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 .
The amendment filed 4/28/26 has been entered.
Claims 24-38 have been added. Claims 2, 4, 7-9,19-20 and 22 have been cancelled. Claim 1, 3, 5, 10-11, 13-16, and 23 have been amended.
Claims 17, 18, 21 and 35-37are withdrawn. Claims 1,3, 5-6, 10-11, 12-16, 23-34 and 38 are under examination.
Claim Rejections Withdrawn
The rejection of claims 2-3 and 4-5 on the basis that it contains an improper Markush grouping of alternatives is withdrawn in view of the amendment to the claims.
The rejection of claims 2,4 and 9 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of the cancellation of the claims.
The rejection of claims 2,4 and 9 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in view of the cancellation of the claims.
The rejection of claim 9 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn in view of the cancellation of the claim.
The rejection of claims 2,4 and 9 under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more is withdrawn in view of the cancellation of the claims.
The rejection of claims 2, 4 and 9 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generated by distinct evolutionary mechanisms in African trypanosome species; PNAS 109(9):3416- 3421; cited in IDS) is withdrawn in view of the cancellation of the claims.
The rejection of claim 1, 6, 9, 15, 16 and 23 under 35 U.S.C. 102(a)(1) as being anticipated by Sun et al. J Cell Sci. (2013)126 (2): 520-53 is withdrawn in view of the amendment to the claims.
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, 3, 5-6, 10-16, 23-34 and 38 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 flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, wherein said trypanosomal vaccine can elicit a protective immune response.
New claim 24 is drawn to a trypanosomal vaccine comprising: a nucleic acid encoding a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, wherein said trypanosomal vaccine can elicit a protective immune response.
The genus of FLA1 binding proteins comprises 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;
In addition, the specification vaccine composition encompass a genus of compositions of the FLA1 protein or nucleic acid encoding the protein wherein members of the genus of compositions comprise with different diluents, carriers, other saponin adjuvants, or excipients.
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 FLA1 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 FLA1 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 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.
With respect to the respective genus (i.e. for each of FLA1 binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 and FLA1 binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 3) of nucleic acid sequences encoding the FLA1 binding protein, the genus comprises different nucleic acid (including DNA or mRNA or cDNA) sequences with differing structure. The specification does not disclose the commons structure of each genus that elicits a protective immune response. The specification does not disclose that nucleic acid sequences are able to elicit immune responses. While the nucleic acid encodes the protein, nucleic acids are not normally regarded as being immunogenic unless they have pathogen associated molecular patterns (PAMP) e.g. CpG. See Hartmann et al. Advances in Immunology. Volume 133, 2017, pages 121-169 – see whole paper especially figure 2. The specification does not teach that the nucleic acid sequences have such PAMP that can elicit a protective immune response.
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.
Applicant’s Remarks
Applicant’s state that independent claim 1 recites that the binding protein comprises an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 and that the trypanosomal vaccine can elicit a protective immune response in a mammal and that the current claims are limited to FLA1 binding proteins comprising the amino acid sequences of SEQ ID NOs: 1 and 3 as well as nucleic acids encoding therefor, Applicant respectfully submits that the current claim scope is fully supported by the application as filed, which demonstrates the ability of vaccines comprising these proteins to provide protection against infection (see, e.g., Examples 2-4 of the application as filed)
Applicant notes that SEQ ID NO: 1 is the ectodomain of TelL3000_0_17090 and SEQ ID NO: 3 is the ectodomain of TeIL3000_0_35140 as referred to in the examples. Applicant submits that this description has been acknowledged by the Examiner as being described and enabled. See, e.g., page 12 of the Office Action.
Response
Applicant’s argument has been carefully considered but is not found persuasive. This is because claim 1 and 24 states:
a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3.
This is contrary to Applicant’s argument that the claim has been amended to now recite a flagellum adhesion protein 1 (FLA1) binding protein comprising the amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3.
As stated in the rejection above, a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 encompasses a flagellum adhesion protein 1 (FLA1) binding protein comprising fragment of SEQ ID NO: 1 or 3.
Thus, the claim 1 and dependent claims are drawn to a genus of FLA1 proteins comprising species which are variants of SEQ ID NO: 1 and claim 1 and dependent claims are drawn to a genus of FLA1 proteins comprising species which are variants of SEQ ID NO: 3.
Claim 24 and dependent claims are drawn to a genus of nucleic acid sequences encoding FLA1 proteins comprising species which encode variants of SEQ ID NO: 1 and claim 24 and dependent claims are drawn to a genus of nucleic acid sequences encoding FLA1 proteins comprising species which encode variants of SEQ ID NO: 3.
The specification does not disclose the common structure of members of the genus of variants of SEQ ID NO: 1 and the common structure of members of the genus of variants of SEQ ID NO: 3 that correlates with the function as a vaccine that elicit a protective immune response.
The claim also encompass the genus described above in combination with different diluent, carrier or adjuvants.
The only adjuvant described that in combination with an FLA1 binding protein comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 1 and SEQ ID NO: 3 and elicited a protective immune response was Quil A adjuvant. No other adjuvant or carrier or diluent was described as of the effective filing date that could be combined with the FLA1 binding proteins to elicit a protective immune response.
The specification teaches that:
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 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 and the respective nucleic acid encoding sequences that confers protection with or without adjuvant from Trypanosoma infection.
With respect to the respective genus (i.e. for each of FLA1 binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 and FLA1 binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 3) of nucleic acid sequences encoding the FLA1 binding protein, the genus comprises different nucleic acid (including DNA or RNA or cDNA) sequences with differing structure. The specification does not disclose the commons structure of each genus that elicits a protective immune response. The specification does not disclose that the nucleic acid sequences encoding the FLA1 protein are able to elicit immune responses.
In light of the considerations set forth in the rejection, the claims do not comply with the written description requirement.
Claim Rejections - 35 USC § 112 – Scope of enablement
The rejection of claims 1, 3, 5-6, 10-16 and 23 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 that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID NO: 1 with QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria) and is enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID SEQ ID NO: 3 with QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria);
the specification, is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID NO: 1 without QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria) and is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID SEQ ID NO: 3 without QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria) and;
the specification is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising an amino acid sequence set forth in SEQ ID NO: 1 and is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising an amino acid sequence set forth in SEQ ID NO: 1 SEQ ID NO: 3 with or without QUIL A 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 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 comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, wherein said trypanosomal vaccine an elicit a protective immune response.
The breadth of the claims encompasses variant FLA1 binding protein sequences The claims require the function of a trypanosomal vaccine eliciting a protective immune response.
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;
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 with or without adjuvant with eliciting a protective immune response.
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 that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID NO: 1 with QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria) and is enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID SEQ ID NO: 3 with QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria).
The specification, is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID NO: 1 without QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria) and is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising the amino acid sequence set forth in SEQ ID SEQ ID NO: 3 without QUIL A (saponin adjuvant derived from bark of Quillaja Saponaria).
The specification is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising an amino acid sequence set forth in SEQ ID NO: 1 and is not enabling for a Trypanosomal vaccine that elicits a protective immune response, the vaccine comprising an amino acid sequence set forth in SEQ ID NO: 1 SEQ ID NO: 3 with or without QUIL A adjuvant.
Applicant’s Remarks
Applicant’s state that independent claim 1 recites that the binding protein comprises an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 and that the trypanosomal vaccine can elicit a protective immune response in a mammal and that the current claims are limited to FLA1 binding proteins comprising the amino acid sequences of SEQ ID NOs: 1 and 3 as well as nucleic acids encoding therefor, Applicant respectfully submits that the current claim scope is fully supported by the application as filed, which demonstrates the ability of vaccines comprising these proteins to provide protection against infection (see, e.g., Examples 2-4 of the application as filed)
Applicant notes that SEQ ID NO: 1 is the ectodomain of TelL3000_0_17090 and SEQ ID NO: 3 is the ectodomain of TeIL3000_0_35140 as referred to in the examples. Applicant submits that this description has been acknowledged by the Examiner as being described and enabled. See, e.g., page 12 of the Office Action.
Response
Applicant’s argument has been carefully considered but is not found persuasive. This is because claim 1 states that:
a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3.
This is contrary to Applicant’s argument that the claim has been amended to now recite a flagellum adhesion protein 1 (FLA1) binding protein comprising the amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3.
As stated in the rejection above, a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3 encompasses a flagellum adhesion protein 1 (FLA1) binding protein comprising a fragment of SEQ ID NO: 1 or 3.
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 with or without adjuvant with eliciting a protective immune response.
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.
For these reasons and for those set forth in the rejection, the rejection is maintained.
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, 3, 5-6, 10-12, 15, 16, 23-30, 33, 34 and 38 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Claim 1 is drawn to a trypanosomal vaccine comprising a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, wherein said trypanosomal vaccine can elicit a protective immune response.
New claim 24 is drawn to a trypanosomal vaccine comprising: a nucleic acid encoding a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, wherein said trypanosomal vaccine can elicit a protective immune response.
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.
The composition furthers comprises an invariant flagellum antigen or nucleic acid sequence encoding invariant flagellum antigen. This is also a product of nature the antigen is from T. vivax (see paragraph 67) and is encoded by the genome. 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 or nucleic acid sequence on their own are product of nature and there is no evidence that the combination of proteins or combination of nucleic acids react together resulting in something "markedly different”. The composition is thus a nature-based composition that is not “markedly different” as each antigen or each nuclei acid sequence continues to behave as it normally would.
Thus, the claims are drawn to are products of nature without significantly more.
As per claim 15 and claim 33, pharmaceutically acceptable carrier, diluent or excipient encompasses liquid such as milk or water. The combination of milk or water and the protein or nucleic acid sequence 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 or nucleic acid sequence 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 and claim 34, the combination of the binding protein or nucleic acid sequence and milk/water is a liquid and thus is adapted for parenteral administration, epidural administration and mucosal administration. Essentially, claim 16 an claim 34 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.
The claims 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 composition to a subject and not merely an intended use of the composition or by reciting functional limitations such as eliciting a protective immune response. See MPEP 2106.04(d)(2).
STEP 2B – THE CLAIMS DO NOT AMOUNT TO SIGNIFICANTLY MORE. SEE MPEP 2106.05.
Claim 23 and claim 38 is drawn to a kit of parts comprising the vaccine composition of claim 1 or the vaccine of claim 24 respectively, 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 or nucleic acid encoding the FLA1 remains the same despite presence of instructions that are not functionally related. Thus, claim 23 and 38 do 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.
Response to Applicant’s Argument
Applicants argue that the current claims directed to a trypanosomal vaccine which can elicit a protective immune response thus amounts to a practical application and significantly more. This practical application is the provision of the prophylaxis of trypanosomal infection by the vaccine.
Applicants argument has been carefully considered but is not persuasive. The claims 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 vaccine composition to a subject and not merely an intended use of the composition or by reciting functional limitations such as “eliciting a protective immune response”. See MPEP 2106.04(d)(2).
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, 6, 15,16, 24, 27, 33 and 34 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, 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 and claim 33 encompasses water, saline, and buffers; and there are no other required elements in claims 6, 16, 27 and 34.
Applicant’s Argument
Applicant submits that the Office acknowledges that none of the prior art disclose a trypanosomal vaccine as currently claimed, namely Therefore, the objections appear to be based on the alleged disclosures in the prior art of merely FLA1 binding protein sequences with homology to SEQ ID NOs: 1 and 3. As such, the currently presented claim amendments which, in addition to the previously clear statement in the preamble that the current invention is drawn to a trypanosomal vaccine, now recite that the inventive vaccine can elicit a protective immune response in a mammal. The claimed feature of being a vaccine able to elicit an immune response is neither taught nor suggested in the Office's cited art.
Response
Applicants argument has been carefully considered but is not found persuasive. The recitation of “trypanosomal vaccine” and “eliciting a protective immune response in a mammal” is drawn to an intended use.
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.
In addition, the claims do not recite that the FLA1 binding protein is isolated or the nucleic acid encoding the FLA1 binding protein is isolated, thus claim 1 and claim 24 also reads on the T. congolense IL3000 parasite whose genome, a nucleic acid sequence encodes FLA1 and the parasite also comprises FLA1. Trypanosoma congolense strain IL3000 comprises genome that encodes a protein that is 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.
New Claim Rejection Based on Amendment
Claims 24-34 and 38 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use 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 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 a nucleic acid sequence encoding a flagellum adhesion protein 1 (FLA1) binding protein comprising an amino acid sequence as set forth in SEQ ID NO: 1 or SEQ ID NO: 3, wherein said trypanosomal vaccine an elicit a protective immune response.
The breadth of the claims encompasses different types of nucleic acid sequences that can encode the FLA1 such as DNA, mRNA and cDNA. The claims require the function of a trypanosomal vaccine eliciting a protective immune response. In addition, there is variability because the nucleic acid sequences encode variant FLA1.
This is because 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;
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 regarding vaccines comprising nucleic acid sequences that encode the FLA1 protein or variants thereof, the specification does not correlate any immunogenic response elicited by nucleic acid sequences encoding SEQ ID NO: 1 or 3 or other variants thereof with or without adjuvant and elicit a protective immune response.
The specification does not disclose that nucleic acid sequences are able to elicit immune responses. While nucleic acid sequences encodes protein, nucleic acids are not normally regarded as being immunogenic unless they have pathogen associated molecular patterns (PAMP) e.g. CpG. See Hartmann et al. Advances in Immunology. Volume 133, 2017, pages 121-169 – see whole paper especially figure 2. The specification does not teach that the nucleic acid sequences encoding FLA1 or variants of FLA1 have such PAMP that can elicit a protective immune response.
The specification also does not correlate the immune response generated with the nucleic acid sequences encoding the FLA1 binding proteins with diluents, carriers, other saponin adjuvants, or excipient having similar results seen for TcIL3000_0_35140 or TcIL3000_0_17090 with QUIL A adjuvant via subcutaneous administration.
No immune response generated by said nucleic acid sequences with or without adjuvant is disclosed that correlates with protective immune response.
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.
Status of Claims
Claims 1, 3, 5-6, 10-16, 23-34 and 38 are rejected. Claims 17-18, 21 and 35-37 are withdrawn from consideration.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to 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, Michael Allen can be reached at 5712703497. 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
Prosecution Insights