The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1-23-2026 has been entered.
The amendment filed on 1-26-2026 is acknowledged. Claims 1, 15, 37 and 44 have been amended. Claims 7-8 and 44 have been canceled. Claims 1, 6, 9-12, 14, 15, 23, 29, 30, 32-37, 43 and 43-45 are pending. Claims 10-12, 14-15, 23, 32-37 and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 6, 9, 29, 30 and 45-46 are currently under examination.
Claim Rejections Withdrawn
The new matter rejection of claims 1, 6-9, 29, 30 and 43-46 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description requirement based on the recitation of the phrase “…at an epitope site designated as Xn in SEQ ID NO:4…” is withdrawn in light of the amendment thereto.
The rejection of claim 1 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being rendered vague and indefinite by the use of the phrase “… the heterologous epitope is inserted at an epitope site…” is withdrawn in light of the amendment thereto.
The rejection of claims 1, 7-9, 29-30 and 43 under 35 U.S.C. 102(a)(1) as being anticipated by Martinez-Becerra et al. (Infection and Immunity Vol. 81 No. 12, pages 4470-4477 – IDS filed on 4-13-2022) is withdrawn in light of the amendment thereto.
New Grounds of Rejection
35 USC § 112
Written Description
Claims 1, 6, 29 and 30 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.
The rejected claim are drawn to fusion proteins comprising a backbone with at least 95% sequence identity to SEQ ID NO:4 and at least one heterologous epitope from each of IpaB, VirG, GuaB, StxA, Stx2A, and StxB Shigella virulence factors. The specification discloses heterologous epitopes with the amino acid sequence of SEQ ID NO:10, 12, 16, 18, 20 or 22. These heterologous epitopes meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. However, the instant claims are drawn to an epitope of a IpaB, VirG, GuaB, StxA, Stx2A, and StxB Shigella virulence factor (undefined sequence) from any and all Shigella species. None of these “heterologous epitopes” meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph since the specification is silent as to what constitutes an "epitope” or what characteristics said epitope must possess.
To fulfill the written description requirements set forth under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. To adequately describe the genus of fusion proteins, Applicant must adequately describe the heterologous epitopes derived from the IpaB, VirG, GuaB, StxA, Stx2A, and StxB virulence factors of a given Shigella species. The term “epitope” is a variable term depending on the components of the immune system with which it is “interacting”. There are three types of epitopes: conformational, linear, and discontinuous wherein conformational epitopes are formed through the interaction of amino acid residues which are disconnected from each other. The number of conformational epitopes is unknown. Linear epitopes are determined not just by their primary structure (sequence of amino acids) but also by other residues present. More distant amino acid residues of the antigen as well as those which flank the primary structure affect the linear epitope’s three-dimensional conformation. Discontinuous epitopes consist of parts of the protein which are brought together by protein folding rather than being close to each other in the structure. This class of epitope can contain both conformational and linear parts. Data from various studies have provided evidence that most antigen-antibody binding occurs at discontinuous epitope sites. Protective antibodies (for example, those in vaccines) particularly rely on this. Additionally, T- and B- cells provide an immunologic response based on pathogen-specific memory. B-cell epitopes are the portion of the antigen that antibodies or immunoglobulin binds to. T-cell epitopes are found on the surface of an antigen-presenting cell and are bound to major histocompatibility complex molecules. Given, that the specification is silent with regard to what constitutes an “epitope” in the context of their invention and is limited to describing 7 “epitopes” derived from the a Shigella virulence factor. SEQ ID NO:10 and SEQ ID NO:12 represent portions of the IpaB protein of Shigella flexneri, SEQ ID NO:16 represents a portion of the VirG protein of Shigella flexneri, SEQ ID NO:18 represents a portion of the StixA protein of Shigella flexneri, SEQ ID NO:20 represents a portion of the GuaB protein of Shigella flexneri, SEQ ID NO:22 represents a portion of the Stx2 protein of Shigella flexneri and SEQ ID NO:24 represents a portion of the StxB protein of Shigella flexneri. Consequently, the specification, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of antibodies. The specification fails to disclose what constitutes an “epitope” or the characteristics said epitope must possess. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of “heterologous epitopes” to which the claims refer; and accordingly, the specification fails to adequately describe at least a substantial number of members of the claimed genus of fusion proteins.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the 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. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"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 re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”
And:
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
Therefore, because the art is unpredictable, in accordance with the MPEP, only the heterologous epitopes with the amino acid sequence of SEQ ID NO: 10, 12, 16, 18, 20, 22 or 24, but not the full breadth of the claims meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6, 9, 29, 30 and 45-46 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is rendered vague and indefinite by the use of the phrase The rejection of claim 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being rendered vague and indefinite by the use of the phrase “…epitope of each of IpaB, VirG, GuaB, StxA, Stx2A, and StxB Shigella virulence factors.” is withdrawn. It is unclear what is meant to be engendered by said phrase as the terms IpaB, VirG, GuaB, StxA, Stx2A, and StxB convey no particular structure. Moreover, the term “epitope” is a variable term depending on the components of the immune system with which it is “interacting”. There are three types of epitopes: conformational, linear, and discontinuous wherein conformational epitopes are formed through the interaction of amino acid residues which are disconnected from each other. The number of conformational epitopes is unknown. Linear epitopes are determined not just by their primary structure (sequence of amino acids) but also by other residues present. More distant amino acid residues of the antigen as well as those which flank the primary structure affect the linear epitope’s three-dimensional conformation. Discontinuous epitopes consist of parts of the protein which are brought together by protein folding rather than being close to each other in the structure. This class of epitope can contain both conformational and linear parts. Data from various studies have provided evidence that most antigen-antibody binding occurs at discontinuous epitope sites. Protective antibodies (for example, those in vaccines) particularly rely on this. Additionally, T- and B- cells provide an immunologic response based on pathogen-specific memory. B-cell epitopes are the portion of the antigen that antibodies or immunoglobulin binds to. T-cell epitopes are found on the surface of an antigen-presenting cell and are bound to major histocompatibility complex molecules. Given, that the specification is silent with regard to what constitutes an “epitope” in the context of their invention and is limited to describing 7 “epitopes” derived from IpaB, VirG, GuaB, StxA, Stx2A, and StxB Shigella virulence factors, it is impossible to determine the metes and bounds of the claimed invention.
Claim 9 is rendered vague and indefinite by the use of the phrase “the at least one heterologous epitope comprises one or more of SEQ ID Nos: 10, 12, 16, 18, 20, 22 and 24.”. It is unclear what is meant to be engendered by said phrase as a SEQ ID NO: constitutes an abstraction representing a given amino acid sequence or nucleic acid sequence. Moreover, it is unclear whether said phrase is referring to a single heterologous epitope comprising one or more of the sequences represented by the recited SEQ ID NOs or a multiplicity of heterologous epitopes wherein each epitope has a sequence of one of the recited SEQ ID NOs. As written, it is impossible to determine the metes and bounds of the claimed invention.
Claim 45 recites the limitation "comprising each of: an IpaD epitope comprising SEQ ID NO: 6, an IpaD epitope comprising SEQ ID NO: 8, an IpaB epitope comprising SEQ ID NO: 10, an IpaB epitope comprising SEQ ID NO: 12, an IpaD epitope comprising SEQ ID NO: 14, a VirG epitope comprising SEQ ID NO: 16, a StxA epitope comprising SEQ ID NO: 18, a GuaB epitope comprising SEQ ID NO: 20, a Stx2A epitope comprising SEQ ID NO: 22, and a StxB epitope comprising SEQ ID NO: 24" in lines 1-6. There is insufficient antecedent basis for this limitation in the claim. The claimed fusion protein contains epitopes from Shigella virulence factors IpaD, IpaB, VirG, GuaB, StxA, Stx2A, and StxB whereas the independent claim is limited to epitopes from IpaB, VirG, GuaB, StxA, Stx2A, and StxB.
Claim 46 recites the limitation " comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 2, or wherein the fusion protein comprises SEQ ID NO: 2" in lines 1-3. There is insufficient antecedent basis for this limitation in the claim. The polypeptide of SEQ ID NO:2 contains epitopes from Shigella virulence factors IpaD, IpaB, VirG, GuaB, StxA, Stx2A, and StxB whereas the independent claim is limited to epitopes from IpaB, VirG, GuaB, StxA, Stx2A, and StxB.
Conclusion
No claim is allowed.
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/ROBERT A ZEMAN/Primary Examiner, Art Unit 1645 July 23, 2026
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