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 .
Claims 1-18, 21 and 23 are pending and are under examination. Claims 7-8, 17, 18 and 21 are withdrawn. Claims 1-6, 9-16 and 23 are under examination.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-16 and 23 and species SEQ ID NO: 1 in the reply filed on 11/3/25 is acknowledged.
It is noted that the restriction requirement required an election from SEQ ID NO: 5-60. However, since Applicant’s have not elected any from SEQ ID NO: 5-60, the examination will be based on Applicant’s election of SEQ ID NO: 1 and along with SEQ ID NO: 3.
Applicant’s traversal is on the ground(s) that the distinguishing and unifying feature of the present claims over wright is the elected FLA1 binding protein which provides the technical effect of imparting onto the resulting vaccine applicability against multiple species of trypanosome which contain orthologs of FLA1 binding proteins, such as Leishmania and provides effective protection against both T. congolense and T. vivax. Applicants state that the present invention provides an improved vaccine to prevent animal African trypanosomiasis (AAT) which may be caused by multiple species of trypanosome, such as T congolense, T. vivax or Leishmania, or by both T. congolense and T. vivax. Applicants argue that the provision of an FLA1 binding protein as part of the vaccine would not have been obvious to an ordinary skilled artisan because the cited art by Wright fails to teach or even suggest that its disclosed proteins are FLA1 binding proteins or that they may be used in vaccines with applicability against multiple trypanosome species and this finding is for the first time disclosed in the present application and reflected in the present claims.
This is not found persuasive because evidence of secondary considerations is not considered for lack of unity requirement in accordance with PCT Rule 13.1 (Unity of Invention) and 37 CFR 1.499 (Unity of Invention during National Stage).
The instant application is a national stage (filed under 35 USC 371) application of an international application and the lack of unity requirement was carried out in accordance with PCT Rule 13.1 (Unity of Invention) and 37 CFR 1.499 (Unity of Invention during National Stage). See MPEP chapters 1850 and 1893.03. “Lack of unity of invention may be directly evident "a priori," that is, before considering the claims in relation to any prior art, or may only become apparent "a posteriori," that is, after taking the prior art into consideration.
For example, independent claims to A + X, A + Y, X + Y can be said to lack unity a priori as there is no subject matter common to all claims.
In the case of independent claims to A + X and A + Y, unity of invention is present a priori as A is common to both claims. However, if it can be established that A is known, there is lack of unity a posteriori, since A (be it a single feature or a group of features) is not a technical feature that defines a contribution over the prior art.” The expression "special technical features" is defined in PCT Rule 13.2 as meaning those technical features that define a contribution which each of the inventions, considered as a whole, makes over the prior art. (See MPEP chapter 1850 under Determination of Unity of Invention).
The independent invention is drawn to a trypanosomal vaccine comprising a flagellum adhesion (FLA1) protein 1 binding protein. Flagellum adhesion protein 1 binding protein is known. See Sun et al. J Cell Sci. (2013)126 (2): 520-53, cited in IDS. Sun et al disclose a flagellum adhesion protein 1 binding protein (FLA1BP) See abstract.
Since it is established that the flagellum adhesion protein 1 (FLA1) binding protein (FLA1BP) set forth in independent claim 1 is known, there is lack of unity a posteriori, and thus FLA1BP is not a technical feature that defines a contribution over the prior art.”
Claims 7-8, 17, 18 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/3/2025.
Information Disclosure Statement
The information disclosure statement filed 6/26/23 has been considered and an initialed copy is enclosed.
Drawings
The drawings are objected to because the font and graph data points in figure 2-4 are too tiny to decipher.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
See paragraph 77.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
Abstract
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract recites language which is implied such as “the present invention relates”. Appropriate correction is required. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Title
The title of the invention is objected to because of the word “novel” which should not be included in the title. See MPEP 606 and 37 CFR 1.72.
Claim interpretation - 35 U.S.C. 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Such a claim limitation that uses the word “means” is found in claim 23: “…means for administering the vaccine composition…” in claim 23. The corresponding structures, materials are acts to perform the function are interpreted to be those found in paragraph 53-54, and equivalents thereof.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation is found in claim 16: “adapted for” . The corresponding structures, materials are acts to perform the function are interpreted to be those found in paragraph 53-54, and equivalents thereof.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections 35 USC § 112- Improper Markush Grouping
Claims 2-3 and 4-5 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 a protein vaccine and a polynucleotide vaccine 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:
The protein vaccine which is composed of amino acids, and the polynucleotide vaccine, which are composed of purine and pyrimidine units, are structurally distinct molecules. These vaccines act differently when administered and the efficacy of one cannot be extrapolated to the other. Additionally, a protein can also be recovered from a natural source using by biochemical means. For instance, the polypeptide can be isolated using affinity chromatography. Furthermore, searching both the inventions together would impose a serious search burden.
In the instant case, the search of the polypeptides and the polynucleotides are not coextensive. The inventions of have a separate status in the art as shown by their different classifications. Where sequence information is provided, the sequences are searched in different databases. There is also search burden for both inventions in the non-patent literature as a priori journal articles dedicated to polypeptides may not describe the polynucleotide and vice versa. For example, non-patent literature dedicated to genomic analysis may not reveal the polypeptide. In the instant application, the specification fails to provide the nucleic acid sequence which encodes the protein.
For these reasons, it would be burdensome to search the inventions together.
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.
Claim Rejections - 35 USC § 112 1st Paragraph Written Description
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 1-6, 9-16 and 23 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.
Claim 1 is drawn to a trypanosomal vaccine comprising a flagellin adhesion protein 1 (FLA1) binding protein. This covers a large and variant genus of FLA1 binding proteins, the genus comprising species with widely different structures.
For example. the FLA1 binding protein comprises a sequence selected from:
an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 which comprises FLA1 binding protein that comprise fragment of SEQ ID NO: 1 or SEQ ID NO: 3 due to the recitation “an amino acid sequence as set forth in SEQ ID NO: 1 or “an amino acid sequence as set forth in SEQ ID NO: 3;
a sequence having at least 90% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3 - up to 10% of the amino acid sequence can vary;
a fragment of SEQ ID NO: 1 or SEQ ID NO: 3; and
a nucleic acid sequence encoding the protein, where the protein is interpreted to mean any of the aforementioned proteins.
The specification does not disclose the common structure of members of this genus of FLA1 binding proteins that correlates with the function as a vaccine.
The general knowledge and level of skill in the art does not supplement the omitted description of such fragments that are immunogenic.
While a person of ordinary skill in the art can use bioinformatics as a tool to identify predict immunogenic regions of proteins and test those immunogenic regions in an animal model of Trypanosoma infection, to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Possession of a claimed genus may not be shown by describing how to obtain members of the genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69USPQ2d at 1895. The written description provision of 35 U.S.C. § 112 are severable from its enablement provision Vas-Cath, Inc. v. Mahurkar, 1115.
Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention”. “Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement”. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
SEQ ID NO: 1 is a fragment of the full length binding protein as it corresponds to the ectodomain of a cell surface T. congolense protein known as TcIL3000_0_17090 whose full length is SEQ ID NO: 2. See paragraph 22 and 27-29.
SEQ ID NO: 3 is a fragment of the full length binding protein as it corresponds to the ectodomain of a cell surface T. congolense protein known and TcIL3000_0_35140 whose full length is SEQ ID NO: 4. See paragraph 31-36.
Vaccination with the ectodomain TcIL3000_0_17090 together with QUIL A adjuvant conferred protection in a murine model of T. congolense infection. A different but related protein TcIL3000_0_35140 sharing greater that 98% amino acid identity to the ectodomain of TcIL3000_0_17090 also together with QUIL A adjuvant conferred protection in a murine model of T. congolense infection. See paragraph 104-105 of the specification.
However, these are not representative of the genus of proteins that function as a trypanosome vaccine. The specification does not describe any fragment of SEQ ID NO: 1 or SEQ ID NO: 3; or other sequence that vary by up to 10% from SEQ ID NO: 1 or SEQ ID NO: 3; or other FLA1 binding protein that comprise a fragment of SEQ ID NO: 1 or SEQ ID NO: 3 i.e. “an amino acid sequence as set forth in SEQ ID NO: 1 or “an amino acid sequence as set forth in SEQ ID NO: 3 that confers protection with or without adjuvant from Trypanosoma infection.
In addition, the specification also does not describe vaccine compositions with diluents, carriers, other saponin adjuvants, or excipients having similar results seen for TcIL3000_0_35140 or TcIL3000_0_17090 with QUIL A adjuvant.
The specification adequately describes subcutaneous administration for TcIL3000_0_35140 or TcIL3000_0_17090 with QUIL A adjuvant (paragraphs 104-105), but does not appear to adequately describe other routes of administration such as epidural or mucosal administration such as intranasal, oral, pulmonary or rectal administration and other parenteral administration routes. Thus, by extension, the specification fails to teach compositions “adapted for” these routes.
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
The disclosure of only two species with the recited activity encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615.
There is unpredictability in the Trypanosoma vaccine art for various reasons one of the most important of which is antigenic variation. Previous attempts to develop subunit vaccines against African trypanosome infections have highlighted the difficulties in overcoming the immune evasion strategies such as antigenic variation that have been evolved by these parasites to enable them survive in host blood. See Autheman et al (Nature 595, 96–100 (2021) cited in IDS) p. 96 first column. Furthermore, findings in experimental mice models of infection may not translate to livestock such as goats in which the parasites cause trypanosomiasis. See Autheman et al at page 100 under discussion.
Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed."
In view of these considerations, Applicants as of the effective filing date were not in possession of the genus being claimed.
Claim Rejections - 35 USC § 112 – Scope of enablement
Claims 1-6, 9-16 and 23 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 Trypanosomal vaccine comprising a flagellum adhesion protein 1 binding protein comprising SEQ ID NO: 1 or SEQ ID NO: 3 and QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria), does not reasonably provide enablement for vaccines comprising flagellum adhesion protein 1 binding protein sequence variants and including sequence variants without adjuvant or with other adjuvants. 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.
Factors to be considered in determining whether undue experimentation is
required, are set forth in in re Wands, 8 USPQ2d 1400. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or
unpredictability of the art and (8) the breadth of the claims. Although all the factors were considered, the most relevant ones are discussed below.
The nature of the invention is trypanosomal vaccine comprising sequence a flagellum adhesion protein 1 (FLA1) binding protein.
The breadth of the claims encompasses variant FLA1 binding protein sequences and nucleic acid sequences encoding these proteins. The claims require the function of a trypanosomal vaccine.
For example, the FLA1 binding protein comprises a sequence selected from:
an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 which comprises FLA1 binding protein that comprise fragment of SEQ ID NO: 1 or SEQ ID NO: 3 due to the recitation “an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3;
a sequence having at least 90% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3;
a fragment of SEQ ID NO: 1 or a fragment of SEQ ID NO: 3; and
a nucleic acid sequence encoding the protein which is interpreted to mean any of the aforementioned proteins.
SEQ ID NO: 1 is a fragment of the full length binding protein as it corresponds to the ectodomain of a cell surface T. congolense protein known as TcIL3000_0_17090 whose full length is SEQ ID NO: 2. See paragraph 22 and 27-29.
SEQ ID NO: 3 is a fragment of the full length binding protein as it corresponds to the ectodomain of a cell surface T. congolense protein known and TcIL3000_0_35140 whose full length is SEQ ID NO: 4. See paragraph 31-36.
Vaccination with the ectodomain TcIL3000_0_17090 together with QUIL A adjuvant conferred protection in a murine model of T. congolense infection. A different but related protein TcIL3000_0_35140 sharing greater that 98% amino acid identity to the ectodomain of TcIL3000_0_17090 also together with QUIL A adjuvant conferred protection in a murine model of T. congolense infection. See paragraph 104-105 of the specification.
The specification does not correlate any immunogenic response elicited by any other variant FLA1 binding protein e.g. fragment of SEQ ID NO: 1 or SEQ ID NO: 3; or FLA1 binding protein comprising fragment of SEQ ID NO: 1 or SEQ ID NO: 3 or those that vary by up to 10% from SEQ ID NO: 1 or SEQ ID NO: 3with or without adjuvant with or protection against Trypanosoma infection.
The specification also does not correlate the immune response generated with FLA1 binding protein with diluents, carriers, other saponin adjuvants, or excipient having similar results seen for TcIL3000_0_35140 or TcIL3000_0_17090 with QUIL A adjuvant.
The specification correlates the immunogenic response TcIL3000_0_35140 or TcIL3000_0_17090 with QUIL A adjuvant via subcutaneous administration with protection against Trypanosome infection but does not appear to correlate immune-protective responses with other routes of administration such as epidural or mucosal administration such as intranasal, oral, pulmonary or rectal administration and other parenteral administration routes.
There is unpredictability in the Trypanosoma vaccine art for various reasons one of the most important of which is antigenic variation. Previous attempts to develop subunit vaccines against African trypanosome infections have highlighted the difficulties in overcoming the immune evasion strategies such as antigenic variation that have been evolved by these parasites to enable them survive in host blood. See Autheman et al (Nature 595, 96–100 (2021). https://doi.org/10.1038/s41586-021-03597-x) p. 96 first column. Furthermore, findings in experimental mice models of infection may not translate to livestock such as goats in which the parasites cause trypanosomiasis. See Autheman et al at page 100 under discussion.
"The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art." "The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling". The MPEP further states that physiological activity can be considered inherently unpredictable. Thus, Applicant assumes a certain burden in establishing that inventions involving physiological activity are enabled. (MPEP 2164.03).
Additional guidance or direction would be required to make and use the full scope of the invention
In conclusion, the specification, is enabling for a Trypanosomal vaccine comprising SEQ ID NO: 1 or SEQ ID NO: 3 with QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria).
Claim Rejections - 35 USC § 112 4th paragraph
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.
Claim 9 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 9 is drawn to a pharmaceutical composition comprising a trypanosomal vaccine of claim 1. Claim fails to limit the scope of claim 9 because the subject matter of claim 1 and claim 9 are the same despite the additional wording of “pharmaceutical composition” in claim 9. A vaccine is a pharmaceutical composition, therefore the subject matter of claim 9 is not a further limitation of the subject matter of claim 1. 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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-6, 9-12, 15, 16 and 23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) a trypanosomal vaccine, comprising a flagellin adhesion protein 1 (FLA1) binding protein.
STEP 1: THE CLAIMS ARE DRAWN TO A COMPOSITION OF MATTER
STEP 2A PRONG ONE – THE CLAIM RECITES A JUDICIAL EXCEPTION -SEE MPEP 2106.4
The trypanosomal vaccine, comprising a flagellin adhesion protein 1 (FLA1) binding protein is a product of nature as it is from the Trypanosome parasite. FLA1 binding protein is a glycosylated transmembrane protein essential for flagellum attachment and cell division.
SEQ ID NO: 1 is a fragment of the full length binding protein as it corresponds to the ectodomain of a cell surface T. congolense protein known and TcIL3000_0_17090 whose full length is SEQ ID NO: 2. See paragraph 22 and 27-29.
SEQ ID NO: 3 is a fragment of the full length binding protein as it corresponds to the ectodomain of a cell surface T. congolense protein known and TcIL3000_0_35140 whose full length is SEQ ID NO: 4. See paragraph 31-36.
A nucleic acid sequence encoding FLA1 binding protein comprising SEQ ID NO: 1 or comprising SEQ ID NO: 3 encompasses genomic DNA of the parasite.
FLA1 binding protein SEQ ID NO: 3 has 99 % sequence identity with SEQ ID NO: 1.
SEQ ID NO: 1 and SEQ ID NO: 3 are fragments of full length FLA1 binding protein and both are nature based and not substantially different because the ectodomain (SEQ ID NO:1 and SEQ ID NO: 3) still maintains the same sequence as found in the full length protein and so does the fragment of the ectodomain.
In claim 10-12, the composition further comprises an invariant flagellum antigen. This is also a product of nature the antigen is from T. vivax (see paragraph 67). Each content of such a composition is compared to the corresponding natural counterpart as the combination of proteins may not exist in nature. Each antigen on their own are product of nature and there is no evidence that the proteins react together resulting in something "markedly different”. The composition is thus a nature-based composition that is not “markedly different” as each antigen continues to behave as it normally would.
Thus, the subject matter of claims 1-6 and 9-12 are products of nature without significantly more.
As per claim 15, pharmaceutically acceptable carrier, diluent or excipient encompasses liquid such as milk or water. The combination of milk or water and protein is nature based, does not naturally exist in nature and thus each component is compared to its closest naturally occurring counterpart. Each of the binding protein and milk/water on their own are product of nature and there is no evidence that the milk/water and the bacterium react together resulting in something "markedly different”. See Ass 'n for Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct. 2107, 2117 (2013).
In claim 16, the combination of the binding protein and milk/water is a liquid and thus is adapted for parenteral administration, epidural administration and mucosal administration. Essentially, claim 16 encompasses a combination of bacteria and milk/water, for example, and is a product of nature as analyzed in the preceding paragraph.
STEP 2A PRONG TWO – THE CLAIM DOES NOT RECITE ADDITIONAL ELEMENTS THAT INTEGRATE THE JUDICIAL EXCEPTION INTO A PRACTICAL APPLICATION. SEE MPEP 2106.4
Next, the claim as a whole is analyzed to determine whether any additional element or combination of elements that integrates the judicial exception into a practical application is recited.
Claims 1-6, 9-12 and 15-16 do not recite additional elements that integrate the judicial exception into a practical application such a particular treatment or prophylaxis for a disease or medical condition i.e. affirmatively reciting an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of said action is a step of administering the bacterium or the composition comprising the bacterium to a subject and not merely an intended use of the bacteria. See MPEP 2106.04(d)(2). The analysis of these claims is concluded at this step.
STEP 2B – THE CLAIMS DO NOT AMOUNT TO SIGNIFICANTLY MORE. SEE MPEP 2106.05.
Claim 23 is drawn to a kit of parts comprising the vaccine composition of claim 9, a medical instrument or other means for administering the vaccine composition and instructions for use. The claim as a whole is analyzed to determine whether any additional element, or combinations of elements, is sufficient to ensure that the claim amounts to significantly more than the exceptions. Integration requires an additional element in the claim to apply, rely on, or use the judicial exception in a manner than imposes a meaningful limit on the judicial exception. As claimed the vaccine composition is not incorporated into the medical instrument or into the broadly recited other means for administering the vaccine composition. In addition, the instructions are not functionally related to the vaccine composition to produce a new product. The FLA1 binding protein remains the same despite presence of instructions that are not functionally related. Thus, claim 23 does not recite any meaningful additional limitations, modification(s) or transformation(s) that sufficiently ensures that the claim amounts to significantly more than the exception.
In conclusion, the claims does not qualify as eligible subject matter under 35 USC 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 4, 6, 9,15, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jackson et al. 2012 (Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species; PNAS 109(9):3416- 3421; cited in IDS).
Jackson teaches compositions comprising genomic sequences derived of Trypanosoma congolense strain IL3000 including a 100% sequence match for SEQ ID NO: 1 and SEQ ID NO:3 as evidenced by the alignment in Appendix B and C respectively. Thus, with regards to claims 1-5 and 20; based on the art-recognized correspondence between a nucleic acid sequence and its encoded amino acid sequence, the teachings of Jackson also meet the limitations in these claims; see Ex parte Chuang, BPAI 2008; In re Kubin, 561 F.3d 1351, 90 USPQ2d 1417 (Fed. Cir. 2009); and MPEP 2144.
Furthermore, T. congolense parasite comprises the FLA1 binding protein and the nucleic acid encoding said protein and the parasite does not exist in vacuum and is necessarily in carried by a pharmaceutically acceptable carrier, diluent or excipient. See under materials and methods genome sequencing and annotation of T. congolense IL3000.
It is noted claim 15 encompasses water, saline, and buffers; and there are no other required elements in claims 6, 9 and 16.
Claim(s) 1, 6, 9, 15, 16 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun et al. J Cell Sci. (2013)126 (2): 520-53.
Claim 1 and claim 9: Sun et al disclose a trypanosomal vaccine, comprising: a flagellum adhesion protein 1 (FLA1) binding protein.
See Sun at p. 526 column 2 disclosing they have isolated a novel trypanosome flagellum adhesion protein 1 (FLA1) binding protein (FLA1BP). See p. 524 figure 4A.
See p. 523 figure 3A for “identification of a FLA1 binding protein, FLA1BP, by sequential coimmunoprecipitation (co-IP) and affinity purifications” and p. 523 column 1 disclosing cell lysates comprising FLA1BP, supernatant comprising FLA1BP and FLA1BP eluted by boiling – any of these correspond to a trypanosomal vaccine comprising a flagellum adhesion protein 1 binding protein and a pharmaceutical composition comprising said protein.
In addition, YFP::FLA1ΔC16R cells comprising flagellum adhesion protein 1 binding protein (approx.. 80 kDa) and YFP:FLA1BP cells correspond to the vaccine and pharmaceutical composition of claim 1. See p. 523 first paragraph column 1 and column 2 and figure 3.
Claim 6: the limitation that the vaccine is a Trypanosoma congolense vaccine is drawn to an intended use of the vaccine.
Claim 15 and claim 16: Sun et al disclose the composition comprising the trypanosomal vaccine comprises a pharmaceutically acceptable carrier. For instance, see cells expressing YFP::FLA1ΔC16R cells comprising flagellum adhesion protein 1 binding protein (approx.. 80 kDa) ( p. 523 first paragraph column 1 and column 2 and figure 3) in phosphate buffered saline containing glucose (see p. 530 under co-immunoprecipitation) which is a form adapted for mucosal (oral administration).
Claim 23: “means for administering the vaccine composition” is interpreted to mean a container. The vaccine composition as set forth above is necessarily in a container. Regarding, instructions, the content of printed matter will not distinguish the claimed product from the prior art. See MPEP 2112.01. Thus, the kit of claim 23 is anticipated by Sun et al.
Status of Claims
Claims 1-6, 9-16 and 23 are rejected. Claims 7-8, 17-18 and 21 are withdrawn from consideration.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLUWATOSIN A OGUNBIYI whose telephone number is (571)272-9939. The examiner can normally be reached IFP.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 5712720857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645