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Claims 28-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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.
The amendment filed on 06/23/2026 cancelled claim 21, and amended claims 15 and 22.
Information Disclosure Statement
The IDSs filed on 06/10/2026 has 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.
Non-Compliant Amendment
Claim 24 has been amended to depend from claim 15. However, Applicant has failed to show the amendments by underlining the added text. See MPEP 714, 37 C.F.R. 1.121(c). See also claim 24, filed on 04/03/2023, and claim 24 filed on 06/23/2026, respectively reproduced below for convenience.
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Appropriate correction is required in response to this office action.
Maintained Objections
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.
Response to Arguments
1. Applicant's arguments filed 06/23/2026, with respect to the claim objections, have been fully considered but they are not persuasive. The objections to claims 22 and 23 have been maintained.
2. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(b), have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection to claims 15-27 has been withdrawn.
3. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(b) (i.e., lack of antecedent basis), have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection to claims 15-27 has been withdrawn.
4. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(b) (i.e., claim dependence upon a cancelled claim), have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection to claims 24-27 has been withdrawn.
5. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(b) (i.e., second peptide ambiguity), have been fully considered and are persuasive. The 35 U.S.C. 112(b) rejection to claims 15-27 has been withdrawn.
6. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(d) (i.e., improper dependent form), have been fully considered and are persuasive. The 35 U.S.C. 112(d) rejection to claims 24-27 has been withdrawn.
7. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(a) (i.e., written description), have been fully considered but are not persuasive. The 35 U.S.C. 112(a) rejection to claims 15-16, 18-20, 22-27 has been maintained.
8. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 112(a) (i.e., enablement), have been fully considered but are not persuasive. The 35 U.S.C. 112(a) rejection to claims 15-20 and 22-27 has been maintained.
9. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 102(a)(1) rejection, have been fully considered and are persuasive. The 35 U.S.C. 102(a)(1) rejection to claims 15-18 has been withdrawn.
10. Applicant's arguments filed 06/23/2026, with respect to the 35 U.S.C. 103 rejection, have been fully considered but and not are persuasive. The 35 U.S.C. 103 rejection to claims 15-20 and 22-27 has been maintained.
11. Applicant's arguments filed 06/23/2026, with respect to the NSDP rejections, have been fully considered and are persuasive. The NSDP rejections have been withdrawn.
New Rejections in light of Amendment
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 15-20, and 22-27 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 has been amended to recite: “and wherein the CD1 peptide-epitope does not comprise an MHC class I epitope;” at line 8. Additionally, lines 13-15 have also been amended to recite: “a second peptide based on said 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 further epitope, an MHC Class I epitope.”
Therefore, claim 15 is internally inconsistent because line 8 recites that the CD1 peptide-epitope does not comprise an MHC class I epitope; while lines 13-15 recite that the second peptide comprises the CD1 peptide-epitope and at least one further epitope, an MHC Class I epitope. Thereby, the second peptide comprising at least one further epitope, wherein the further one or more epitope(s) is being interpreted as an MHC Class I epitope, contradicts the previous statement where it is expressly recited that the CD1 peptide-epitope does not comprise an MHC class I epitope. Thus, the claim is indefinite because the CD1 peptide-epitope comprised by the second peptide cannot be the same as the CD1 peptide-epitope that 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; and does not comprise an MHC class I epitope.
As such, claim 15, and dependent claims 16-20 and 23-27 are indefinite because it is not clear whether the claimed invention comprises an MHC class I epitope or not.
2. Claim 23 is 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 23 is directly dependent on a cancelled claim (i.e., claim 21), therefore the claim is indefinite because it fails to further limit the base claim (i.e., claim 21).
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.
3. Claim 20 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 20 depends upon claim 15, which recites “…administering the CD1 peptide-epitope to a subject having the disease; and administering at least one of: an activated form of said intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on said 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 further epitope, an MHC Class I epitope.”
Claim 20 fails to further limit the claim limitation of parent claim 15, because administering “a second peptide based on said 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 further epitope, an MHC Class I epitope” is one of the treatment alternatives comprised the claimed method of treating a disease. Thus, administering the CD1 peptide-epitope to a subject having the disease and a second peptide […] wherein said second peptide further comprises at least one MHC Class II epitope, fails to further limit parent claim 15, because the second peptide is an alternative and not a required limitation for the claimed method of treating a disease.
Applicants may cancel the claim; amend parent claim 15 to remove alternative language (i.e., “or”) thus making said second peptide a required limitation; or 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.
4. Claims 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 23 is drawn to the method according to claim 21, thus the claim is dependent upon claim 21. However, claim 21 was cancelled in the amendment filed on 06/23/2026. In order to advance prosecution, the Examiner is interpreting claim 23 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. In order to advance prosecution, claim 23 is interpreted as dependent upon claim 20.
5. Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As previously mentioned, claim 23 is being interpreted as depending upon claim 20; and claim 20 depends upon claim 15 which recites “…administering the CD1 peptide-epitope to a subject having the disease; and administering at least one of: an activated form of said intracellular pathogen to the subject after administering the CD1 peptide-epitope; or a second peptide based on said 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 further epitope, an MHC Class I epitope.”
Claim 23 fails to further limit the claim limitation of parent claim 15, because administering “a second peptide based on said 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 further epitope, an MHC Class I epitope” is one of the treatment alternatives comprised the claimed method of treating a disease. Thus, administering the CD1 peptide-epitope to a subject having the disease and a second peptide […] wherein said second peptide further comprises at least one MHC Class II epitope, fails to further limit parent claim 15, because the second peptide is an alternative and not a required limitation for the claimed method of treating a disease.
Applicants may cancel the claim; amend parent claim 15 to remove alternative language (i.e., “or”) thus making said second peptide a required limitation; or 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. Claim 15 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
In the instant case, claim 15 recites administering “a second peptide based on said 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 further epitope, an MHC Class I epitope.”
Applicants stated in their remarks that support for the amendment to claim 15, can be found on pg. 14, lines 1-2 (see Remarks, filed 06/23/2026, pg. 8 of 12, last paragraph). However, the evidence provided by Applicants does not support that the amended subject matter of claim 15 was previously presented; as there is no mention of a second peptide comprising the CD1 peptide-epitope and at least one further epitope, an MHC Class I epitope. The phrase “one further epitope” is being interpreted as an additional epitope, and that additional epitope is an MHC Class I epitope.
The instant specification recites that the “second peptide which comprises at least one second epitope which is different from the CD1 peptide-epitope” (see instant specification, pg. 14, lines 1-2). This statement does not support the amendment because the specification is silent about the difference between the CD1 peptide-epitope and the second epitope. Thereby, the instantly claimed method of treating a disease, comprising a second peptide wherein the second peptide comprises the CD1 peptide-epitope and at least one further epitope, an MHC Class I epitope, has not been adequately supported.
Maintained/Modified Rejections in light of Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
7. Claims 15-16, 18-20 and 22-27 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. Please note that claim 17 is not rejected, because the claim recites taxonomic details of possible viral diseases to be treated by the claimed method.
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 said 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;
and wherein the CD1 peptide-epitope does not comprise an MHC class I epitope;
administering the CD1 peptide-epitope to a subject having the disease; and
administering at least one of:
an inactivated form of said intracellular pathogen to the subject after administering the CD1
peptide-epitope; or
a second peptide based on said 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 further epitope, an 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, 18-20 and 22-27 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, 15-16, 18-20 and 22-27 do not meet the written description requirement.
8. Claims 15-20 and 22-27 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; 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; does not reasonably provide enablement for the prevention of any disease caused by any intracellular pathogen by administering the 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 15-20 and 22-27 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 15-20 and 22-27, 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 15-20 and 22-27 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 15-20 and 22-27 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 § 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 15-19, 22 and 24-27 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0346887A1 Pub. Date: Dec. 6, 2018 (herein after “Saint-Remy”), 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”).
Regarding claim 15, Saint-Remy teaches 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 constituting a method of treating a disease, wherein the disease is caused by an intracellular pathogen as recited in instant claim 15.
Saint-Remy’s isolated immunogenic peptide consist of a natural killer T cell epitope with a [FWHY]-xx-[ILMV]-xx-[FWHY] motif of an antigenic protein (see pg. 20, claim 17), thereby constituting 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.
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); 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). Therefore, Saint-Remy’s agent is being interpreted as administering the at least one of: an inactivated form of said intracellular pathogen to the subject after administering the CD1 peptide-epitope. Thereby constituting wherein administering the CD1 peptide-epitope to a subject having the disease; and administering an inactivated form of said intracellular pathogen to the subject after administering the CD1 peptide-epitope, as recited in instant claim 15. However, Saint-Remy does not expressly teach wherein the CD1 peptide-epitope does not comprise an MHC class I epitope, as recited in instant claim 15.
Sette’s invention pertains to the development of epitope-based vaccines directed towards HBV (see front pg., abstract). 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 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 an 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 constitute to wherein the CD1 peptide -epitope does not comprise an MHC class II epitope nor an MHC class I epitope as recited in instant claim 15.
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 16-17, 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.
Regarding claim 18, Saint-Remy’s isolated immunogenic peptide consist of a natural killer T cell epitope with a [FWHY]-xx-[ILMV]-xx-[FWHY] motif of an antigenic protein (see pg. 20, claim 17), also constituting wherein X4 is I, V, L, or M as recited in instant claim 18.
Regarding claims 19 and 22, and as previously mentioned above, 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 constitute to wherein the CD1 peptide -epitope does not comprise an MHC class II epitope.
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 online (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.
Response to Arguments
Applicant's arguments filed 06/23/2026 have been fully considered but they are not persuasive.
In response to Applicant’s arguments that claim 15 depends from claim 20, and that the objections should be withdrawn (see Remarks, filed 6/23/2026, pg. 6 of 12). These arguments have been fully considered but are not persuasive because all claims depend from parent claim 15.
In response to Applicant’s arguments pertaining the 35 U.S.C 112(a), i.e., failing to comply with the written description requirement, (see Remarks, filed 06/23/2026, pg. 8 of 12). These arguments have been fully considered but are not persuasive for the following reasons:
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 applicant was in possession of the claimed genus.
As discussed in the rejection above, the scope of the instantly claimed method encompasses treating any disease, comprising administering to a subject having any disease, a fragment of a protein expressed by any intracellular pathogen (i.e., CD1 peptide-epitope), and administering at least one of: an inactivated form of said intracellular pathogen or a second peptide based on said protein of said intracellular pathogen to the subject after administering the CD1 peptide-epitope.
Applicants contend that the instant specification already provides a diverse set of peptides from various different origins, thus providing a broad set of examples (see Remarks, filed 06/23/2026, pg. 9 of 12). However, evidence of five positive integrant and replicative experiments is not sufficient for the skilled artisan to envisage the broad genus of diseases (i.e., any disease) treatable by the claimed method. Accordingly, the 35 U.S.C 112(a) (i.e., written description) rejection to claims 15-16, 18-20, 22-27 is maintained.
In response to Applicant’s arguments pertaining the 35 U.S.C 112(a), i.e., lack of enablement for preventing any disease, (see Remarks, filed 06/23/2026, pg. 9 of 12). These arguments have been fully considered but are not persuasive.
Contrary to Applicant’s arguments, the specification fails to adequately 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 the claims, because there is no evidence that providing a CD1 peptide-epitope as claimed prevents (i.e., as in 100% prevention) any disease. The specification only teaches five examples (i.e., Dengue virus infection, Coxsackie b4 infection, SARS-CoV-2 infection, Influenza virus infection, and Herpes simplex virus infection) wherein after administering the claimed CD1 peptide-epitope the following conclusions were reached:
For Dengue Virus Infection: pre-immunization with a CD1-restricted peptide not only increases the overall immune response towards NS5 but also reduces the differences generally observed when comparing mice of different strains (see instant specification, pg. 20, lines 14-17).
For Coxsackie b4 infection: It is therefore concluded that pre-immunization with peptide of SEQ ID NO:2 reduces the degree of acute acini inflammation due to B4-V infection and, more importantly, prevents the passage into a chronic irreversible stage of pancreatitis (see instant specification, pg. 21, lines 27-30).
For SARS-CoV-2 infection: pretreating mice with a peptide encompassing a CD1-compatible motif increases the immune response towards S protein, alters its characteristics towards increased cytotoxicity and Th1-driven response, and maintains this immune response over time (see instant specification, pg. 23, lines 17-21).
For Influenza virus infection: pre-immunization with a peptide activating NKT cells alters the quality of the immune response obtained after administration of hemagglutinin towards a Th1-driven response and cytotoxicity (see instant specification, pg. 25, lines 10-13).
For Herpes virus infection: that immunization with a peptide containing a CD1-binding motif is sufficient as to shift the response towards acquisition of cytotoxicity properties helpful for the control of HSV infection (see instant specification, pg. 26, lines 34-37).
Thus, an increase in the immune response towards any of the previously mentioned infections, or the improvement of any of the previously mentioned viral infections after administering a CD1 peptide-epitope that 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; and wherein the CD1 peptide-epitope does not comprise an MHC class I epitope, does not translate to prevention of any disease. Accordingly, the 35 U.S.C 112(a) (i.e., enablement) rejection to claims 15-20 and 22-27 is maintained.
In response to Applicant’s arguments pertaining the 35 U.S.C 103 rejection (see Remarks, filed 06/23/2026, pg. 10-11). These arguments have been fully considered but they are not persuasive.
In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., CD1-focused vaccination synergizes with a subsequent more classical vaccination scheme not necessarily focused on CD1/NKT and cytotoxic response) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, the combined effect greater than the sum of their separate effects: of aCD1-peptide epitope as claimed and a more classical vaccination scheme in the treatment of any disease is not encompassed by the claims at issue. Thus, Applicant’s arguments are irrelevant and not persuasive.
Applicant attests that the combination of cited references does not provide any incentive to perform a two-step immunization as currently claimed because the combination fails to teach or suggest a first step comprising administration of a CD1 peptide-epitope not comprising an MHC class I epitope; and because the cited art also fails to suggest a second step comprising administration of a second peptide comprising the CD1 peptide-epitope and at least one further epitope, an MHC Class I epitope (see Remarks, filed 06/23/2026, pg. 11 of 12, second to last paragraph). These arguments have been fully considered but are not persuasive.
In response to Applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, the claims are drawn to a method of treating a disease. The key distinction between treatment and immunization is that treatment of a disease refers to actions taken to manage, reduce or relieve an existing disease or condition; while immunization stimulates the immune system to produce antibodies against a disease. Furthermore, the administration of a second peptide comprising the CD1 peptide-epitope and at least one further epitope, an MHC Class I epitope is an alternative to the required administration of the claimed CD1 peptide-epitope to the subject having the disease. Thus, contrary to Applicant’s argument, Saint-Remmy’s teachings not only read on the claimed CD1 peptide-epitope, but also on the administration of an inactivated form of the intracellular pathogen. Thus, an ordinary skilled artisan would have been motivated to combine the cited prior art in order to arrive at the claimed invention, because Sette’s teachings pertain to epitope-based vaccines which read on the instantly claimed CD1 peptide-epitope and do not comprise an MHC class I or class II epitope.
Accordingly, the 35 U.S.C 103 rejection of claims 15-19, 22 and 24-27 has been maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CLAUDIA E ESPINOSA whose telephone number is (703)756-4550. The examiner can normally be reached Monday-Friday 9:30-5:30 EST.
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
