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 .
Claim Status
The amended claim set filed on 1 May 2026 is acknowledged. Claims 1-24 are currently pending. Of those, claims 3 and 20-21 are amended. There are no new claims and no claims are cancelled. Claims 23-24 are withdrawn. Claims 1-22 will be examined on the merits herein.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-22) in the reply filed on 1 May 2026 is acknowledged. Claims 23-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1 May 2026.
Priority
The instant application is a 371 of application PCT/EP2022/052154 (filed 29 January 2022) and claims priority to foreign application EP 21154244.4 (filed 29 January 2021). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, the disclosure of the foreign priority application does not provide support for “a polyprotein, a DNA encoding for the polyprotein and/or an RNA encoding for the polyprotein, wherein the polyprotein comprises… at least two self-protein segments derived from a second self-protein of the host” as is recited in claim 1 (emphasis added). Therefore, the effective filing date of claims 1-22 is 29 January 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 26 July 2023, 11 September 2023, 5 August 2025, 24 September 2025, and 22 April 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, each information disclosure statement is being considered by the examiner.
Claim Objections
Claims 6, 10, 20, and 22 are objected to because of the following informalities:
In claim 6, line 2, there “third, self-protein” should read “third self-protein”;
In claim 10, line 2, the phrase “is derived from an optionally canine…” is grammatically incorrect;
In claim 20, line 2, the phrase “comprising a including human” is grammatically incorrect; and
In claim 22, line 3, “a chronic diseases” should read “a chronic disease”.
Appropriate correction is required.
Claim Interpretation
Claims 1-11, 13, 15, 17-19 and 22 each recite phrases or clauses beginning with the term “optionally.” MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.” Thus, any “optional” phrases or clauses recited in a claim are interpreted as not limiting the claim.
Claim 18 recites, “wherein the self-tolerance is broken by the production of autoantibodies when the polyprotein is capable of being administered to the host.” It is noted that this limitation, as written, does not require the administration of the polyprotein to the host.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-11, 13, 15, 17-19, and 21-22 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 1 recites, “optionally at least two self-protein segments derived from a third self-protein of the host; and one or more T-cell epitopes of non-host origin in between and/or adjacent to the self-protein segments.” As written, it is unclear if the one or more T-cell epitopes are optional or required. In the interest of compact prosecution, the claim is interpreted such that the one or more T-cell epitopes are required element(s) of the vaccine composition.
Claims 1 and 17-18 recite the phrase “T-cell epitopes of non-host origin in between and/or adjacent to the self-protein segments.” The term “adjacent” in claims 1 and 17-18 is a relative term which renders the claim indefinite. The term “adjacent” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art at the time of filing would not be able to determine how close the T-cell epitope must be placed to the self-protein segments, and would not be able to determine whether there must be T-cell epitopes that are “in between and/or adjacent to” all of the self-protein segments or only at least two of the self-protein segments. In the interest of compact prosecution, T-cell epitopes immediately preceding or immediately following the self-protein segments are interpreted as “adjacent”.
Regarding claim 19, the claim recites, “The vaccine composition according to claim 1 or polyprotein… for a method of preventing or treating a disease in a subject, wherein the method comprises administering the vaccine composition or the polyprotein to the subject.” As written, it is unclear of the scope of the claim encompasses a composition or a method. See MPEP 2173.05(p): “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). In Katz, a claim directed to "[a] system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data" was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. Katz, 639 F.3d at 1318, 97 USPQ2d at 1749 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited "an input means" and required a user to use the input means was found to be indefinite because it was unclear "whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means.")” In the interest of compact prosecution, the claim is interpreted as being drawn to a composition because it depends upon claim 1 (which is drawn to a composition), and the “method of preventing or treating a disease in a subject” is interpreted as an intended use for the claimed composition.
Regarding claims 19-22, each of these claims recites a broader limitation (a polyprotein) together with a narrower limitation (a vaccine composition according to claim 1, which comprises the polyprotein). A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 21, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Clarification is requested.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-15 and 17-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a self-protein vaccine comprising an immunostimulatory oligonucleotide and an adjuvant conferring a depot effect capable of breaking self-tolerance in a host and breaking self-tolerance when administering the vaccine to the same population as the host, does not reasonably provide enablement for the claimed vaccine composition which does not require an adjuvant conferring a depot effect or a vaccine that breaks self-tolerance when administering the vaccine to a subject population that is different than the host. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The focus of the enablement inquiry is whether everything within the scope of the claim(s) is/are enabled, at the time of filing, without requiring undue experimentation to make or use the invention. The factors to be considered in determining whether a disclosure would require undue experimentation include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112(a) or 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. The claims are drawn to a polyprotein, a DNA encoding for the polyprotein, and/or an RNA encoding for the polyprotein and compositions thereof.
Claim 1 recites, “A vaccine composition for breaking self-tolerance against a self-protein of a host, wherein the vaccine composition is capable of raising autoantibodies against said self-protein when the vaccine composition is administered to the host, and wherein the vaccine composition comprises: a) a polyprotein, a DNA encoding for the polyprotein and/or an RNA encoding for the polyprotein, wherein the polyprotein comprises at least two self-protein segments derived from a first self-protein of the host; at least two self-protein segments derived from a second self-protein of the host; … and one or more T-cell epitopes of non-host origin in between and/or adjacent to the self-protein segments; and b) one or more immunostimulatory oligonucleotides.” As written, the scope of the claim encompasses vaccine compositions containing only the recited required elements capable of raising autoantibodies against the self-proteins and is capable of breaking self-tolerance against the self-protein in a host. The broadest reasonable interpretation of the claim is also that the “self-protein” may be any protein native to the host.
Claims 2-15 are dependent upon claim 1 and, like claim 1, they do not require the vaccine composition to comprise both one or more immunostimulatory oligonucleotides and an adjuvant conferring a depot effect in order to break self-tolerance to a self-protein of the host.
Claim 17 recites, “A polyprotein, a DNA encoding for the polyprotein and/or an RNA encoding for the polyprotein in a vaccine composition to break self-tolerance against a self-protein of a host, wherein the polyprotein comprises at least two self-protein segments derived from a first self-protein of the host; at least two self-protein segments derived from a second self-protein of the host;… and one or more T-cell epitopes of non-host origin in between and/or adjacent to the self-protein segments.” The interpretation of this claim is that a polyprotein, DNA encoding the polyprotein, or RNA encoding the polyprotein comprising only the recited required elements is capable of the intended use of breaking self-tolerance against a self-protein in a host. The broadest reasonable interpretation of the claim is also that the “self-protein” may be any protein native to the host.
Claim 18 recites, “A product comprising a polyprotein to break self-tolerance against a self-protein of a host, wherein the self-tolerance is broken by the production of autoantibodies when the polyprotein is capable of being administered to the host, and wherein the polyprotein comprises at least two self-protein segments derived from a first self-protein of the host; at least two self-protein segments derived from a second self-protein of the host;… and one or more T-cell epitopes of non-host origin in between and/or adjacent to the self-protein segments.” The interpretation of this claim is that a product comprising only the recited required elements is capable of breaking self-tolerance to a self-protein of a host as a result of the production of autoantibodies when the polyprotein is capable of being administered to the host. The broadest reasonable interpretation of the claim is also that the “self-protein” may be any protein native to the host.
Claim 19 recites, “The vaccine composition according to claim 1 or polyprotein comprising at least two self-protein segments derived from a first self-protein of the host; at least two self-protein segments derived from a second self-protein of the host;… and one or more T-cell epitopes of non-host origin in between and/or adjacent to the self-protein segments for a method of preventing or treating a disease in a subject.” The interpretation of this claim is that the vaccine or polyprotein containing on the recited required elements is capable of preventing or treating disease in a subject, and that the “subject” that the disease is treated in may be different than the “host” that the protein sequences are derived from. The broadest reasonable interpretation of the claim is also that the “self-protein” may be any protein native to the host.
Claims 20-22 are dependent upon claim 19 and, like claim 19, do not require the vaccine composition or polyprotein to comprise both one or more immunostimulatory oligonucleotides and an adjuvant conferring a depot effect in order to treat or prevent disease in a subject. Additionally, claims 20-22 do not require that the “host” species is the same species as the “subject” to which the composition is to be administered.
The state of the prior art and the level of predictability in the art: Saupe et al. (2015, FASEB J.; herein “Saupe”) teaches a vaccine composition comprising a fusion protein containing a self- and non-self-part, a CpG oligonucleotide (i.e., immunostimulatory oligonucleotide), and a depot adjuvant (Abstract and pg. 3253, right col., para. 1). Saupe teaches that the CpG oligonucleotide is a strong TLR agonist (pg. 3254, right col., para. 2) and that the depot adjuvant keeps the CpG at the site of the injection (Abstract). Saupe teaches that the lack of either the CpG or the depot adjuvant rendered the vaccine incapable of inducing an anti-self-antigen response, i.e., the vaccine is not capable of breaking self-tolerance against the self-antigen; thus, both an immunostimulatory oligonucleotide and a depot adjuvant are required for the function of breaking self-tolerance and raising autoantibodies against a self-protein (Abstract and pg. 3260, right col., para. 2).
Therefore, based on the prior art, one of ordinary skill in the art would recognize that a polynucleotide, DNA encoding the polynucleotide, or RNA encoding the polynucleotide or compositions thereof is not capable of breaking self-tolerance against a self-protein of a host and raising autoantibodies against the self-protein without the presence of both an immunostimulatory oligonucleotide and a depot adjuvant.
The amount of direction provided by the inventor and the existence of working examples: The specification teaches “a polyprotein, a DNA encoding for this polyprotein and/or an RNA encoding for this polyprotein for use in a vaccine composition to break self-tolerance against a self-protein of a host, wherein the polyprotein comprises at least two self-protein segments and one or more T-cell epitopes of non-host origin in between and/or adjacent to the at least two self-protein segments…. The research underlying the invention surprisingly found that a polyprotein comprising self-protein segments and non-host T-cell epitopes in between and/or adjacent to these self-protein segments is capable to break or circumvent the self-tolerance of a host against the self-protein segments of the polyprotein.” (pg. 5, ln. 15-31) However, the specification does not provide examples or data demonstrating that the polynucleotide alone is capable of breaking self-tolerance without the administration of one or more immunostimulatory oligonucleotides and a depot adjuvant. The specification also teaches a vaccine composition comprising the polyprotein, DNA encoding for the polyprotein, and/or RNA encoding for the polyprotein and one or more immunostimulatory oligonucleotides and that this vaccine is capable to induce a potent immune response against the self-protein segments of the polyprotein in the host to which the vaccine composition is administered.” (i.e., the host species is the same species as the subject) (pg. 6, ln. 7-32) However, the specification does not provide any examples or data demonstrating an immune response in a subject when such a vaccine composition (i.e., one that does not contain a depot adjuvant) is administered to a subject or when a vaccine composition comprising protein sequences from one species is administered to a different species.
The instant specification teaches several vaccine compositions that are capable of producing sufficient autoantibodies in the host: (a) canine IL-31 (cIL-31) polyprotein vaccine; (b) cIL-5 polyprotein vaccine; (c) cIL-13 polyprotein vaccine; (d) cIL-33 polyprotein vaccine; (e) cIL-4 polyprotein vaccine; (f) feline IL-31 polyprotein vaccine; (g) cIL-13-cIL-4 polyprotein vaccine; and (h) cIL-31-cIL-13-cIL-4 polyprotein vaccine (pg. 101-105). All of these vaccine compositions contained 1668-PTO and 2006-PTO (immunostimulatory oligonucleotides) and Polygen® (a depot adjuvant) (pg. 101-15). Each of these vaccine compositions is capable of raising sufficient autoantibody response against the target self-protein when the vaccine is administered to a subject that is the same species as the host (pg. 105-111). The instant specification also teaches the administration of canine IL-31 polyprotein and Polygen® as adjuvant to three dogs and states that the composition induced an immune response against the polyprotein, but is silent on whether the immune response was sufficient to break self-tolerance or raise autoantibodies (pg. 83, line 20 – pg. 84, line 5). The specification does not teach the administration of a polyprotein without both at least one immunostimulatory oligonucleotide and a depot adjuvant capable of inducing an autoantibody response sufficient to break self-tolerance against the self-protein. The instant specification also does not teach administration of a polyprotein comprising segments of two self-proteins of a host to a subject that is a different genus than the host (i.e., administering canine polyprotein compositions to a feline subject) that is capable of preventing or treating disease in the subject.
Therefore, what is enabled by the instant specification and working examples is narrow in comparison to the scope of the claims, and the specification does not provide enough information with which one may overcome the known unpredictability in the art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004)). The instant specification is not enabling across the full scope claimed because one cannot follow the guidance presented therein, or within the art at the time of filing, and make or use the claimed composition without first making a substantial inventive contribution.
In order to make the claimed invention(s), one of ordinary skill in the art would have to produce a polyprotein, DNA encoding the polyprotein, or RNA encoding the polyprotein or composition thereof that is capable of inducing an autoantibody response capable of breaking self-tolerance against a self-protein or is capable of preventing or treating disease without the use of one or more immunostimulatory oligonucleotides (see claims 17-22) and a depot adjuvant (see claims 1-15 and 17-22). This is not feasible because the art prior to the effective filing date of the claimed invention teaches that these components are necessary to break self-tolerance against a self-protein in a host, and the instant specification does not provide any teachings or guidance that contradict such a finding. No amount of experimentation will allow the full scope of the claimed invention to be used with a reasonable expectation because the prior art has demonstrated that a polynucleotide comprising segments of self-antigens of a host self-protein and one or more T-cell epitopes, alone or in combination with only one or more immunostimulatory oligonucleotides, is not capable of breaking self-tolerance of a self-protein or treating or preventing disease in a subject.
Additionally, regarding claims 19-22, neither the art nor the instant specification teach that a composition comprising self-antigens of a host of one species is capable of breaking self-tolerance in a subject of a different species. To make the claimed product with a reasonable expectation of success, one of ordinary skill in the art at the time of filing would have to identify self-proteins for which self-tolerance must be broken in a subject and that are shared between the subject species and a different host species.
Thus, without sufficient guidance from the art or the instant specification, to make such compositions would go beyond what is considered routine in the art.
Therefore, claims 1-15 and 17-22 are rejected under 35 U.S.C. 112(a) for failing to meet the enablement requirement.
Claims 1-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The broadest reasonable interpretation of the relevant claims is set forth in para. 21-26 above, and the teachings of the instant specification are set forth in para. 29 above.
Saupe teaches, “A small number of molecules have been identified as specifically expressed by neoplastic vasculature…. The reported lack of expression of these molecules in healthy tissue renders them highly interesting for targeted cancer therapies.” (pg. 3253, right col., para. 3) Although the teachings of Saupe are directed toward cancer therapy, this indicates that the selection of “self-proteins” or proteins native to the host for the purpose of breaking self-tolerance is limited to a relatively narrow selection of self-proteins, i.e., a vaccine for breaking self-tolerance against a self-protein would not use any given protein native to the host.
MPEP 2163(II)(A)(3)(a)(ii) states (emphasis added):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), 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 (see i)(C) above)….
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In contrast to the broad scope of self-proteins claimed, the instant specification only discloses polyproteins comprising segments of cytokines, specifically, cIL-31, cIL-5, cIL-13, cIL-33, cIL-4, fel-IL-31, and combinations thereof (pg. 101-105). These species of self-proteins are not representative of the full scope of self-proteins claimed because one of ordinary skill in the art would recognize that these self-proteins and those described by the art are associated with diseases and are expressed abnormally in subjects with such a disease; thus, one would recognize that self-proteins that are expressed normally or in healthy individuals, which are encompassed by the claim, are distinct from the narrow scope of self-proteins described in the specification. Therefore, the specification does not describe a sufficient variety of species to reflect the variation in the claimed genus.
Therefore, claims 1-22 are rejected under 35 U.S.C. 112(a) for failing to meet the written description requirement.
Claim Rejections - 35 USC § 112(d)
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.
Claims 4, 10, and 19-21 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.
Claim 4, which depends upon claim 1, recites, “wherein the polyprotein comprises two or three self-protein segments” but the open claim language “comprises” does not exclude the presence of additional self-protein segments. This limitation fails to further limit the scope of claim 1, which recites, “at least two self-protein segments” (i.e., two or more, including three, segments).
Claim 10, which depends upon claim 1, recites, “the first or second, or optionally third self-protein is derived from an optionally canine IL-13….” This claim fails to further limit the subject matter of claim 1 because all of the recited elements are optional, and therefore not limiting the structure of the vaccine composition. See MPEP 2111.04.
Claim 19, which depends upon claim 1, is interpreted as a composition reciting an intended use of “preventing or treating a disease in a subject, wherein the method comprises administering the vaccine or the polyprotein to the subject.” This intended use does not further limit the structure of the vaccine composition of claim 1 because claim 1 recites “the vaccine composition is capable of raising autoantibodies against said self-protein when the vaccine is administered to the host”, indicating that the vaccine composition of claim 1 is capable of an intended use of being administered to a subject.
Claim 21, which depends upon claim 20, recites, “wherein the subject is an animal selected from the group consisting of cattle, poultry, swine, and companion animals….” This limitation fails to narrow the subject matter of claim 20, which recites, “the subject is a mammal”, because poultry is not a mammal. Therefore, claim 21 broadens the subject matter of claim 20.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-6, 8-10, 16-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Klysner (WO 00/65058 A1) as evidenced by Hutchison et al. (2012, FASEB J.; herein “Hutchison”) in view of Saupe et al. (2015, FASEB J.; herein “Saupe”). This rejection is in view of a specific embodiment that is both enabled and obvious.
Regarding claims 1-4, 6, 8-10, and 17-19, Klysner teaches autovaccine constructs for breaking self-tolerance comprising at least two IL-5 protein segments and one or more tetanus toxoid T-cell epitopes (P2 and/or P30) between the two or more IL-5 segments (Fig. 5). Klysner also teaches that the vaccine may comprise DNA adjuvants, i.e., immunostimulatory oligonucleotides (pg. 37, line 5). Klysner also teaches that the autovaccine comprises a second moiety that is IL-4 or IL-13 (claims 14-15). Klysner also teaches that IL-4 and IL-13 are key effector molecules in in the pathophysiology of atopy and asthma (pg. 31, line 33 – pg. 32, line 7).
Regarding claim 5, Klysner teaches that the segments of the IL-5 protein contain at least one B-cell epitope (claims 3, 8, and 13).
Regarding claim 16, Klysner teaches that the vaccine may comprise an adjuvant, including aluminum adjuvants and oil formulations (pg. 37, ln. 4-5), which are adjuvants that form an antigen depot at the site of injection (as is evidenced by Hutchison, pg. 1272, left col., para. 2).
Regarding claim 20, Klysner teaches that the autovaccine may be administered to an animal, including a human (pg. 13, para. 1).
Regarding claim 22, Klysner teaches that the autovaccine is for therapy and prevention of asthma and chronic allergic diseases (pg. 1, para. 1).
However, Klysner does not teach a polyprotein comprising at least two segments of a second self-protein (i.e., the IL-4 or IL-13 moiety) with one or more T-cell epitopes in between or adjacent to the second self-protein segments, as in claim 1, or a vaccine comprising an immunostimulatory oligonucleotide, as in claim 1, or an adjuvant conferring a depot effect, as in claim 16, in a single embodiment.
Regarding claims 1-2, and 16-19, Saupe teaches a composition comprising self-antigens and foreign sequences in the vaccine protein as well as a potent pattern recognition receptor agonist like CpG oligonucleotides and a depot adjuvant to keep the CpG at the site of the injection (Abstract and pg. 3260, right col., para. 2). Saupe teaches that these elements are necessary for a potent self-antibody response (Abstract and pg. 3260, right col., para. 2). Saupe also teaches that the antibody response is a result of the T-helper cells directed against the non-self-region of the fusion protein (i.e., T cell epitopes) (pg. 3253, right col., para. 1).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the autovaccine construct of Klysner by inserting the tetanus toxoid T-cell epitopes into the IL-4 or IL-13 moiety of the construct and combine the resulting polyprotein with the immunostimulatory oligonucleotide and depot adjuvant disclosed in Klysner following the formulation of Saupe, thereby arriving at the invention of claims 1-6, 8-10, 16-20, and 22. The person of ordinary skill in the art would have been motivated to modify the IL-4 and/or IL-13 moiety because Klysner teaches that IL-4 and IL-13 are involved in asthma, just as IL-5, and Klysner teaches that the second moiety increases the responsiveness of the immune system (pg. 31, ln. 24-38); thus, one would be motivated to provoke an immune responses against IL-4 and IL-13 as well as IL-5. One of ordinary skill in the art would have been motivated to combine the autovaccine with the immunostimulatory oligonucleotide and adjuvant of both Klysner and Saupe in the way described by Saupe because Saupe teaches that the CpG nucleotide and depot adjuvant allow self-antigen vaccines to provoke a potent antibody response to the vaccine. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Saupe teaches that a CpG nucleotide and depot adjuvant are known to increase the anti-self-antibody response necessary to break self-tolerance when in combination with a vaccine protein comprising self-antigen and foreign T cell epitopes; thus, one would predict the same effect using a different self-antigen. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., polyprotein comprising self-protein segments from both a first and second self-protein of a host and one or more T cell epitopes of non-host origin, immunostimulatory oligonucleotides, depot adjuvants, B-cell epitopes, IL-5, IL-4, and IL-13) were known in the art. In addition, combining these elements yields a composition wherein the effectiveness of the vaccine is improved by the use of immunostimulatory oligonucleotides and a depot adjuvant; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-11 and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 14-23 of copending Application No. 18/262,975 (‘975). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 1, the ‘975 claims teach a vaccine composition for breaking self-tolerance against a self-protein of a host wherein the vaccine composition is capable of raising autoantibodies against said self-protein when the vaccine is administered to the host, and wherein the vaccine composition comprises: a) a polyprotein, a DNA encoding for the polyprotein and/or an RNA encoding for the polyprotein, wherein the polyprotein comprises at least two self-protein segments of the host; and one or more T-cell epitopes of non-host origin in between and/or adjacent to the at least two self-protein segments; and b) one or more immunostimulatory oligonucleotides (‘975 claim 1).
Regarding instant claim 2, the ‘975 claims teach that the one or more T-cell epitopes are selected from the group consisting of an artificial T-cell epitope peptide sequence and a T-cell epitope peptide sequence derived from a non-self-protein, optionally from a pathogenic protein (‘975 claim 2).
Regarding instant claim 3, the ‘975 claims teach the one or more T-cell epitopes are Tetanus toxin T-cell epitopes (‘975 claim 3).
Regarding instant claim 4, the ‘975 claims teach that the polyprotein comprises at least three self-protein segments (‘975 claim 4).
Regarding instant claim 5, the ‘975 claims teach the self- protein segment is (i) a full-length self-protein; or (ii) a truncated self-protein containing a B-cell epitope; or (iii) a derivative of a self-protein which has at least 80 % sequence identity, optionally at least 90 % sequence identity and optionally at least 95 % sequence identity to the full- length self-protein (‘975 claim 5).
Regarding instant claim 6, the ‘975 claims teach that the at least two self-protein segments are derived from a cytokine; optionally a cytokine selected from the group consisting of an IL-31, IL-4, IL-5, IL-13, IL-33, and TNF-alpha protein (‘975 claim 6).
Regarding instant claim 7, the ‘975 claims teach that the at least two self-protein segments are derived from an IL-31 protein (‘975 claim 7).
Regarding instant claim 8, the ‘975 claims teach that the at least two self-protein segments are derived from an IL-5 protein (‘975 claim 8).
Regarding instant claim 9, the ‘975 claims teach that the at least two self-protein segments are derived from an IL-4 protein (‘975 claim 9).
Regarding instant claim 10, the ‘975 claims teach that the at least two self-protein segments are derived from an IL-13 protein (‘975 claim 10).
Regarding instant claim 11, the ’975 claims teach that the at least two self-protein segments are derived from an IL-33 protein (‘975 claim 11).
Regarding instant claim 13, the ‘975 claims teach that the one or more immunostimulatory oligonucleotides are selected from the group consisting of A-class, B-class, and C-class immunostimulatory oligonucleotides, and mixtures thereof, and wherein optionally the one or more immunostimulatory oligonucleotides are selected from the group consisting of B-class immunostimulatory oligonucleotides (‘975 claim 14).
Regarding instant claim 14, the ‘975 claims teach that at least one or each of the one or more immunostimulatory oligonucleotides (i) comprise at least 75% sequence identity with the nucleic acid sequence of SEQ ID NO: 5 or SEQ ID NO: 6; or (ii) are selected from the group consisting of the nucleic acid sequence of SEQ ID NO: 5 and SEQ ID NO: 6 (‘975 claim 15). The ‘975 claims’ SEQ ID NO: 5 is identical to the instant SEQ ID NO: 5 and the ‘965 claims’ SEQ ID NO: 6 is identical to the instant SEQ ID NO: 6.
Regarding instant claim 15, the ‘975 claims teach that at least some phosphodiester moieties in the one or more immunostimulatory oligonucleotides have been chemically modified to increase nuclease resistance, optionally have been replaced by phosphorothioate moieties (‘975 claim 16).
Regarding instant claim 16, the ‘975 claims teach that the vaccine composition further comprises an adjuvant conferring a depot effect (‘975 claim 17).
Regarding instant claim 17, the ‘975 claims teach a Polyprotein, a DNA encoding for the polyprotein and/or an RNA encoding for the polyprotein for a vaccine composition to break self-tolerance against a self- protein of a host, wherein the polyprotein comprises at least two self-protein segments of the host and one or more T-cell epitopes of non-host origin in between and/or adjacent to the at least two self-protein segments (‘975 claim 18).
Regarding instant claim 18, the ‘975 claims teach a product comprising a polyprotein to break self-tolerance against a self-protein of a host, wherein the self-tolerance is broken by production of autoantibodies when the polyprotein is administered to the host, and wherein the polyprotein comprises at least two self-protein segments, and one or more T-cell epitopes of non-host origin in between and/or adjacent to the at least two self-protein segments (‘975 claim 19).
Regarding instant claim 19, the ‘975 claims teach the vaccine composition according to claim 1 adapted for a method of preventing or treating a disease in a subject, wherein the method comprises administering the vaccine composition to the subject (‘975 claim 20).
Regarding instant claim 20, the ‘975 claims teach the subject is a mammal including human and/or non-human animals (‘975 claim 21).
Regarding instant claim 21, the ‘975 claims teach the subject is an animal selected from the group consisting of cattle, poultry, swine, and companion animals optionally cats and dogs (‘975 claim 22).
Regarding instant claim 22, the ‘975 claims teach the disease is a chronic disease selected from the group consisting of an autoimmune disease, AIDS and cancer; or a pruritic condition, optionally selected from the group consisting of atopic dermatitis, eczema, psoriasis, scleroderma and pruritis; or an allergic condition, optionally selected from the group consisting of allergic dermatitis, summer eczema, urticaria, heaves, inflammatory airway disease, recurrent airway obstruction, airway hyper-responsiveness, chronic obstruction pulmonary disease and inflammatory process resulting from autoimmunity, wherein optionally the disease is a pruritic condition or an allergic condition, optionally atopic dermatitis (‘975 claim 23).
Although the claims at issue are not identical, they are not patentably distinct from each other because it would have been prima facie obvious to a person of ordinary skill in the art to add segments derived from a second self-protein of the host to the polyprotein of the ‘975 claims, thereby arriving at the invention of the instant claims. The person of ordinary skill in the art would have been motivated to make the modification in order to raise additional autoantibodies against the second self-protein, thereby breaking self-tolerance of the second self-protein. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because the structures of the polyprotein or vaccine are otherwise identical, so one would predict that the addition of segments derived from a second self-protein modified in the same manner as the first would produce an autoantibody response at least as well as that produced by the vaccine of the ‘975 claims. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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