 371 (National Stage) of PCT/EP2021/068585 filed July 6th 2021, and claims priority under 119(a)-(d) to European Application No. EP20184175.6 filed on July 6th 2020.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for European Application No. EP20184175.6, which papers have been placed of record in the file. Please note that the European application is in English and therefore no further action is needed.
Status of Claims
Claims 1-14 were originally filed on 01/03/2023.
The amendment filed on 04/03/2023 cancelled claims 1-14 and added new claims 15-34.
Information Disclosure Statement
The IDSs filed on 01/09/2023 and 05/27/2025 have been considered by the Examiner.
Claim Interpretation/Sequence Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 15, regarding the scope of “…in the prevention of the disease”, it is noted that the instant specification does not define what constitutes “prevention” of a disease. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The Merriam Webster Dictionary defines “prevention” as to keep from happening or existing (see Merriam-Webster, “Prevent”, available at https://www.merriam-webster.com/dictionary/prevent, at pg. 1, accessed on 01/05/2026). As such, the Examiner is interpreting the scope of “prevention” as encompassing 100% prevention of the disease.
Similarly, regarding the scope of “…in the treatment of the disease” it is noted that the instant specification does not define what constitutes “treatment” of a disease. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The Merriam-Webster Dictionary, defines “treating” as a to act upon with some agent especially to improve or alter (see Merriam-Webster Dictionary, “treating,” available online at https://www.merriam-webster.com/dictionary/treat#:~:text=%3A%20to%20care%20for%20or%20deal,treat%20a%20metal%20with%20acid on 01/12/2025). As such, the Examiner is interpreting the scope of “treatment of the disease” as improving or altering the disease by administering a CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7, where X1 and X7 are independently F, W, T, H, or Y; and X2, X3, X4, X5 , independently stand for any amino acid. However the improving or altering does not encompass 100% prevention.
With respect to the CD1 peptide-epitope, the Examiner is interpreting the scope of the “CD1 peptide-epitope” as a peptide fragment of unspecified length derived from any protein expressed by any intracellular pathogen, comprises the sequence X1X2X3X4X5X6X7, with any N-/C- terminal additions, insertions, substitutions, deletions, etc., binds to a CD1 molecule; and exhibits the function of preventing or treating any disease, wherein the disease is caused by any intracellular pathogen.
Claim Objections
Applicant is advised that claim 22 includes an identical recitation of the claim limitations recited in claim 19; and should claim 19 be found allowable, claim 22 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). In particular, lines 1-2 in claim 22 recite duplicate limitations of the limitations recited in lines 1-2 in claim 19; therefore, claim 22 is found to be a duplicate of claim 19.
Applicant is advised that claim 23 includes an identical recitation of the claim limitations recited in claim 20; and should claim 20 be found allowable, claim 23 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). In particular, lines 1-2 in claim 23 recite duplicate limitations of the limitations recited in lines 1-2 in claim 20; therefore, claim 23 is found to be a duplicate of claim 20.
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.
1. Claims 15-27 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. In the instant case, claim 15 is drawn to “a method of treating a disease comprising: providing a CD1 peptide-epitope […], wherein the CD1 peptide-epitope is a fragment of a protein expressed by the intracellular pathogen […]; and administering at least one of: an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope…” However, it has not been clearly defined and/or established whether the CD1 peptide-epitope and the second peptide are derived from and/or based on the same protein of the intracellular pathogen. Therefore, an ordinary skilled artisan would not be able to determine whether the protein expressed by the intracellular pathogen from which the CD1 peptide-epitope fragment is derived, is the same as the protein of said intracellular pathogen from which a second peptide is based; nor whether the protein of said intracellular pathogen from which the second peptide is based is also expressed; nor whether the second peptide is a fragment or a full length peptide of said intracellular pathogen from; nor whether the second peptide is based on a protein from a different intracellular pathogen. As such, claim 15 and dependent claims 16-27 are indefinite.
2. Claims 15-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 15 recites the limitation “CD1 epitope-epitope” in line 14. There is insufficient antecedent basis for this limitation in the claim. The claim only recites that the CD1 peptide-epitope is a fragment of a protein expressed by the intracellular pathogen. However the claim fails to recite whether the second peptide based on a protein of said intracellular pathogen also comprises a second epitope thus resulting in the CD1 epitope-epitope; or whether the second epitope in the CD1 epitope-epitope refers to the MHC Class I epitope. In order to advance prosecution, the Examiner is interpreting the second peptide as comprising the CD1 peptide-epitope and at least one MHC Class I epitope.
3. Claims 24-27 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. In the instant case, claims 24-27 are directly dependent on a cancelled claim (i.e., claim 1), therefore the claims are indefinite because they fail to further limit the base claim (i.e., claim 1).
4. Claims 15-27 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. In the instant case, claim 15 recites administering “a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 epitope-epitope and at least one MHC Class I epitope.” However, if the second peptide is administered after the CD1 peptide-epitope, it is unclear and/or ambiguous as to whether the second peptide comprises the same CD1 peptide-epitope or a different peptide-epitope which comprises two epitopes (i.e., CD1 epitope-epitope), and if so, the which epitopes are comprised by the doble epitope CD1 peptide. An ordinary skilled artisan would not be able to ascertain the metes and bounds of the claimed invention with respect to the second peptide. As such, claims 15-27 are indefinite. In order to advance prosecution, said second peptide is being interpreted as comprising the CD1 peptide-epitope and at least one MHC Class I epitope.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
5. Claims 24-27 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 24 is drawn to the method according to claim 1, thus the claim is dependent upon claim 1. However, claim 1 was cancelled in the amendment filed on 04/03/2023. Claims 25-27 are also rejected because of their dependency on claim 24, which fails to further limit the subject matter of the cancelled claimed (i.e., claim 1). In order to advance prosecution, the Examiner is interpreting claim 24 as the method of claim 15. Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
6. Claims 15-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus.
Independent claim 15 is drawn to “a method of treating a disease, comprising: providing a CD1 peptide-epitope for use in the prevention or in the treatment of the disease, wherein the disease is caused by an intracellular pathogen, wherein the CD1 peptide-epitope is a fragment of a protein expressed by the intracellular pathogen, wherein:
said CD1 peptide-epitope includes the sequence X1X2X3X4X5X6X7; said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y; administering the CD1 peptide-epitope to a subject having the disease;
and administering at least one of: an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 epitope-epitope and at least one MHC Class I epitope.”
As discussed in the “Claim/Sequence Interpretation” section above, the Examiner interprets the scope of the “CD1 peptide-epitope” as a peptide fragment of unspecified length derived from any protein expressed by any intracellular pathogen, comprises the sequence X1X2X3X4X5X6X7, with any N-/C- terminal additions, insertions, substitutions, deletions, etc., binds to a CD1 molecule and exhibits the function of preventing or treating any disease, wherein the disease is caused by any intracellular pathogen. As such, the scope of the claimed method of treating a disease encompasses any disease caused by any intracellular pathogen, any CD1 peptide-epitope fragment of any protein expressed by any intracellular pathogen, any inactivated form of the intracellular pathogen and any second peptide based on any protein of any intracellular pathogen. Therefore, the scope of claim 15 and dependent claims 16 and 18-27 encompass a vast array of CD1 peptide-epitopes for use in the prevention or in the treatment of the disease without a necessary core structure and/or sequence that would be needed for the CD1 peptide-epitope to prevent or treat any disease caused by any intracellular pathogen.
The instant specification teaches that the pathogen is Dengue virus and the CD1 peptide-epitope is a fragment of an NS protein, preferably NS5 and comprising or consisting of the sequence set forth in SEQ ID NO:1 (see instant specification, pg. 14, lines 29-31). Preferably, the CD1 peptide-epitope is between 11 and 50 amino acids in length, such as between 11 and 40, or between 11 and 30, or between 11 and 20 amino acids in length; and that the second peptide is a full-length NS5 protein (see instant specification, pg. 14, lines 32-35).
In another embodiment, the pathogen is Coxsackie B4 virus and the CD1 peptide-epitope is a fragment of the polyprotein, preferably comprising or consisting of the sequence set forth in SEQ ID NO:2 (see instant specification, pg. 15, lines 1-3). Preferably, the CD1 peptide-epitope is between 11 and 50 amino acids in length, such as between 11 and 40, or between 11 and 30, or between 11 and 20 amino acids in length, and that in a further embodiment hereof, the second peptide is a full-length polyprotein (see instant specification, pg. 15, lines 4-6).
In another embodiment, the pathogen is SARS-CoV2 virus and the CD1 peptide-epitope is a fragment of the S protein, preferably comprising or consisting of the sequence set forth in SEQ ID NO:3 (see instant specification, pg. 15, lines 9-11). Preferably, the CD1 peptide-epitope is between 11 and 50 amino acids in length, such as between 11 and 40, or between 11 and 30, or between 11 and 20 amino acids in length; and that in a further embodiment hereof, the second peptide is a full-length S protein. (see instant specification, pg. 15, lines 12-15).
In another embodiment, the pathogen is influenza A virus and the CD1 peptide-epitope is a fragment of the hemagglutinin protein, preferably comprising or consisting of the sequence set forth in
SEQ ID NO:4 (see instant specification, pg. 15, lines 17-20). Preferably, the CD1 peptide-epitope is between 11 and 50 amino acids in length, such as between 11 and 40, or between 11 and 30, or between 11 and 20 amino acids in length; and that in further embodiment hereof, the second peptide is a full-length hemagglutinin (see instant specification, pg. 15, lines 20-24).
In another embodiment, the pathogen is herpes simplex virus and the CD1 peptide-epitope is a fragment of the Vp16 protein, preferably comprising or consisting of the sequence set forth in SEQ ID NO:5 (see instant specification, pg. 15, lines 26-28). Preferably, the CD1 peptide-epitope is between 11 and 50 amino acids in length, such as between 11 and 4 0, or between 11 and 30, or between 11 and 20 amino acids in length; and that in a further embodiment hereof, the vaccination is with a live-inactivated HSV vaccine (see instant specification, pg. 15, lines 29-32).
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. MPEP 2163 (I)(A). The sequences reduced to practice (i.e., SEQ ID NOs: 1-5) do not share a common core structure; without an indication of a core structure, sequence or residues that would be necessary in order for a sequence to exhibit the claimed function (i.e., prevention or treatment of the disease), it would be difficult for a skilled artisan to envision the correlation between structure and function for the whole genus and/or to predict what would be covered by the functionally claimed genus because Applicants have failed to provide a representative number of species to support the scope of the whole genus (i.e., a method of treating any disease caused by any intracellular pathogen, comprising any CD1 peptide-epitope, any fragment of any protein expressed by any intracellular pathogen and any second peptide based on any protein of any intracellular pathogen).
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Lei et al., teach that in the design of epitope-based vaccines, researchers generally regard the application of built-in adjuvants as an important platform used to provide suitable Th-cell epitopes for specific pathogens or pathogen related molecular patterns (PAMPs) to activate the innate immune response (see Lei et al., Peer J, 2019, e6, pp 1-48, at pg. 4, first paragraph). Lei et al. also teach that some molecular adjuvants or carriers with no infectious and toxic components can be used as built-in adjuvants to facilitate the presentation of pathogen epitopes to the immune system (see Lei at al. pg. 4, first paragraph). Lei et al.’s Table 5 teaches different investigational built in adjuvants for epitope-based vaccines according to the disease (see Lei et al., pp. 24-25). Lei et al. conclude that to overcome the obstacles associated with epitope-based vaccines (e.g., enzymatic degradation), facilitate recognition by the target cells of the immune system more efficiently, as well as maintain and enhance the efficiency and immunoreactivity of the constructed vaccines, the development of novel built-in adjuvants is a key step in the design of epitope-based vaccines (see Lei et al., pg. 27, second paragraph). .
Therefore, Lei et al.’s teachings present compelling evidence stablishing the functional identities when designing epitope vaccines and the types of built-in adjuvants typically considered include: (1) pattern recognition receptor ligands (i.e., toll-like receptors); (2) virus-like particle carrier platforms; (3) bacterial toxin proteins; and (4) novel potential delivery systems (e.g., self-assembled peptide nanoparticles, lipid core peptides, and polymeric or inorganic nanoparticles) (see Lei et al. pg. 1, abstract). Thus, the instant claims are directed to a method of treating a disease comprising a fragment of a protein expressed by an intracellular pathogen (i.e., CD1 peptide-epitope), an inactivated form of the intracellular pathogen or a second peptide based on a protein of said intracellular pathogen, a with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by providing a representative number of species of the genus. In the instant case, specification teaches at pp. 18-25, Examples 1-5, wherein mice are immunized with the peptide of SEQ ID NO: 1 (i.e., Dengue virus infection) or SEQ ID NO: 2 (Coxsackie B4 infection) or SEQ ID NO: 3 (i.e., SARS-CoV-2 infection) or SEQ ID NO: 4 (i.e., Influenza Virus infection) or SEQ ID NO: 5 (i.e., Herpes Simplex Virus infection). Thus, evidence of five positive integrant and replicative experiments is not sufficient for the skilled artisan to envisage what constitutes a necessary core structure and/or sequence that would exhibit the claimed function of preventing or treating any disease. Therefore, claims 15-27 do not meet the written description requirement.
7. Claims 15-27 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 an infection caused by an intracellular pathogen wherein the intracellular pathogen is dengue virus, coxsackie B4 virus, SARS-CoV-2, influenza virus, and herpes simplex virus comprising administering a CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y; wherein the sequence AG-HGQVDNF-SL (i.e., SEQ ID NO: 1) treats dengue virus infection, the sequence EK-FRDIRGF-LA (SEQ ID NO:2) treats Coxsackie B4 infection, the sequence ATR-FASVYAW-NRK (SEQ ID N0:3) treats SARS-CoV-2 infection, the sequence GL-FGAIA GF-IE (SEQ ID NO:4) treats influenza virus infection, and the sequence VL-FLHLYLF-LT ( SEQ ID NO: 5) treats Herpes simplex virus infection.
However, the specification does not reasonably provide enablement for prevention or treatment of any disease caused by any intracellular pathogen by administering any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, to a subject having the disease. As such, the specification fails to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation'." In re Wriqht, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection." The principle was explicitly affirmed most recently in Auto. Tech. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortriqht, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether
there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessarily needed to make or use the invention based on the disclosure. See In re Wands USPQ 2d 1400 (CAFC 1988). The eight In re Wands factors are applied to claims 15-27 as follows:
The Breadth of the Claims and The Nature of the Invention
Applicants do not provide evidence in the specification that any CD-1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, prevents or treats any disease caused by any intracellular pathogen when administered to a subject having any disease. Thus the scope of claim 15 encompasses a vast array of intracellular pathogens, a vast array of diseases and a vast array of CD1 peptide epitopes. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claim is directed. The claim is extremely broad due to the vast number of possible CD1 peptide-epitopes, intracellular pathogens and diseases.
The State of the Prior Art
Although the state of the art is relatively high with regard to methods of treating a disease by administering peptide-epitopes. In particular the state of the art teaches that vaccine science has extended beyond genomics to proteomics and has come to also encompass ‘immunomics,’ the study of the universe of pathogen-derived or neoplasm-derived peptides that interface with B and T cells of the host immune system (see De Groot et al., Clinical Applications of Immunomics. 2008, 2:39–69, at pg. 39, abstract). De Groot’s review cites additional works which are examples in the literature that ‘a single epitope protects’; for instance Crowe et al. (2006) recently found that immunization with a single Th epitope provided a one-log reduction in influenza viral titers early in infection (see De Groot et al., pg. 41, paragraph 2). A single epitope has also been shown to protect against viral disease in woodchucks (Menne et al. 1997), and multiple single epitopes have protected mice against an array of pathogens (An and Whitton 1997 and Olsen et al. 2000) (see De Groot et al., pg. 41, paragraph 2). A more diverse set of T cell epitopes appear to be critical to immune response to vaccinia (in mice): 49 Class I MHC epitopes were shown to contribute to the large majority of the CD8+ T cell immune response (Moutaftsi et al. 2006). Remarkably, it was found that 49 of these predicted epitopes (derived from more than 175,000 candidates) represented over 90% of the vaccinia-specific CD8 T cell repertoire (see De Groot et al., pg. 41, paragraph 2). De Groot adds that an epitope-based ‘immunome-derived vaccine’ (IDV) for genetically diverse populations of humans will almost certainly require more than that number of epitopes (i.e., 49), particularly if the vaccine is intended to protect against complex bacteria or viruses, or against solid tumors presenting variable antigenic profiles (see De Groot et al., pg. 41, paragraph 2).
Furthermore, Lai et al. teach that issues of immunodominance are an important consideration for any vaccine design strategy, but particularly for peptide vaccines that focus on only a single or a few critical epitopes (see Lai et al., Chem. Rev. 2020, 120, pp. 3210−3229, at pg. 3213, left column, paragraph 2). Lai et al. add that while antibodies that arise in response to infection typically target a number of epitopes on the pathogen, higher numbers of antibodies mature toward some epitopes versus others (see pg. 3213, left column, paragraph 2). A common strategy is to utilize naturally occurring antibodies or TCRs as a template for vaccine design, following the logic that if a particular epitope has already elicited a B- or T-cell response during natural disease, then it is sufficiently immunogenic to allow induction of similar responses by administration of a vaccine (see pg. 3213, left column, paragraph 2). In other cases, epitopes that elicit an immune response most favorable for mitigating the disease may not be the most immunodominant, and thus vaccination with critical epitopes may skew the immune response to yield protective responses (see pg. 3213, left column, paragraph 2). A good example of this is in HIV-1, where the vast majority of antibodies that arise during natural infection target nonconserved or non-neutralizing epitopes (see pg. 3213, left column, paragraph 2).
Lai et al. conclude that like all vaccines, a continual challenge with peptide vaccines stems from the fact that immune responses are still very difficult to predict (see pg. 3222, left column, second paragraph). Thus, the development of optimal immunogens often requires a laborious trial-and-error process of animal immunizations followed by characterization of resulting immune responses (see pg. 3222, left column, second paragraph). Even with this, there can often be species differences, and thus what works in a mouse may not work in a primate (see pg. 3222, left column, second paragraph). There is increasing evidence that the structure of peptide B-cell epitopes can be important for eliciting antibodies of desired function (e.g., neutralizing activity), and thus methods aimed at stabilizing or presenting peptide epitopes in conformationally relevant contexts are likely to improve the success of vaccines that aim to elicit antibody responses (see pg. 3222, left column, second paragraph). For infectious disease, this may be especially important in the context of neutralizing epitopes where function of the epitope is often tied to its three-dimensional structure (see pg. 3222, left column, second paragraph). For Alzheimer’s disease, targeting the appropriate pathologic oligomeric state of Aβ or Tau may prove to be an important factor for next-generation immunotherapies or vaccines (see pg. 3222, left column, second paragraph). For cancer vaccines, much of the current effort is focused on devising new methods to identify new T-cell epitopes that are specific to the tumor; many of the peptide epitopes can be assessed in vitro utilizing peptide–MHC complexes or using HLA-presenting cells and T-cells (see pg. 3222, left column, third paragraph).
Lastly, Tang et al. teach that developing T cell epitope-based vaccines against infection is challenging because epitope discovery remains a challenging and labor-intensive task due to the nature of T cell recognition (see Tang et al., Vaccines. 2025, 13(2) 135, at pg. 2, third paragraph). The vast diversity of the T cell receptor (TCR) repertoire means that specific T cell clones for a given antigen are often present in very low numbers (see pg. 2, third paragraph). Additionally, the affinity of TCR-pMHC interactions is much lower compared to the interactions between antibodies and antigens, making it difficult to detect these scarce populations of interest (see pg. 2, third paragraph). Moreover, antigen processing and presentation generate a wide variety of peptides that must be synthesized or expressed in antigen-presenting cells (APCs) for screening T cell epitopes (see pg. 2, third paragraph). Furthermore, the high degree of TCR cross-reactivity complicates matters, as a single TCR can bind to as many as 1 million different epitopes presented by polymorphic HLA molecules (see pg. 2, third paragraph).
Therefore, the level of predictability in the art is dependent on many factors including a genetically diverse population of humans, unpredictable immune response elicited by the epitope, characterization of immune responses, species differences (i.e., what wors in a mouse may not work in a primate), structure-function of the epitope (for infectious diseases the three-dimensional structure of epitope is often tied to its function), diversity of the T cell receptor (TCR) repertoire and low numbers of specific T cell clones for a given antigen, high degree of TCR cross-reactivity. Additionally, the court has indicated that the more unpredictable an area is the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work. As such, a method of treating a disease, comprising: any CD-1 peptide epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, prevents or treats any disease caused by any intracellular pathogen when administered to a subject having any disease, involves a very high level of unpredictability.
The Level of Skill in the Art
Practitioners in this art (scientist, researchers, medical clinicians, pharmacists, doctors and/or pharmaceutical chemists) would presumably be highly skilled in the art for a method treating a disease comprising a CD-1 peptide epitope as claimed.
The Level of Predictability in the Art
The instant claimed invention is highly unpredictable. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (i.e., a method of treating any disease comprising administering any CD-1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H), then there is a lack of predictability in the art. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
In the instant case, Applicants do not demonstrate that any CD-1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, prevents or treats any disease caused by any intracellular pathogen when administered to a subject having any disease. Rather, Applicants only demonstrate that a handful of sequences, which comprise a CD1 binding motif underlined (i.e., SEQ ID NO: 1 AG-HGQVDNF-SL; SEQ ID NO: 2 EK-FRDIRGF-LA; SEQ ID NO: 3 ATR-FASVYAW-NRK; SEQ ID NO: 4 GL-FGAIA GF-IE; and SEQ ID NO: 5 VL-FLHLYLF-LT), produce an immune response against dengue virus infection, Coxsackie B4 infection, SARS-CoV-2 infection, influenza virus infection and Herpes simplex virus infection, respectively, when administered to mice (see instant specification, Examples 1-5, pp. 18-26). Applicants appear to rely on the assumption that by providing evidence based on the effects of five CD1 peptide-epitopes (i.e., SEQ ID NOs: 1-5) that produce an immunological response against five different infections caused by five different intracellular pathogens in mice would treat any disease in a subject.
However, such an assumption cannot be made because there is no indication that administering any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, to any subject having any disease would prevent or treat any disease caused by any intracellular pathogen. Therefore, it is unpredictable that the claimed method would treat any disease in a subject having the disease.
The Amount of Direction Provided by the Inventor and
The Presence or Absence of Working Examples
The specification does not enable any person skilled in the art to which it pertains (i.e. a method of treating a disease) to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification with regard to the actual treatment of any disease comprising administering any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, to a subject having any disease. Applicants fail to provide the guidance and information required to ascertain whether the claimed method of treating a disease will be effective in the prevention or in the treatment of any disease by administering any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, without resorting to undue experimentation. Applicants' limited disclosure is noted but is not sufficient to justify claiming a method of treating a disease as claimed.
Absent a reasonable a priori expectation of success for using any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y of the claimed invention to obtain a method of treating any disease, one skilled in the art would have to extensively test many CD1 peptide-epitopes to treat many different diseases caused by many intracellular pathogens. Since each prospective embodiment, and indeed future embodiments as the art progresses, would have to be empirically tested, and those which initially failed tested further, an undue amount of experimentation would be required to practice the invention as it is claimed in its current scope, because the specification provides inadequate guidance to do otherwise.
The amount of direction or guidance presented in the specification is limited to treating dengue virus infection, Coxsackie B4 infection, SARS-CoV-2 infection, influenza virus infection and Herpes simplex virus infection (see instant specification, pp. 18-26). Moreover, as noted in “Breadth of the Claims and Nature of the Invention" and “The Level of Predictability in the Art” Sections, the scope of the claim is extensive because it is not obvious that the disclosure of a CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, will prevent or treat any disease. Additionally, the level of predictability in the art of epitope-based vaccination is dependent on many factors, which have not been specified by the instant specification. In the absence of such information, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation.
The Quantity of Experimentation Necessary
In light of the unpredictability surrounding the claimed subject matter, the undue breadth of the claimed invention’s intended use, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. One wishing to practice the presently claimed invention would have to produce additional data and experimentation to determine whether any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, will prevent or treat any disease.
Furthermore, a person of skill in the art would require an undue quantity of experimentation even to select which of the broad array of CD1 peptide-epitopes produces an immune response against any disease caused by any intracellular pathogen. Moreover, a person of skill in the art would also be required to conduct numerous experiments for each intracellular pathogen under different experimental parameters such as characterization of immune responses, species differences (i.e., what wors in a mouse may not work in a primate), structure-function of the epitope (for infectious diseases the three-dimensional structure of epitope is often tied to its function), diversity of the T cell receptor (TCR) repertoire, numbers of specific T cell clones for a given antigen, degree of TCR cross-reactivity, etc., to ensure the efficacy of a method of treating a disease as claimed.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, before the effective filing date of the claimed invention, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
After applying the Wands factors and analysis to claims 15-27, in view of the Applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 15-27 would not be enabled by the written disclosure for prevention or treatment of any disease caused by any intracellular pathogen by administering any CD1 peptide-epitope comprising the sequence X1X2X3X4X5X6X7; wherein said X2, X3, X4, X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, to a subject having the disease.
Therefore, claims 15-27 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art for a method of treating a disease, comprising: administering the CD1 peptide-epitope to a subject having the disease, and administering at least one of an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 epitope-epitope and at least one MHC Class I epitope.
Claim Rejections - 35 USC § 102
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.
8. Claims 15-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US2018/0346887A1 Pub. Date: Dec. 6, 2018 (herein after “Saint-Remy”).
For claims 15 and 18, Saint-Remy discloses a pharmaceutical composition for the prevention or treatment in a mammal, of a condition selected from the group consisting of an infection with an intracellular pathogen, a tumor, an autoimmune disease, an immune response to an allofactor or to allergen exposure, an allograft rejection, and an immune response against a viral vector used for gene therapy or gene vaccination, said pharmaceutical composition comprising a peptide according to claim 17 (see pg. 20, claim 28); thereby corresponding to a method of treating a disease, wherein the disease is caused by an intracellular pathogen and also corresponding to administering the CD1 peptide-epitope to a subject having the disease.
Saint-Remy’s peptide consist of a cell epitope with a [FWHY]-xx-[ILMV]-xx-[FWHY] motif of an antigenic protein (see pg. 20, claim 17), thereby corresponding to wherein said CD1 peptide-epitope includes the sequence X1X2X3X4X5X6X7; said X2, X3, X4,X5, and X6 independently stand for any amino acid; and said X1 and X7 residues are independently F, W, T, H, or Y, as recited in instant claim 15; and also corresponding to wherein X4 is I, V, L, or M as recited in instant claim 18.
Saint-Remy’s method of treating a subject for an infection with an intracellular pathogen comprises administrating a therapeutic amount of a peptide according to claim 17 (see pg. 20, claim 29), thereby corresponding to administering the CD1 peptide-epitope to a subject having the disease; a nucleic acid encoding a peptide according to claim 17; an agent against a condition selected from the group consisting of: an infection with an intracellular pathogen, said agent comprising a peptide according to claim 17 (see pg. 20, claim 29). Saint-Remy’s agent is being interpreted as the at least one MHC Class I epitope recited in instant claim 15; thereby corresponding to administering a second peptide comprising the CD1 peptide-epitope and at least one MHC Class I epitope.
Saint-Remy also discloses that the NKT-cell epitope is derived from an intracellular pathogen, such pathogens can be viruses such as RNA viruses, as examples Herpesviridae, Flaviviridae and Picornaviridae (see pg. 8, para[0122]); thereby corresponding to wherein said disease is a viral disease caused by a virus as recited in instant claim 16, and corresponding to wherein said virus is selected from the group consisting of Flaviviridae, Herpesviridae and Picornaviridae as recited in instant claim 17..
Accordingly, instant claims 15-18 are anticipated by Saint-Remy’s disclosure.
Claim Rejections - 35 USC § 103
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.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
9. Claims 15 and 19-28 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0346887A1 Pub. Date: Dec. 6, 2018 (herein after “Saint-Remy”) for claim 15 above, in view of WO 02/19986 A1 International Pub. Date: March 14 2002 (herein after “Sette”) as evidenced by Oyarzun et al. 2015. Int J Immunogenet, 42: 313-321 (herein after “Oyarzun”) for claims 19-28 herewith.
See Saint-Remy’s discussion above.
Regarding claims 19 and 21-22, Saint-Remy teaches that natural killer T (NKT) cell epitope consists of 7 consecutive amino acids with a [FWHY]-xx-[ILMV]-xx-[FWHY] motif of an antigenic protein (see pg. 20, claim 21). However, Saint-Remy does not expressly teach wherein the CD1 peptide-epitope does not comprise an MHC class II epitope, as recited in instant claim 19.
Sette claims a composition comprising at least one hepatitis B (HBV) peptide, the peptide comprising an isolated, prepared epitope (see pg. 217, claim 1). Sette teaches that an epitope-based vaccine provides the ability to direct and focus an immune response to multiple selected antigens from the same pathogen (see pg. 5, lines 1-2). Sette’s teachings are related to specific epitope pharmaceutical compositions and methods of use in the prevention and treatment of HBV infection (see pg. 6, lines 1-3). Sette adds that the advantage of an epitope-based approach over the use of whole antigens is that there is evidence that the immune response to whole antigens is directed largely toward variable regions of the antigen, allowing for immune escape due to mutations (see pg. 4, lines 21-24). Furthermore, immunosuppressive epitopes that may be present in whole antigens can be avoided with the use of epitope-based vaccines (see pg. 4, lines 21-24).
In order to identify supermotif- or motif-bearing epitopes in a target antigen, a native protein sequence, e.g., a tumor-associated antigen, or sequences from an infectious organism, or a donor tissue for transplantation, is screened using a means for computing, such as an intellectual calculation or a computer, to determine the presence of a supermotif or motif within the sequence (see pg. 35, lines 24-28). The information obtained from the analysis of native peptide can be used directly to evaluate the status of the native peptide or may be utilized subsequently to generate the peptide epitope (see pg. 35, lines 28-30). Sette also displays the identified HBV peptides and analogs that are able to bind HLA supertype groups or allele-specific HLA molecules (see pg. 37, lines 22-24, and Table VII). Therefore, Sette’s identified HBV peptides and analogs that are able to bind to HLA groups or molecules which are used in the preparation of the epitope are being interpreted as not comprising an MHC class II epitope nor a MHC class I epitope. Additionally, Sette’s claim 1 includes a group of prepared epitope sequences which consisting RWMCLRRFII (see pg. 217, claim 1). It is noted that the sequence reads the instantly claimed CD1 peptide-epitope sequence wherein X1 and X7 are independently F, W, T, H, or Y, and wherein X4 is I, V, L, or M. Thereby Sette’s teachings correspond to wherein the CD1 peptide -epitope does not comprise an MHC class II epitope nor an MHC class I epitope as recited in instant claims 19 and 21-22.
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate Sette’s teachings as part of Saint-Remy’s method of treating a subject for an infection with an intracellular pathogen, in order to arrive at the instantly claimed method of treating a disease. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because it was known that epitope-based vaccines provide the ability to direct and focus an immune response to multiple selected antigens from the same pathogen; because it was also known that that the advantage of an epitope-based approach over the use of whole antigens is that there is evidence that the immune response to whole antigens is directed largely toward variable regions of the antigen, allowing for immune escape due to mutations; and because immunosuppressive epitopes that may be present in whole antigens can be avoided with the use of epitope-based vaccines.
One of ordinary skill in the art before the effective filing date of the claimed invention would have had a reasonable expectation of success given that Sette’s prepared epitope consist of a sequence (i.e., RWMCLRRFII) which reads on the instantly claimed CD1 peptide-epitope comprising the X1X2X3X4X5X6X7 sequence wherein X1 and X7 are independently F, W, T, H, or Y, and wherein X4 is I, V, L, or M. Therefore, incorporating Sette’s teachings as part of a Saint-Remy’s method of treating a subject for an infection with an intracellular pathogen would support the instantly claimed method of treating a disease, by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Regarding claims 20 and 23, Sette teaches that the prepared epitope is admixed or joined to an HTL epitope (see pg. 217, claim 5). As evidenced by Oyarzun, CTLs recognize intracellular peptides presented by MHC class I molecules (CTL epitopes) and HTL recognize peptides from the extra-cellular space that are displayed by MHC class II molecules (HTLs epitopes) (see pg. 313, right column, paragraph 1). As such the teachings of Saint-Remy when combined with the teachings of Sette are suggestive of the claim limitations recited in instant claims 20 and 23.
Regarding claims 24-27, Saint-Remy teaches that immunogenic peptides (i.e., peptides comprising the general sequence [FWHY]-xx-[ILMV]-xx[FWHY]) can be identified by methods known by those skilled in the art using algorithms accessible on line (see pg. 9, para[0132]). Said peptides should then be tested in vitro for reactivity with NKT cells (see pg. 9, para[0135]). To this end, CD1d+ APC (antigen presenting cell) are prepared from either an animal or human source (see pg. 9, para[0135]). The cells are then incubated with the peptide of interest and a source of NKT cells (see pg. 9, para[0135]). Activation of the later can be identified by proliferation, production of cytokines such as IFN-gamma and IL-4 and surface markers (see pg. 9, para[0135]). Thus, Saint-Remy’s invention relates to the use of hydrophobic peptides having the capacity to bind to CD1d and thereby recruit and activate NKT cells, coupled to a thiol-oxidoreductase motif (see pg. 2, para[0018]). Such peptides ensure antigen specificity and represent a valuable approach for the treatment of infectious diseases with intracellular pathogens (see pg. 2, para[0018]). Saint-Remy adds that the modified NKT cell epitope can have the same binding affinity for the CD1 d protein as the natural epitope, but can also have a lowered affinity (see pg. 10, para[0145]). In particular embodiments the binding affinity of the modified peptide is no less than 10-fold less than the original peptide, more particularly no less than 5 times less (see pg. 10, para[0145]). Therefore, the teachings of Saint Remy suggest the claim limitations as recited in instant claims 24-27.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 USC 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references discussed above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
10. Claims 15 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 10, 13 and 15 of U.S. Patent No. US 11,193,114 B2 (Pub. No. US 2018/0346887 A1) in view of Lai et al., Chem. Rev. 2020, 120, pp. 3210−3229 (herein after “Lai”), and Comber et al., 2014, Ther Adv Vaccines. 2(3):77-89 (herein after “Comber”).
Regarding instant claims 15 and 18, U.S. Patent No. US 11,193, 114 B2 claims:
An isolated immunogenic peptide consisting of: (1) a natural killer T (NKT) cell epitope having a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] (SEQ ID NO: 23) motif of an antigenic protein; wherein X stands for any amino acid, and wherein said antigenic protein is not surviving (see ‘114, column 53, claim 1).
The isolated immunogenic peptide according to claim 1, wherein the antigenic protein is selected from the group consisting of: a tumor associated antigenic protein, a viral protein, an autoantigen, an allofactor, an allergen, an alloantigen shed by a graft, an antigen of an intracellular pathogen, and an antigen from a viral vector used for gene therapy or gene vaccination (see ‘114, column 53, claim 3).
The isolated immunogenic peptide according to claim 1, wherein the natural killer T (NKT) cell epitope consists of 7 amino acids with a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] (SEQ ID NO: 23) motif of an antigenic protein (see ‘114, column 53, claim 4).
The isolated immunogenic peptide according to claim 1, wherein said NKT cell epitope has a [F or W]-XX-[I, L, M or V]-XX-[F or W] (SEQ ID NO: 13) motif (see ‘114, column 53, claim 5).
13. The isolated immunogenic peptide according to claim 1, wherein said NKT cell epitope is FLRVPCWKI (SEQ ID NO: 38) (see ‘114, column 54, claim 13).
A method of treating a subject for a disease selected from the group consisting of: an infection with an intracellular pathogen, a tumor, an autoimmune disease, an immune response to an allofactor or to allergen exposure, an allograft rejection, and an immune response against a viral vector used for gene therapy or gene vaccination, comprising administrating a therapeutic amount of a nucleic acid encoding the isolated immunogenic peptide according to claim 1 to said subject (see ‘114, column 54, claim 15).
However, U.S. Patent No. US 11,193,114 B2 does not claim administering an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope as recited in instant claim 15.
Lai et al. teach that inactive or attenuated pathogens can stimulate a robust immune response because they contain both B- and T-cell epitopes presented in a conformation that is relevant to the pathogen (see pg. 3211, left column, paragraph 3).
An ordinary skilled artisan would have been motivated with reasonable expectation of success to administer an inactive or attenuated pathogen after administering the isolated immunogenic peptide consisting of a natural killer T (NKT) cell epitope having a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] as part of a method of treating a subject for a disease consisting of an infection with an intracellular pathogen, because as taught by Lai et al. inactive or attenuated pathogens can stimulate a robust immune response since they contain both B and T cell epitopes.
However, U.S. Patent No. US 11,193,114 B2 does not claim a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 peptide-epitope and at least one MHC Class I epitope, as recited in instant claim 15.
Comber teaches MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines (see pg. 77, Title). Comber adds that Major Histocompatibility complex Class I (MHCI) molecules are present on the surface of all nucleated cells and display a large array of peptide epitopes for surveillance by the CD8+ T cell repertoire (see pg. 77, left column, introduction). Comber also teaches that peptide based vaccines have significant advantages because these vaccines are flexible in their design and can accommodate many peptide epitopes in a single dose (see pg. 84, right column, paragraph 1). This allows for multiple MHC-I epitopes to be included to initiate a T cell response (see pg. 84, right column, paragraph 1). This is an important feature because not all individuals share the same MHC alleles; peptides that bind to single alleles (i.e. HLA-A2 or HLA-A24) and peptides that bind to multiple alleles (i.e. HLA-A2 and HLA-A24) can be included in the same formulation (see pg. 84, right column, paragraph 1). Thus, a vaccine derived from naturally processed peptides can be given to individuals with a wide diversity in their MHC alleles and still be effective (see pg. 84, right column, paragraph 1). As such, an ordinary skilled artisan would have been motivated with reasonable expectation of success to include an MHC class I epitope as part of the method of treating a subject for a disease consisting of an infection with an intracellular pathogen where an isolated immunogenic peptide consisting of a natural killer T (NKT) cell epitope having a [F, W, H or Y]-XX-[I, L, M or V]-XX-[F, W, H or Y] is administered, in order to arrive at the claimed invention.
11. Claims 15, 18, 24-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. US 11,236,127 B2 (Pub. No. US 2019/0302375 A1) in view of WO 2008/133759 A2 International Publication Date: Nov. 6, 2008 (herein after “Chisari”), Lai et al., Chem. Rev. 2020, 120, pp. 3210−3229 (herein after “Lai”), and Comber et al., 2014, Ther Adv Vaccines. 2(3):77-89 (herein after “Comber”).
Regarding instant claims 15, 18 and 24-26, U.S. Patent No. US 11,236,127 B2 claims:
A method of treating in a mammalian subject an infection, the method comprising
identifying a peptide or polypeptide from an agent causing the infection in the mammalian subject, wherein the peptide or polypeptide does not activate NKT cells when the peptide or polypeptide is incubated with a cell line expressing CD1d and NKT cells; introducing at least one, or at least one additional, CD1d binding motif comprising [FWHY]-X2X3-[ILMV]-X5X6-[FWHY] into the said peptide or polypeptide so as to generate a modified peptide or polypeptide; selecting a modified peptide or polypeptide that activates NKT cells when the peptide or polypeptide is incubated with a cell line expressing CD1d and NKT cells; and administering the modified peptide or polypeptide that activates NKT cells to the mammalian subject, wherein identifying a peptide or polypeptide that does not activate NKT cells comprises determining the capacity of the peptide or polypeptide to bind to CD1d, and, for peptides or polypeptides having the capacity to bind to CD1d, determining the ability to activate NKT cells by incubation of the modified peptide or polypeptide with cells expressing CD1d, followed by addition of a population of NKT cells, and detecting NKT cell activation (see ‘127, column 31, claim 1).
A method of activating NKT cells in a mammal, the method comprising identifying a peptide or polypeptide that does not activate NKT cells when the peptide or polypeptide is incubated with a cell line expressing CD1d and NKT cells; introducing at least one, or at least one additional, CD1d binding motif comprising [FWHY]-X2X3-[ILMV]-X5X6-[FWHY] into the peptide or polypeptide so as to generate a modified peptide or polypeptide; selecting a modified peptide or polypeptide that activates NKT cells; and administering the said modified peptide or polypeptide that activates NKT cells to the mammal, wherein the NKT cells are Type I NKT cells, wherein identifying a peptide or polypeptide that does not activate NKT cells comprises determining the capacity of the peptide or polypeptide to bind to CD1d, and, for peptides or polypeptides having the capacity to bind to CD1d, determining the ability to activate NKT cells by incubation of the modified peptide or polypeptide with cells expressing CD1d, followed by addition of a population of NKT cells, and detecting NKT cell activation (see ‘127, columns 31-32, claim 2).
The method of claim 1, further comprising selecting a modified peptide or polypeptide that activates cytolytic activity and cytokine production by CD4+ NKT cells in the mammalian subject (see ‘127, column 32, claim 3)..
The method of claim 2, further comprising selecting a modified peptide or polypeptide that activates a cytolytic activity and cytokine production by CD4+ NKT cells in the mammalian subject (see ‘127, column 32, claim 4).
The method of claim 1, wherein selecting a modified peptide or polypeptide that activates NKT cells comprises determining the capacity of the peptide or polypeptide to bind to CD1d, and, for peptides or polypeptides having the capacity to bind to CD1d, determining the ability to activate NKT cells by incubation of the modified peptide or polypeptide with cells expressing CD1d, followed by addition of a population of NKT cells, and detecting NKT cell activation (see claim ‘127, column 32, claim 5).
The method of claim 2, wherein selecting a modified peptide or polypeptide that activates NKT cells comprises determining the capacity of the peptide or polypeptide to bind to CD1d, and, for peptides or polypeptides having the capacity to bind to CD1d, determining the ability to activate NKT cells by incubation of the modified peptide or polypeptide with cells expressing CD1d, followed by addition of a population of NKT cells, and detecting NKT cell activation (see ‘127, column 33, claim 6).
However, U.S. Patent No. US 11,236,127 B2 does not claim wherein the disease is caused by an intracellular pathogen, nor administering an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope, nor wherein a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 peptide-epitope and at least one MHC Class I epitope, as recited in instant claim 15.
Chisari’s invention is drawn to antiviral peptides and methods of using these peptides to prevent or inhibit infections by a human immunodeficiency virus or a virus from the Flaviviridae family (see pg. 1, abstract). In particular Chisari claims a method for preventing or treating a viral infection in a mammal comprising administering to the mammal an effective amount of a peptide of claim 1 (see pg. 175, claim 46). Chisari’s invention involves an amphipathic alpha-helical peptide derived from the membrane anchor domain of the Hepatitis C virus (HCV) NS5A protein is virocidal for HCV, i.e. it is capable of inactivating HCV, at nanomolar concentrations in vitro (see pg. 2, second paragraph). The peptide prevents de novo HCV infection and suppresses ongoing infection by inactivating both extracellular and intracellular infectious particles (see pg. 2, second paragraph). In addition to HCV, the peptide inhibits infection by selected flaviviruses, paramyxoviruses, and HIV (see pg. 2, second paragraph). The peptide is also nontoxic in vitro and in vivo at doses at least 100-fold higher than required for antiviral activity (see pg. 2, second paragraph). As such, an ordinary skilled artisan would have been motivated with reasonable expectation of success to combine claims 1-6 of U.S. Patent No. US 11,236,127 B2 with the teachings of Chisari in order to arrive at the claimed method of treating a disease, wherein the disease is caused by an intracellular pathogen, as recited in instant claim 15.
Also, Lai et al. teach that inactive or attenuated pathogens can stimulate a robust immune response because they contain both B- and T-cell epitopes presented in a conformation that is relevant to the pathogen (see pg. 3211, left column, paragraph 3). Therefore, an ordinary skilled artisan would have been motivated with reasonable expectation of success to administer an inactive or attenuated pathogen as part of a method of treating in a mammalian subject an infection as taught by U.S. Patent No. US 11,236,127 B2; because inactive or attenuated pathogens can stimulate a robust immune response since they contain both B and T cell epitopes, as taught by Lai.
Moreover, an ordinary skilled artisan would also have been motivated with reasonable expectation of success to include an MHC class I epitope as part of a method of treating in a mammalian subject an infection as taught by U.S. Patent No. US 11,236,127 B2, because Comber teaches that Major Histocompatibility complex Class I (MHCI) molecules are present on the surface of all nucleated cells and display a large array of peptide epitopes for surveillance by the CD8+ T cell repertoire (see pg. 77, left column, introduction). Comber also teaches that peptide based vaccines have significant advantages because these vaccines are flexible in their design and can accommodate many peptide epitopes in a single dose (see pg. 84, right column, paragraph 1). Thus, a vaccine derived from naturally processed peptides can be given to individuals with a wide diversity in their MHC alleles and still be effective (see pg. 84, right column, paragraph 1). Accordingly, instant claims 15, 18, 24-26 are rejected on the ground of nonstatutory double patenting.
12. Claims 15 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 5-6 of U.S. Patent No. 10,023,847 B2 (Pub. No. US 2013/0259885 A1) in view of WO 2008/133759 A2 International Publication Date: Nov. 6, 2008 (herein after “Chisari”), Lai et al., Chem. Rev. 2020, 120, pp. 3210−3229 (herein after “Lai”), and Comber et al., 2014, Ther Adv Vaccines. 2(3):77-89 (herein after “Comber”).
Regarding instant claims 15 and 18, U.S. Patent No. 10,023,847 B2 claims:
A method for preparing a peptide capable of eliciting NKT cell activation, said method comprising the steps of: (1) identifying within an antigenic protein a NKT cell epitope sequence comprising a [FWHY]-xx-[ILMV]-xx-[FWHY] motif, wherein x is any amino acid, wherein [FWHY] is an amino acid selected from Phe, Trp, His, and Tyr, and wherein [ILMV] is an amino acid selected from Ile, Leu, Met, and Val, (2) testing a peptide with a NKT cell epitope sequence identified in step (1) in vitro for activation of NKT cells when said peptide is presented by CD1d, and (3) providing a peptide comprising: a NKT cell epitope tested in step (2) and having confirmed activation of NKT cells, linked to a thioreductase [CST]-xx-C or C-xx-[CST] motif, wherein x is any amino acid, and wherein [CST] is an amino acid selected from Cys, Ser, and Thr, such that said thioreductase motif and said NKT cell epitope sequence are either immediately adjacent to each other or separated by a linker of at most 7 amino acids in length (see columns 35-37, claim 1).
The method according to claim 1, wherein said antigenic protein is selected from the group consisting of an autoantigen, an allofactor, an allergen, a tumor associated antigen, an alloantigen shed by a graft, an antigen from a viral vector used for gene therapy or gene vaccination, and an intracellular pathogen associated antigen (see column 37, claim 2).
The method according to claim 1, comprising in step (1) identifying within an antigenic protein a NKT cell epitope sequence comprising a [FW]-xx-[ILMV]-xx-[FW] motif, wherein [FW] is Phe or Trp (see column 37, claim 5).
The method according to claim 1, comprising in step (1) identifying within an antigenic protein a NKT cell epitope sequence comprising a [FW]-xx-[ILM]-xx-[FW] motif, wherein [ILM] is an amino acid selected from Ile, Leu, and Met (see column 37, claim 6).
However, U.S. Patent No. 10,023,847 B2 does not claim a method of treating a disease, wherein the disease is caused by an intracellular pathogen, nor administering the CD1 peptide-epitope to a subject having the disease, nor administering at least one of an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 epitope-epitope and at least one MHC Class I epitope, as recited in instant claim 15.
Chisari’s invention is drawn to antiviral peptides and methods of using these peptides to prevent or inhibit infections by a human immunodeficiency virus or a virus from the Flaviviridae family (see pg. 1, abstract). In particular Chisari claims a method for preventing or treating a viral infection in a mammal comprising administering to the mammal an effective amount of a peptide of claim 1 (see pg. 175, claim 46). Chisari’s invention involves an amphipathic alpha-helical peptide derived from the membrane anchor domain of the Hepatitis C virus (HCV) NS5A protein is virocidal for HCV, i.e. it is capable of inactivating HCV, at nanomolar concentrations in vitro (see pg. 2, second paragraph). The peptide prevents de novo HCV infection and suppresses ongoing infection by inactivating both extracellular and intracellular infectious particles (see pg. 2, second paragraph). In addition to HCV, the peptide inhibits infection by selected flaviviruses, paramyxoviruses, and HIV (see pg. 2, second paragraph). The peptide is also nontoxic in vitro and in vivo at doses at least 100-fold higher than required for antiviral activity (see pg. 2, second paragraph). As such, an ordinary skilled artisan would have been motivated with reasonable expectation of success to combine claims 1-2 and 5-6 of U.S. Patent No. 10,023,847 B2 with the teachings of Chisari in order to arrive at the claimed method of treating a disease, wherein the disease is caused by an intracellular pathogen, as recited in instant claim 15.
Also, Lai et al. teach that inactive or attenuated pathogens can stimulate a robust immune response because they contain both B- and T-cell epitopes presented in a conformation that is relevant to the pathogen (see pg. 3211, left column, paragraph 3). Therefore, an ordinary skilled artisan would have been motivated with reasonable expectation of success to administer an inactive or attenuated pathogen as part of a method of treating in a mammalian subject an infection as taught by U.S. Patent No. 10,023,847 B2; because inactive or attenuated pathogens can stimulate a robust immune response since they contain both B and T cell epitopes, as taught by Lai.
Moreover, an ordinary skilled artisan would also have been motivated with reasonable expectation of success to include an MHC class I epitope as part of a method of treating in a mammalian subject an infection as taught by U.S. Patent No. 10,023,847 B2, because Comber teaches that Major Histocompatibility complex Class I (MHCI) molecules are present on the surface of all nucleated cells and display a large array of peptide epitopes for surveillance by the CD8+ T cell repertoire (see pg. 77, left column, introduction). Comber also teaches that peptide based vaccines have significant advantages because these vaccines are flexible in their design and can accommodate many peptide epitopes in a single dose (see pg. 84, right column, paragraph 1). Thus, a vaccine derived from naturally processed peptides can be given to individuals with a wide diversity in their MHC alleles and still be effective (see pg. 84, right column, paragraph 1). Accordingly, instant claims 15 and 18 are rejected on the ground of nonstatutory double patenting.
13. Claims 15 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-4 of U.S. Patent No. 11,091,512 B2 (Pub. No. US 2018/0009843 A1) in view of WO 2008/133759 A2 International Publication Date: Nov. 6, 2008 (herein after “Chisari”), Lai et al., Chem. Rev. 2020, 120, pp. 3210−3229 (herein after “Lai”), and Comber et al., 2014, Ther Adv Vaccines. 2(3):77-89 (herein after “Comber”).
Regarding instant claims 15, 18 and 24-26, U.S. Patent No. 11,091,512 B2 claims:
A method for the production of an engineered peptide or polypeptide, comprising the steps of
providing a CD1d-binding peptide or polypeptide selected from the group consisting of an allofactor peptide or polypeptide, a viral vector peptide or polypeptide, a peptide or polypeptide of a genetically-modified organism, and a peptide or polypeptide vaccine for an allergen, which comprises one or more motifs consisting of [F/W/T/H/Y]-X2X3-[I/L/M/V]-X5X6-[F/W/T/H/Y] and binds to CD1d; and substituting the [F/W/T/H/Y] amino acids at positions P1 and P7 of the motif by an amino acid different from [F/W/T/H/Y] to provide an engineered peptide or polypeptide, wherein the binding to CD1d by the engineered peptide or polypeptide is reduced as compared with the CD1d-binding peptide, and wherein the method further comprises the step of measuring if the engineered peptide or polypeptide has a reduced capacity to activate NKT cells as compared with the CD1d-binding peptide or polypeptide (see column 71, claim 2).
The method of claim 2, further comprising measuring the binding of the CD1d-binding peptide or polypeptide to CD1d, or the capacity of the CD1d-binding peptide or polypeptide to activate NKT cells (see column 72, claim 3).
The method of claim 3, further comprising the step of measuring if the engineered peptide or polypeptide has a reduced capacity to bind CD1d as compared with the CD1d-binding peptide or polypeptide (see column 72, claim 4).
However, U.S. Patent No. 11,091,512 B2 does not claim a method of treating a disease, wherein the disease is caused by an intracellular pathogen, nor administering the CD1 peptide-epitope to a subject having the disease, nor administering at least one of an inactivated form of the intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on a protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, said second peptide comprises the CD1 epitope-epitope and at least one MHC Class I epitope, as recited in instant claim 15.
Chisari’s invention is drawn to antiviral peptides and methods of using these peptides to prevent or inhibit infections by a human immunodeficiency virus or a virus from the Flaviviridae family (see pg. 1, abstract). In particular Chisari claims a method for preventing or treating a viral infection in a mammal comprising administering to the mammal an effective amount of a peptide of claim 1 (see pg. 175, claim 46). Chisari’s invention involves an amphipathic alpha-helical peptide derived from the membrane anchor domain of the Hepatitis C virus (HCV) NS5A protein is virocidal for HCV, i.e. it is capable of inactivating HCV, at nanomolar concentrations in vitro (see pg. 2, second paragraph). The peptide prevents de novo HCV infection and suppresses ongoing infection by inactivating both extracellular and intracellular infectious particles (see pg. 2, second paragraph). In addition to HCV, the peptide inhibits infection by selected flaviviruses, paramyxoviruses, and HIV (see pg. 2, second paragraph). The peptide is also nontoxic in vitro and in vivo at doses at least 100-fold higher than required for antiviral activity (see pg. 2, second paragraph). As such, an ordinary skilled artisan would have been motivated with reasonable expectation of success to combine claims 2-4 of U.S. Patent No. 11,091,512 B2 with the teachings of Chisari in order to arrive at the claimed method of treating a disease, wherein the disease is caused by an intracellular pathogen, as recited in instant claim 15.
Also, Lai et al. teach that inactive or attenuated pathogens can stimulate a robust immune response because they contain both B- and T-cell epitopes presented in a conformation that is relevant to the pathogen (see pg. 3211, left column, paragraph 3). Therefore, an ordinary skilled artisan would have been motivated with reasonable expectation of success to administer an inactive or attenuated pathogen as part of a method of treating in a mammalian subject an infection as taught by U.S. Patent No. No. 11,091,512 B2; because inactive or attenuated pathogens can stimulate a robust immune response since they contain both B and T cell epitopes, as taught by Lai.
Moreover, an ordinary skilled artisan would also have been motivated with reasonable expectation of success to include an MHC class I epitope as part of a method of treating in a mammalian subject an infection as taught by U.S. Patent No. 11,091,512 B2, because Comber teaches that Major Histocompatibility complex Class I (MHCI) molecules are present on the surface of all nucleated cells and display a large array of peptide epitopes for surveillance by the CD8+ T cell repertoire (see pg. 77, left column, introduction). Comber also teaches that peptide based vaccines have significant advantages because these vaccines are flexible in their design and can accommodate many peptide epitopes in a single dose (see pg. 84, right column, paragraph 1). Thus, a vaccine derived from naturally processed peptides can be given to individuals with a wide diversity in their MHC alleles and still be effective (see pg. 84, right column, paragraph 1). Accordingly, instant claims 15 and 18 are rejected on the ground of nonstatutory double patenting.
Conclusion
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654