DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the claims
Claims 1-3, 5, 7-10, 13, 15-17, 21, 23, 26-27 and 30-32 are pending and examined.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5, 7-10, 13, 15-17, 21, 23, 26-27 and 30-32 remain 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.
The claims are drawn to a method of treating or preventing a cancer in a subject,
said method comprising: administering to the subject at least one immunogenic peptide,
a nucleotide sequence that expresses the immunogenic peptide, or combinations thereof, wherein the immunogenic peptide is expressed by one or more chimeric nucleotide sequences derived from cells associated with the cancer, wherein the cells associated with the cancer comprise cancer cells and cells near the cancer cells, wherein the one or more chimeric nucleotide sequences have a higher prevalence in cancer cells when compared to non-cancer cells, wherein the immunogenic peptide comprises a neoantigenic region, and wherein the immunogenic peptide elicits an immune response against cells associated with the cancer.
With regard to the independent claim 1, for a method of treatment, it unclear if the “subject” represents the general population of organisms at large or is it a subject in need of treatment or prevention.
In the amendment filed on 08/17/2026, Applicant argued that: “Applicants respectfully submit that the term "subject" has sufficient definiteness to clearly represent different populations of organisms with different needs of treatment. For instance, dependent claim 23 exemplifies that the subject can be a human being suffering from or vulnerable
to a cancer.”
The arguments were carefully considered but not found persuasive because, if Applicant desires to perform the method on a certain group of “subjects” in need of the treatment, it should be stated as such in the claim.
Further, the claim uses the term “cells associated with the cancer comprise cancer cells and cells near the cancer cells” without indicated what the limits of the term “near” is. Are the cells “near” the cancer cells cancerous too?
Also, the “prevalence” of the nucleotide sequences is it before or after administration of the nucleotide sequences.
Is the immune response elicited against the cells near the cancer cells too, since, according to the description of the cells associated with the cancer, non-cancerous cells would also be affected by the immunological response?
Further, the method claimed is considered as incomplete for omitting essential elements, such omission amounting to a gap between the elements. The omitted elements are: The dosage, administration regimen, length of treatment and metrics to assess the effectiveness of the treatment.
On page 8 of the Remarks, Applicant argues that: “… the Office Action has not provided any explanation for why the aforementioned elements represent "essential elements." “.
The arguments were carefully considered but not found persuasive because, for any method of treatment, in order to put the Invention in the hands of the public, the dosage of the treating agent, the regimen of administration, length of treatment and metrics to assess the effectiveness of the treatment needs to be disclosed. Otherwise, the “method” is akin to stating: “you are sick; take some medication”.
As such the metes and bounds of the claims cannot be determined.
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, 8-9, 13, 15-17, 21, 23, 26, 27 and 30-32 remain and claims 3, 5, 7, 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a method of treating or preventing a cancer in a subject,
said method comprising: administering to the subject at least one immunogenic peptide,
a nucleotide sequence that expresses the immunogenic peptide, or combinations thereof, wherein the immunogenic peptide is expressed by one or more chimeric nucleotide sequences derived from cells associated with the cancer, wherein the cells associated with the cancer comprise cancer cells and cells near the cancer cells, wherein the one or more chimeric nucleotide sequences have a higher prevalence in cancer cells when compared to non-cancer cells, wherein the immunogenic peptide comprises a neoantigenic region, and wherein the immunogenic peptide elicits an immune response against cells associated with the cancer. A group of 20 hexa to deca peptides (SEQ ID NOs: 1-20) (and also derivatives thereof, analogs thereof, homologs thereof) are indicated as immunogenic peptides to be used in breast cancer according to claim 2.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). (emphasis added). See also MPEP 2163.04.
The specification discloses that Applicant's objective was to find recurrent fusion transcripts that have the potential to generate candidate neoantigens presented by major histocompatibility complex class I (MHC I) during breast cancer progression. Applicant found 18 neoantigen peptides predicted to be presented by 1-6 MHC class I alleles with a binding affinity of IC50<50 nM and 1-15 MHC class I alleles with a binding affinity of IC50<500 nM. Next, the immunogenic peptides were further screened for effectiveness as vaccine candidates in accordance with the scheme illustrated in FIG. 7. First, an in vitro Enzyme-Linked Immunospot (ELISpot) assay was established where the CD8 T cell responses were assessed after a long-term culture of peripheral blood mononuclear cells (PBMCs) from an HLA-matched healthy donor. The response was assessed through the enumeration of antigen specific IFN-γ secreting T cells. (Example I). Next Applicant illustrates an mRNA design for chimeric fusion protein candidates modeled after a eukaryotic mRNA template. Peptide cassettes were designed to include neoantigenic regions of proteins derived from chimeric RNAs, with 5′- and 3′-region cassettes and spacers on each side experimentally determined by in-vitro expression. (example 2). From here Applicant concludes that: “… it is believed that one skilled in the art can, using the description herein, utilize the present disclosure to its fullest extent. The embodiments described herein are to be construed as illustrative and not as constraining the remainder of the disclosure in any way whatsoever. While the embodiments have been shown and described, many variations and modifications thereof can be made by one skilled in the art without departing from the spirit and teachings of the invention. Accordingly, the scope of protection is not limited by the description set out above, but is only limited by the claims, including all equivalents of the subject matter of the claims. The disclosures of all patents, patent applications and publications cited herein are hereby incorporated herein by reference, to the extent that they provide procedural or other details consistent with and supplementary to those set forth herein.” ([0092]). This represents the extent of the guidance and working examples of the Specification. As such, the Specification actually describes the detection and construction of potential reagents that might be tested for treating or preventing breast cancer and this represents what actually Applicant was in possession of.
There is no actual disclosure of any administration regimens, no actual dosages or positive steps in the "method" claimed. The claims are indicating is a theoretical hypothesis without any experimental backing and thus the invention would not be put in the possession of the public but only after the completion of this incompletely described research project. The first paragraph of 35 U.S.C. 112 requires that the "specification shall contain a written description of the invention * * *." This requirement is separate and distinct from the enablement requirement. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111, 1114 (Fed. Cir. 1991). See also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim's enablement is not equally conclusive of that claim's satisfactory written description"). The written description requirement has several policy objectives. "[T]he 'essential goal' of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to put the public in possession of what the applicant claims as the invention. See Regents of the University of California v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). *>"The 'written
description' requirement implements the principle that a patent must describe the
technology that is sought to be patented; the requirement serves both to satisfy the
inventor's obligation to disclose the technologic knowledge upon which the patent is
based, and to demonstrate that the patentee was in possession of the invention that is
claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir.
2005). Further, the written description requirement promotes the progress of the useful
arts by ensuring that patentees adequately describe their inventions in their patent
specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent's term. A specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose (Cooper v. Goldfarb, 154 F.3d 1321 , 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998)). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) ("[T]here cannot be a reduction to practice of the invention*** without a physical embodiment which includes all limitations of the claim. "); Estee Lauder Inc. v. L'Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) ("[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose."); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
Further analysis will address the reagents to be wishfully used in the method claimed.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
In the instant case, the specification discloses detection of Applicant found, in breast cancer samples, 18 neoantigen peptides predicted to be presented by 1-6 MHC class I alleles with a binding affinity of IC50<50 nM and 1-15 MHC class I alleles with a binding affinity of IC50<500 nM. However, what is claimed is much broader: the use of any immunogenic peptide that elicits an immune response against cells associated with
the cancer, and derivatives, analogs, homologs thereof. There is no indication where the mutations (up 20% of the length of the peptide) would be performed, or where the long list of “one or more amino acid moieties derivatized with one or more functional groups, wherein the one or more functional groups are positioned on amino acid backbones, R groups, or combinations thereof, and wherein the one or more functional groups are selected from the group consisting of alkanes, alkenes, ethers, alkynes, alkoxyls, aldehydes, carboxyls, hydroxyls, hydrogens, sulfurs, phenyls, cyclic rings, aromatic rings, heterocyclic rings, linkers, or combinations thereof” are to be present in the immunogenic peptide. Such a broadly defined immunogenic peptide would necessarily entail a huge number of compounds for which the 18 neoantigen peptides actually disclosed would not constitute a representative number of species. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera. Again, the inescapable conclusion is that Applicant was not in possession of the full scope of the subject matter claimed.
Claims 1-3, 5, 7-10, 13, 15-17, 21, 23, 26-27 and 30-32 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 claims 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 use the invention.
The claims are drawn to a method of treating or preventing a cancer in a subject,
said method comprising: administering to the subject at least one immunogenic peptide,
a nucleotide sequence that expresses the immunogenic peptide, or combinations thereof, wherein the immunogenic peptide is expressed by one or more chimeric nucleotide sequences derived from cells associated with the cancer, wherein the cells associated with the cancer comprise cancer cells and cells near the cancer cells, wherein the one or more chimeric nucleotide sequences have a higher prevalence in cancer cells when compared to non-cancer cells, wherein the immunogenic peptide comprises a neoantigenic region, and wherein the immunogenic peptide elicits an immune response against cells associated with the cancer. A group of 20 hexa to deca peptides (SEQ ID NOs: 1-20) (and also derivatives thereof, analogs thereof, homologs thereof) are indicated as immunogenic peptides to be used in breast cancer according to claim 2.
As indicated supra there is no method of treating or prevention of cancer in general by using the immunogenic peptides (or derivatives, etc) indicated. The immunogenic peptides were screened in vitro for effectiveness as vaccine candidates. There is no indication of an in vivo testing for assessment of the effectiveness for treatment or prevention. Each reagent needs to be thoroughly tested for its use in vivo, and these tests are, according to the art, time and resources consuming. A series of factors need to be considered, for instance the route of administration, the dosages the administration regimens since there is no a priori known how the regents would react in an in vivo environment. Further, given the fact that the claims are not restricted to a reasonable number of compounds (nota bene, claim 2 recites the potential use of 20 peptides, each comprising “one or more amino acid moieties derivatized with one or more functional groups, wherein the one or more functional groups are positioned on amino acid backbones, R groups, or combinations thereof, and wherein the one or more functional groups are selected from the group consisting of alkanes, alkenes, ethers, alkynes, alkoxyls, aldehydes, carboxyls, hydroxyls, hydrogens, sulfurs, phenyls, cyclic rings, aromatic rings, heterocyclic rings, linkers, or combinations thereof”). Given the fact that the art is not aware of the use of the 20 compounds claimed in claim 2 for treating or preventing any cancer, the experimentation would proceed with unpredictable results. For a person of ordinary skill in the art to actually put in practice the idea claimed would necessitate a vast amount of experimentation with uncertain outcomes, amount of experimentation that is considered undue.
If Applicants are in possession of experimental data which would show that the
method as claimed was actually used they are strongly encouraged to present the data for critical examination.
Claim Rejections - 35 USC § 102
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.
Claim 1 remains rejected under 35 U.S.C. 102(a)(1) as being anticipate by Artomov (cited previously).
As indicated in the previous Office action, the reference disclosed a method of selecting a therapeutic fusion-specific vaccine for a cancer patient, the method comprising: a) determining the presence of one or more tumor-specific gene fusions in a biological sample from the cancer patient; b) obtaining information relating to one or more HLA alleles of the cancer patient; c) analyzing a library of fusion-specific vaccines, wherein each fusion specific vaccine in the library comprises one or more fusion-derived neoantigens having a nucleic acid sequence and/or an amino acid sequence corresponding to one or more tumor-specific gene fusions; and d) selecting at least one fusion specific vaccine in the library as the therapeutic fusion specific vaccine for the cancer patient by selecting the fusion-specific vaccine comprising one or more fusion-derived neoantigens that i) correspond to one or more tumor-specific gene fusions of the cancer patient, and ii) bind one or more HLA alleles of the cancer patient (claims). This method claimed was validated in Example 9: two most frequent types of the EWSR1 /FLl1 fusion, which is found in Ewing's sarcoma, occur due to junction of exon 7 of the EWSR1 gene with exon 5 or exon 6 of the FLU gene; fusion-derived peptides having 8-10 amino acids corresponding to the fusion junction were used for predicting peptide binding to MHC class I proteins (see Table 10).
On page 10 of the Remarks Applicant argues that: “Artomov fails to teach or suggest any methods of treating or preventing cancer by immunogenic peptides expressed by one or more chimeric nucleotide sequences derived from cells associated with cancer, where the chimeric nucleotide sequences have a higher prevalence in cancer cells when compared to the cells near the cancer cells.”
The arguments were carefully considered but not found persuasive because the
reference teaches determining the presence of one or more tumor-specific gene fusions in a biological sample from the cancer patient. The notion of specificity is conferred by the fact that the gene fusion in the tumor is not present or faintly present in adjacent cells.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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