DETAILED ACTION
Acknowledgment and entry of the Amendment submitted on 5/26/26 is made.
Claims 1, 2, 6 and 11-13 read on the elected invention and are under examination. Species vaccine comprising a protein; and SEQ ID NO: 3 in claim 2.
Claims 4, 5 and 7-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 4 and 5 have been amended to recite separate nucleic acid vaccines and are directed to an invention that is independent or distinct from the invention originally elected. See the Restriction Requirement mailed on 10/2/25. Protein vaccines and nucleic acid vaccines comprise biologically, structurally and chemically distinct products. Polypeptides, which are composed of amino acids, and polynucleotides, which are composed of purine and pyrimidine units, are structurally distinct molecules. They do not have the same mode of action when administered. These are patentably distinct products. Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 4 and 5 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Rejections - 35 USC § 112-2nd paragraph
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, 2, 6 and 11-13 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.
Claims 1, 2, 6 and 11-12 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the proteins from SEQ ID Nos: 1 and 3-29 in claims 1 and SEQ ID NOS: 4, 8, 10, 11, 12, 13, 15, 17, 20, 25, 26, 27 and 29 in claim 2; is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Protein vaccines and nucleic acid vaccines comprise biologically, structurally and chemically distinct products. Polypeptides, which are composed of amino acids, and polynucleotides, which are composed of purine and pyrimidine units, are structurally distinct molecules. They do not have the same mode of action when administered. These are patentably distinct products. Additionally, there are patentably distinct products within claims 1 and 2, e.g., proteins comprising different amino acid sequences which are structurally distinct chemical compounds and are unrelated to one another. The proteins would elicit different immunogenic responses and bind to different antibodies.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. NOTE: given the same source, T.cruzi, and high homology, 96.4%, the polypeptide with the amino acid sequence set forth in SEQ ID NO: 4 may be a true species of elected SEQ ID NO: 3. However, the polypeptides from other species of Trypansoma (SEQ ID NOS: 5-29) and with 28-89% homology to elected SEQ ID NO: 3 are different inventions, not different species. The nucleic acid vaccines of claims 4 and 5 should be removed from the claims.
Response to Applicants’ arguments:
Applicants argue that claim 1 is drawn to a protein vaccine and newly amended claims 4 and 5 are now separate and independent claims which are drawn to a nucleic acid vaccine. Applicants elected “protein vaccines” in the Election of 12/2/25. These two different inventions/products were originally written to be in the same claim. An Improper Markush rejection was made since they are different products. This is maintained. Claims 4 and 5, now that they have been amended to separate individual nucleic acid vaccines are directed to an invention that is independent or distinct from the invention originally claims for the reasons stated above and in the Restriction Requirement mailed on 10/2/25. Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 4 and 5 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Applicants also argue:
That the protein alternatives recited in claims 1 and 2 do not constitute an "arbitrary aggregation" of unrelated molecules but rather define a technically meaningful and structurally coherent group. As disclosed in the present application, these proteins are specifically identified as orthologous trypanosomatid proteins related to Tb927.6.4140 / Q586B2, sharing a common evolutionary origin and conserved structural and functional features. This relationship is not merely asserted but is explicitly supported by the disclosure. In particular, page 12, paragraph 17, identifies the claimed proteins as part of a defined ortholog set, while Example 2 provides a detailed analysis of the evolutionary conservation of Q586B2 homologues across Trypanosomatidae and related taxa. These passages demonstrate that the claimed proteins form a biologically and technically unified class, linked by homology and conserved function, rather than an arbitrary or functionally unrelated selection. In the unpredictable arts, evolutionary kinship is the hallmark of a "recognized class." Citing these receptors together in a Markush group is as scientifically sound as grouping isotopes of the same element or members of a specific chemical genus.
Applicants argue that the proteins share a “significant structural element” that is essential to the common property or activity. Conserved Structural Architecture: As shown in FIGs. 1A and 1B, the recited proteins have highly conserved primary sequence domains as well as a preserved secondary structure throughout the members. Identical Technical Effect: As described in the application, all of the sequences can be used as the basis of a vaccine composition. The claimed invention exploits the common architecture and technical effect to provide vaccines. Therefore, the choice between the recited sequences is not one of disparate inventions, but of functionally equivalent members of a discrete family. Further demonstrating the unity of the group, FIGs. 1A and 1B provide an alignment between the various proteins recited in the claims. The alignment reveals: Significant Primary Sequence Identity: The members share 48% identity and at least 75% similarity (positives) over a broad 116-residue span. Conserved Functional Motifs: The alignment shows highly conserved regions, particularly the sequences giving rise to alpha helices and beta strands In the biological arts, this level of sequence conservation indicates that the similarity is not due to random chance but reflects a deep evolutionary and structural relationship. This evolutionary relationship is depicted in FIG. 2 of the present application.. Under MPEP § 2117, this shared "common core" of protein structure is more than sufficient to justify their inclusion in a single Markush group. Because the proteins share a common evolutionary origin and conserved structural motifs relevant to the claimed compositions, they meet the "community of properties" required by In re Harnisch. The grouping is scientifically recognized and non-arbitrary. In sum, the applicant demonstrated that a vaccine containing Tb927.6.4140, which is a protein derived from Trypanosoma brucei, exhibited efficacy in various mouse models of Trypanosomatidae infections, extending beyond models restricted to Trypanosoma brucei challenge. These findings, along with data illustrating the degree of identity among various homologues of Tb927.6.4140, indicate that: i. Tb927.6.4140 is a highly conserved protein; and therefore ii. various homologues of Tb927.6.4140 should show the capacity to elicit similar immune responses in animals in vivo; and therefore iii. immunization of mice with Tb927.6.4140 or its homologues of SEQ ID NOs 3-29 provides long-term protection against various species of Trypanosomatidae parasites, extending beyond the species that originally produce said Tb927.6.4140 homologue. Accordingly, the claimed group satisfies both the structural similarity and common utility requirements identified by the Office and cannot be characterized as an improper grouping of unrelated inventions.
These arguments have been fully and carefully considered but are not deemed persuasive. The polypeptides from other species of Trypansoma (SEQ ID NOS: 5-29) and with 28-89% homology to elected SEQ ID NO: 3. There is significant structural variability amongst these 26 different proteins and these proteins would not be expected to have the same immunological effect. The specification only provides examples with the full-length polypeptide set forth in SEQ ID NO: 1.
Claim Rejections - 35 USC § 112-Scope of Enablement
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, 2, 6 and 11-13 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 pharmaceutical composition comprising a protein having the amino acid sequence set forth in SEQ ID NO: 1 or 3 and an adjuvant; (and further comprising a pharmaceutically carrier- claim), and a vaccine composition comprising SEQ ID NO: 1 and an adjuvant.
does not reasonably provide enablement for:
A vaccine composition, the composition comprising: a protein having an amino acid selected from SEQ ID NO: 3 and an adjuvant.
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/or use the invention commensurate in scope with these claims.
The specification states that substitutions, additions, or deletions, may be made to the defined sequences; however, the specification provides no guidance as which amino acids may be changed without causing a detrimental effect to the protein and its function as a vaccine. It is unpredictable as to which amino acids could be removed and which could be added. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein’s sequence where amino acid substitutions can be made with a reasonable expectation of success are limited. Other positions are critical to the protein’s structure/function relationship, e.g., such as various positions or regions directly involved in binding, catalysis in providing the correct three-dimensional spatial orientation of binding and catalytic sites. These regions can tolerate only very little or no substitutions. Selective point mutation to one key residue could eliminate the function of the polypeptide. It could eliminate its functional properties. If the range of decreased binding ability after single point mutation of a protein antigen varies, one could expect point mutations in the protein antigen to cause varying degrees of loss of protection/function, depending on the relative importance to the binding interaction of the altered residue. Alternatively, the combined effects of multiple changes, as instantly claimed, in an antigenic determinant could again result in loss of function. A protein having multiple point mutations, or accumulated point mutations at key residues could create a new antigen that is precipitously or progressively unrecognizable. As stated above, Applicants have not shown the particular substitution and the result it produces. Applicants have provided no guidance to enable one of ordinary skill in the art how to determine, without undue experimentation, the effects of different amino substitutions and the nature and extent of the changes that can be made. It is expensive and time consuming to make amino acid substitutions at more than one position, in a particular region of the protein, in view of the many fold possibilities for change in structure and the uncertainty as to what utility will be possessed. See Mikayama et al. (Nov.1993. Proc.Natl.Acad.Sci. USA, vol. 90 : 10056-10060) which teaches that the three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. Amino acids owe their ‘significance’ to their inclusion in a pattern which is directly involved in recognition by, and binding to, the receptor and the significance of the particular amino acids and sequences for different amino acids cannot be predicted a priori, but must be determined from case to case by painstaking experimental study. The instant claims allow for substitutions with amino acids of vastly different properties and they do not recite the specific changes in the claims.
The working example in the instant specification uses the full-length protein comprising the amino acid sequence set forth in SEQ ID NO: 1 which is very different in homology to SEQ ID NO: 3. Claim 1 encompasses any protein that has 48% amino acid identity with SEQ ID NO: 1. However, the data provided in the application is limited to the protein with SEQ ID NO: 1 and there is no data provided for any other proteins encompassed by claim 1. Likewise, no data or working examples are provided for vaccines comprising any of the orthologous proteins with amino acids of SEQ ID NOs: 3-29 as set forth in the amended claims. The application does not provide any arguments as to why the effect reported for the protein with SEQ ID NO: 1 could plausibly be achieved by any other proteins encompassed by claims 1 and 2. The protein with the amino acid sequence set forth in SEQ ID NO: 1 was tested as a therapeutic target for trypanosomatids. Mice vaccinated with a vaccine composition comprising said protein showed a significant reduction in first peak parasitemia, coinciding with a prolonged survival after challenge with wild type T. b. brucei parasites. A cross-protective effect using this vaccine composition, was also demonstrated against two other trypanosomatid species: T. congolense (Tcl3) and T. evansi. The immunogenic and prophylactic efficacy of the recombinant protein with SEQ ID NO: 1 against Leishmania major infection was evaluated in BALB/c mice. The experiment showed that, irrespective of the vaccination, comparable amounts of parasites were present at the infection site. However, a statistically relevant inhibition of development of lesions was observed in the vaccinated mice. An effect is shown for the protein with SEQ ID NO: 1 but not for any mutation of said protein having at least 48% amino acid identity and no data is reported for any of the proteins with SEQ ID NO: 3-29.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
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/or use the invention commensurate in scope with these claims.
Response to Applicants’ arguments:
Applicants argue that the demonstration of a conserved orthologous protein family establishes its evolutionary conservation, structural homology and distribution across multiple species, thereby supporting its classification as a shared and functionally coherent antigenic target. i. Example 1 identifies Q586B2 / Tb927.6.4140 as a novel T. brucei protein and defines its structural features. ii. Example 2 demonstrates that Q586B2 / Tb927.6.4140 belongs to a conserved orthologous protein family across trypanosomatids and related taxa, and establishes its evolutionary conservation, structural homology, and distribution across multiple species, thereby supporting its classification as a shared and functionally coherent antigenic target. iii. Example 3 describes the recombinant production and characterization of Q586B2, including its oligomeric state, tautomerase activity, localization, generation of corresponding nanobodies, and cross-species recognition. iv. Example 4 demonstrates that Q586B2 is secreted by parasites and induces cytokine responses, including IL-10, in cultured macrophages and in vivo in mice. V. Example 5 demonstrates that Q586B2 immunization reduces parasitemia and prolongs survival after challenge in multiple trypanosomatid infection models. vi. Example 6 demonstrates efficacy of Tb927.6.4140 protein in a Leishmania major challenge model. These arguments have been fully and carefully considered but are not deemed persuasive. The working example in the instant specification uses the full-length protein comprising the amino acid sequence set forth in SEQ ID NO: 1 which is very different in homology to SEQ ID NO: 3. The data provided in the application is limited to the protein with SEQ ID NO: 1 and there is no data provided for any other proteins encompassed by claim 1. Likewise, no data or working examples are provided for vaccines comprising any of the orthologous proteins with amino acids of SEQ ID NOs: 3-29 as set forth in the amended claims. The application does not provide any arguments as to why the effect reported for the protein with SEQ ID NO: 1 could plausibly be achieved by any other proteins encompassed by claims 1 and 2. The protein with the amino acid sequence set forth in SEQ ID NO: 1 was tested as a therapeutic target for trypanosomatids. Mice vaccinated with a vaccine composition comprising said protein showed a significant reduction in first peak parasitemia, coinciding with a prolonged survival after challenge with wild type T. b. brucei parasites. A cross-protective effect using this vaccine composition, was also demonstrated against two other trypanosomatid species: T. congolense (Tcl3) and T. evansi. The immunogenic and prophylactic efficacy of the recombinant protein with SEQ ID NO: 1 against Leishmania major infection was evaluated in BALB/c mice. The experiment showed that, irrespective of the vaccination, comparable amounts of parasites were present at the infection site. However, a statistically relevant inhibition of development of lesions was observed in the vaccinated mice. An effect is shown for the protein with SEQ ID NO: 1 but not for any mutation of said protein having at least 48% amino acid identity and no data is reported for any of the proteins with SEQ ID NO: 3-29.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
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.
Claim(s) 1, 2, 6 and 11-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dias et al (J. Structural Biol. 211(2). May 2020, pages 1-12; provided by Applicants), Hebert L., et al (Submitted Sep-2016; Accession No. A0A1G4I0X4; January 18, 2017 public- Uniprot database) and Berna et al "Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi."; Microb. Genom. 0:0-0(2018). Accession No. A0A2V2X6Q0; 12-SEP-2018, integrated into UniProtKB/TrEMBL) and Jackson et al (Accession No. A0A2V2X60; EMBL/Genbank. 10/19/11 From: Proc. Natl. Acad. Sci. U.S.A. 109:3416-3421. 2012),
in view of Linares et al (US 2013/108660; provided by Applicants),
Berna et al discloses a Trypanosoma protein with an amino acid sequence that is 100% identical to SEQ ID NO: 3, over all 116 amino acids identical; 96.4% identical to SEQ ID NO: 4; and 56.6% to Applicant’s SEQ ID NO: 1. See Accession No. A0A2V2X6Q0 in supplemental content tab, Uniprot, and attached reference on PTO-892.
Hebert et al disclose a Trypanosoma protein with 100% identity to Applicants’ SEQ ID NO: 1. See Submitted Sep-2016; Accession No. A0A1G4I0X4; January 18, 2017 public- Uniprot database in supplemental content tab and attached reference on PTO-892.
Dias discloses a protein having the amino acid sequence set forth in SEQ ID NO: 1 (Trypanosoma brucei brucei hypothetical protein Tb927.6.4140, is the protein set forth in Applicant’s SEQ ID NO: 1). Dias et al discloses the crystal structure of the T. cruzi protein Q4D6Q6 and mentions its orthologous gene Tb927.6.4140 from Trypanosoma brucei brucei (54% sequence identity to Applicants’ SEQ ID NO: 1). See column 1, first full paragraph, on page 2.
Jackson et al researches antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species and teaches a protein with 64.3% to Applicant's SEQ ID NO: 1. Accession No. F9WFX2.
However, Berna, Hebert and Berna do not particularly teach the use of the proteins as a vaccine along with an adjuvant.
Linares discloses a Trypanosoma vaccine for protecting against infections by an African trypanosome selected from Trypanosoma congolense, Trypanosoma vivax, Trypanosoma evansi and/or Trypanosoma brucei, and preferably against infections by Trypanosoma congolense. Paragarph [0061]-[0062] show that adjuvants are commonly used in such compositions, as well as prominent Trypanosoma proteins.
Although the primary references do not specifically recite the use of the Trypanosoma proteins as a vaccine, a “vaccine” is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. An adjuvant is an obvious inclusion to a parasitic protein composition for further research and to raise antibodies as shown in the teachings of Linares and it would have been prima facie obvious to combine an adjuvant and/or pharmaceutically acceptable carrier with a known Trypanosoma protein. It is noted that the instant specification does not teach any results with SEQ ID NOS: 3-29, yet also suggests they be combined with an adjuvant for research/vaccination purposes.
Response to Applicants’ arguments:
Applicants argue, in summary:
The cited primary references, as summarized in the Office Action, at most disclose proteins or homologous sequences corresponding to Applicant's SEQ ID NO:1 or SEQ ID NO:3, or structural information relating thereto. The Office Action expressly acknowledges that the primary references "do not particularly teach the use of the proteins as a vaccine along with an adjuvant." This is a critical deficiency. The present application is not directed merely to the existence of these proteins. Rather, it identifies them as biologically significant antigens with protective vaccine utility. The application shows that Q586B2 / Tb927.6.4140 is a secreted parasite-derived virulence factor involved in early-stage infection and immune modulation (Examples 3 and 4). Nothing in Dias, Jackson, Hebert, or Berna, teaches or suggests that the recited proteins would have this role or that they would function as protective vaccine antigens such that composition including them would merit the addition of an adjuvant. Linares generally teaches trypanosome vaccines and adjuvants, but that does not render obvious every trypanosome protein, or nucleic acid molecule encoding any such protein, as a vaccine antigen. The rationale of the Office thus amounts to an "obvious to try" rationale. In sum, the Office finds that the recited proteins are known and thus it would be obvious to include them in compositions including an adjuvant for use as a vaccine. As set forth in MPEP 2143(I)(E), an "obvious to try" rationale requires "a finding that there was a finite number of identified, predictable potential solutions to the recognized need or problem." The applicants submit that the Office has not made such a finding. The Office has not identified that finite number of potential solutions. To the contrary, the position of the Office appears to assert that all Trypanosoma proteins are solutions and that each of these proteins would predictably be useful as an immunogen in conjunction with an adjuvant. A person of ordinary skill in the art at the time of the present application would have understood that this was not the case. The Office Action identifies no teaching in the art that would have led the skilled person to choose the presently claimed proteins from the universe of parasite proteins with a reasonable expectation that they would confer the experimentally demonstrated protective effects. To hold otherwise would mandate the conclusion that every protein, from every non-human species, would be obvious to include in a composition including an adjuvant. To the contrary, the present application demonstrates that the recited proteins have a previously unrecognized biological role in parasite establishment and immunomodulation. Example 4 shows secretion of Q586B2 and induction of IL-10 and other cytokines. Example 5 then demonstrates that immunization with Q586B2 confers protective effects in multiple challenge models. The present application provides substantial evidence of non-obvious results. Example 5 shows that prophylactic treatment / immunization with Q586B2 in the presence of adjuvant results in a significant reduction in first-peak parasitemia and prolonged survival after challenge with T. b. brucei, T. congolense, and T. evansi. Example 5 expressly describes these findings as a cross- protective effect against multiple trypanosomatid species. Example 6 further reports statistically relevant inhibition of lesion development in a Leishmania major infection model following vaccination with Tb927.6.4140. These results are highly significant and would not have been expected from the mere existence of sequence entries or structural data in the art. The cited art provides no reasoned expectation that the claimed proteins, when formulated with adjuvant, would produce this breadth of protective efficacy.
These arguments have been fully and carefully considered but are not deemed persuasive. The protein with SEQ ID NO: 1 has been previously described as recited in the rejection above. Diaz discloses the crystal structure of the T. cruzi protein Q4D6Q6 and mentions its orthologous gene Tb927.6.4140 from Trypanosoma brucei brucei. Diaz does mention Q4D6Q6 as a potential anti-trypanosomal drug target, however, it could not have been predicted by the skilled person that Q4D6Q6 or its homologue with SEQ ID NO: 1 would induce a protective immune response and would be a good antigen for vaccination. Additionally, the data provided in the application is limited to the protein with SEQ ID NO: 1 and there is no data provided for any other proteins encompassed by claim 1. Likewise, no data is provided for the orthologous proteins with SEQ ID NO: 3-29 as set forth in the amended claims. The application does not provide any arguments as to why the effect reported for the protein with SEQ ID NO: 1 could plausibly be achieved by any other proteins encompassed by claims 1 and 2. As a result, based on the data available the problem defined above cannot be considered to be solved by any other protein than the protein with SEQ ID NO: 1. It follows that no inventive step can be acknowledged over the whole scope of claims 1 or 2. The same negative reasoning applies to all the other claims which are not limited to the protein with SEQ ID NO: 1. a “vaccine” is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. An adjuvant is an obvious inclusion to a parasitic protein composition for further research and to raise antibodies as shown in the teachings of Linares and it would have been prima facie obvious to combine an adjuvant and/or pharmaceutically acceptable carrier with a known Trypanosoma protein. It is noted that the instant specification does not teach any results with SEQ ID NOS: 3-29, yet also suggests they be combined with an adjuvant for research/vaccination purposes.
Status of Claims:
No claims are presently allowed.
Prior art, not presently relied upon:
Matthews J., et al. "An alternative strategy for trypanosome survival in the mammalian bloodstream revealed through genome and transcriptome analysis of the ubiquitous bovine parasite Trypanosoma (Megatrypanum) theileri.";Submitted (MAR-2017) to the EMBL/GenBank/DDBJ databases; Accession No. A0A1X0P259. 59.3% identity to Applicant’s SEQ ID NO: 1.
Bradwell et al "Genomic comparison of Trypanosoma conorhini and Trypanosoma rangeli to Trypanosoma cruzi strains of high and low virulence."; ( BMC Genomics 19:770-770(2018). 58.1% identical to Applicant’s SEQ ID NO: 1. Accession no. A0A422Q5A3;
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.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached on (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 8/6/26
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