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 .
Application Status
The amended claims filed October 6, 2023 are acknowledged. Claims 17, 19-34, and 36-37 are canceled. Claims 3, 12, and 16 are amended. Claims 1-16, 18, 35, and 38 are pending and under examination herein.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency – The vhCDR2 sequence of SEQ ID NO: 6, as recited in Figure 23 and in the CRF Sequence Listing, is “IWTGGST”. As such, SEQ ID NO: 6 and SEQ ID NO: 3 (another vhCDR2) share 100% sequence identity. However, the corresponding heavy chain v.2 (comprising SEQ ID NO: 5) for the vhCDR2 of SEQ ID NO: 6 in Figure 23 appears to denote that the vhCDR2 sequence should instead recite “IWAGGST”. As filed, the heavy chain sequence corresponding to SEQ ID NO: 5, as filed in the CRF Sequence Listing, contains an alanine (A) at the indicated residue.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
o A statement that identifies the location of all additions, deletions, or replacements of sequence information in the replacement “Sequence Listing XML” as required by 1.835(b)(3);
o A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4),
o A statement that the replacement "Sequence Listing XML" includes no new matter in accordance with 1.835(b)(5), and
o A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See pages 9-10 (¶ 0051) and page 31 (¶ 00140). 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.
The disclosure is further objected to for the following informalities:
¶ 0012, 0015-0016, and 0019 refer to individual claims (e.g., “claim 8”, “any one of claims 1 to 11”, “any one of claims 1 to 12”, “claim 14”). It is unclear if the language of these passages was intended to refer to specific claim numbers.
The Brief Description of the Drawings contains references to color (e.g., “red”, “blue”, “green”) throughout. Since the Drawings are in black/white, references to color should be omitted.
The description for Figure 20A states that “anti-IL7R antibody used for in vivo treatment (in Figure 7) does not bind to the ligand binding site of IL7R”, but the figure itself has text stating “(Ab binds to IL7 binding site)”. Further, the description for Figure 24A states that “anti-IL7R antibody used for in vivo treatment (in Figure 7) does not bind to the ligand binding site of IL7R” and similarly shows text stating “(Ab binds to IL7 binding site)”. In each of Figures 20A and 24A, it appears that representative extracellular flow cytometry staining is shown for two antibodies, but the description for Figure 7 states that a single antibody was used in the method of treatment.
There is inconsistency among the specification (e.g., page 23, ¶ 00106-00108), Figure 23, and the claims with respect to whether SEQ ID NO: 1, 5, and 7 (which are each 118 residues in length) correspond to a heavy chain variable domain or to a full-length heavy chain, and whether SEQ ID NO: 8 (which is 108 residues in length) corresponds to a light chain variable domain or a full-length light chain. Full-length immunoglobulin heavy chains comprise a variable domain (VH) and three constant domains (CH1, CH2, CH3), and full-length immunoglobulin light chains comprise a variable domain (VL) and constant domain (CL). Janeway (Chapter 3, Immunobiology: The Immune System in Health and Disease (5E). (2001) New York: Garland Science) teaches that each variable domain and constant domain is approximately 110 amino acids in length.
Appropriate correction and/or clarification is required.
Drawings
The drawings are objected to because Figure 23 indicates that the underlined amino acid sequence of “IWAGGST” in heavy chain v.2 (according to IMGT numbering) should correspond to the second CDR, but the recited vhCDR2 sequence beneath the heavy chain sequence recites “IWTGGST” instead. In addition, the labeling in the figure appears to indicate that the amino acid sequences of SEQ ID NO: 1, 5, and 7 correspond to heavy chains, and that the amino acid sequence of SEQ ID NO: 8 corresponds to a light chain, but the figure description states that these are “variable heavy chains and variable light chains”, seemingly referring to the variable domain of a heavy chain or light chain. 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.
Claim Objections
Claims 7-8 and 10 are objected to because of the following informalities: The claims do not recite a conjunction (e.g., “and”, “or”) between the two components comprised in the antibody. Consider, e.g., line 4 of claims 7, claim 8, and claim 10, compared to, e.g., line 4 of claim 5, which contains “and”. Appropriate correction is required.
For the purpose of examining the claims on the merits, the Examiner is treating the claims as requiring both elements (“and”).
Claims 5-6 and 8-11 are objected to because there is inconsistency among the specification, Figure 23, and these claims with respect to whether SEQ ID NO: 1, 5, and 7 (which are each 118 residues in length) correspond to a heavy chain variable domain or to a full-length heavy chain, and whether SEQ ID NO: 8 (which is 108 residues in length) corresponds to a light chain variable domain or a full-length light chain. Full-length immunoglobulin heavy chains comprise a variable domain (VH) and three constant domains (CH1, CH2, CH3), and full-length immunoglobulin light chains comprise a variable domain (VL) and constant domain (CL). Janeway (Chapter 3, Immunobiology: The Immune System in Health and Disease (5E). (2001) New York: Garland Science) teaches that each variable domain and constant domain is approximately 110 amino acids in length. Based on the teachings of Janeway, a full-length heavy chain (VH+CH1+CH2+CH3) would be expected to have well above the 118 residues comprised in SEQ ID NO: 1, 5, and 7, and a full-length light chain (VL+CL) would be expected to have more than the 108 residues comprised in SEQ ID NO: 8.
Claim Rejections - 35 USC § 112(b)
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.
Claim 3 is 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 3 recites the composition of claim 1 (which comprises an antibody that specifically binds to IL-7R and does not prevent binding of IL-7R to IL-7), wherein the antibody binds to a ligand-binding site of IL-7R. Given that IL-7R binds to its ligand (IL-7) at a ligand-binding site, it is unclear how an antibody that binds to said ligand-binding site (thereby blocking other molecules, such as the IL-7 ligand, from binding to said ligand-binding site) would not prevent binding of IL-7R to IL-7.
Claim Rejections - 35 USC § 112(a)
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, 12-16, 35, 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.
“[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).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
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). “[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). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
Amgen Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367 (Fed. Cir. 2017) supported previous decisions (Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014)) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. Thus, claiming an antibody by describing the invention by what it does (function) rather than what it is (structure) is invalid. This can be overcome if a relevant number of species with structure/function correlation is known to the art or present in the specification.
The claimed invention. The nature and scope of the claimed invention at issue is a composition comprising an antibody that specifically binds to interleukin 7 receptor (IL7R), wherein the antibody does not prevent binding of IL7R to interleukin 7 (IL7), as set forth in claim 1 and its dependent claims. The claim does not satisfy the written description requirement because the claimed antibody is defined by specific functional language (“does not prevent binding of IL7R to IL7”) without reciting a corresponding defined structure that would be expected to correlate with this function. One of ordinary skill in the art cannot visualize or recognize all of the possible species of anti-IL7R antibodies that “prevent binding of IL7R to IL7” knowing only the antigen bound by said antibody. Claims 2-3, 12-16, and 35, which depend from claim 1, do not remedy these deficiencies of the claim.
Claim 2 further sets forth that the antibody does not bind to a ligand binding site of IL7R, while claim 3 further sets forth that the antibody does bind to a ligand binding site of IL7R. These claim limitations serve to define the claimed antibody by its epitope, again without reciting a corresponding structure expected to correlate with this specific function. Similarly, claim 12 is drawn to a composition comprising an antibody that competes with the antibody of claim 1 for binding to IL7R. The antibody comprised in the claimed composition is defined purely by functional language (i.e., binding to the same epitope as the antibody comprised in the composition of claim 1) without reciting a corresponding function that would be expected to correlate with this function. One of ordinary skill in the art cannot visualize or recognize all of the possible species of anti-IL7R antibodies that bind to these specific epitopes of IL7R knowing only the antigen bound by said antibody.
Further at issue, claim 38 recites a method of treating a patient with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) that comprises administering an anti-IL7R antibody that does not compete for binding with IL7. Similarly to the above, this limitation serves to define the antibody administered in the method by functional language without reciting a corresponding function that would be expected to correlate with this function.
State of the prior art. It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro (Frontiers in Immunology (2018) 8: 1751), “The IgG Molecule” (page 3) and Figure 1. Sela-Culang (Frontiers in Immunology (2013) 4: 302) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3).
Gershoni (Biodrugs (2007) 21(3): 145-156) teaches that antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (page 146, Section 1.1). The skilled artisan therefore understands that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence. Furthermore, the state of the art recognizes that it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements (e.g., linear and discontinuous epitopes) that are dictated by the unique interaction between an antibody and its cognate epitope (Blythe, Protein Science (2005) 14:246-248; page 246).
Exemplary antibodies that bind to IL-7R have previously disclosed in the art. By way of example, Jumaa-Weinacht (WO 2020/077190 A1) discloses compositions comprising a monoclonal antibody that binds to IL-7R for use in treating acute lymphoblastic leukemia, wherein the antibody inhibits IL-7 signaling in IL-7R Ph+ cells or binds to the extracellular domain of IL7R (e.g., Abstract; ¶ 0097-00109). Poirier (EP 3,423,496 B1) discloses humanized antibodies against the extracellular domain of the alpha chain of the receptor for IL-7 that do not interfere with the IL-7 or TSLP signaling pathways (e.g., Abstract). Durum (US 10,392,441 B2) discloses anti-IL-7Rα antibodies that specifically bind to the extracellular domain of IL-7Rα and use thereof in treating a subject with ALL (e.g., Abstract; Summary).
Scope of species disclosed in original specification. The methods section of the Examples recites that NSG mice injected with BCR-ABL-positive ALL cells were intravenously injected with an anti-IL7α antibody (clone 40131, R&D Systems) or isotype control antibody at multiple time intervals and sacrificed after showing signs of leukemia or when they had at least 75% blasts in peripheral blood (page 28, ¶ 00129). Separately, the methods section also recites that NSG mice injected with BCR-ABL-positive ABL were treated in vivo with ruxolitinib, imatinib, and antibody, but specific details regarding the “antibody” are not disclosed (page 29, ¶ 00134).
Example 8 (pages 35-36) discloses that Applicant tested whether direct targeting of IL7R using specific monoclonal antibodies interferes with its function in leukemia by injecting imatinib-resistant BCR-ABL1+ ALL patient cells into NSG mice and treating the mice with a monoclonal antibody specific for IL7Rα (Figure 7A-7C), citing Alsadeq (Letters to Blood (2018) 132(15): 1614-1617) for support. Alsadeq discloses that the antibody used in the method was clone 40131 from R&D Systems (caption, Figure 2), which corresponds to R&D Systems Cat. No. MAB306. R&D Systems discloses that MAB306 binds to the extracellular domain of human IL-7Rα. See R&D Systems’ product data sheet in Office Action Appendix. The experiment was repeated using xenografts from imatinib-resistant BCR-ABL1 harboring a T315I mutation, and anti-IL-7R antibody treatment significantly delayed leukemia onset and prolonged survival (Figures 7D-7F, 18C). Applicant discloses that the antibody used in the treatment method does not block IL-7 binding (Figure 20A).
The disclosure also separately describes anti-IL7R antibodies comprising a heavy chain or heavy chain variable region (VH) having the amino acid sequence of one of SEQ ID NO: 1, 5, or 7, and a corresponding light chain or light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 8 (e.g., page 23; Figure 23). However, the examples do not describe how said antibodies were generated. The Drawings do not show any data illustrating the specific affinity of said antibodies for IL-7R or what epitope(s) of IL-7R is bound by said antibodies. Further, neither the disclosure nor the drawings indicate whether said antibodies do not prevent IL-7 from binding to IL-7R, or illustrate the use of said antibodies in a method of treating Ph+ ALL.
MPEP § 2163 states that 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. While the claims are broadly drawn to compositions comprising an anti-IL-7R antibody that does not prevent binding of IL-7 to IL-7R, and use thereof in a method of treating Ph+ ALL, the disclosure only clearly describes one such antibody (clone 40131, R&D Systems) and said antibody is commercially available. The properties of the remaining anti-IL-7R antibodies described elsewhere in the disclosure, comprising a heavy chain or VH having the amino acid sequence of SEQ ID NO: 1, 5, or 7, and a light chain or VL having the amino acid sequence of SEQ ID NO: 8, are not sufficiently well described such that one of ordinary skill in the art would recognize that these antibodies bind to IL-7R, do not prevent binding of IL-7 to IL-7, or bind or do not bind to a ligand-binding site of IL-7R. Furthermore, because the specific epitope of these antibodies is not clearly described, one of ordinary skill in the art would be unable to identify other antibodies that compete for binding with said antibody.
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. While the disclosure describes a complete structure (heavy chain or VH and light chain or VL) of a small number of antibodies, having very structurally similar CDR structures, the binding properties or other functional attributes of these antibodies do not appear to be characterized in the disclosure.
Conclusion. For all of the reasons presented above, one of skill in the art would not know which of the countless other antibodies encompassed by the highly general structural requirements of the claims would also possess the required functional activity. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess the full genus of antibodies as broadly claimed at the time the application was filed.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claims 4-11 and 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jumaa-Weinacht (WO 2020/077190 A1; published April 16, 2020; earliest priority date: October 12, 2018; supra).
The applied reference has common inventors (Jumaa-Weinacht and Jumaa) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Jumaa-Weinacht discloses compositions and methods of use thereof for the treatment of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL), said composition comprising an anti-IL-7A antibody (e.g., Abstract). Regarding claims 4-7, Jumaa-Weinacht discloses a heavy chain sequence (¶ 0095) having 100% sequence identity to instant SEQ ID NO: 1 and a light chain sequence (¶ 0096) having 100% sequence identity to instant SEQ ID NO: 8, with their respective CDRs. Regarding claims 8-9, Jumaa-Weinacht discloses that the underlined T at position 053 of the heavy chain can be substituted with A, thereby producing a heavy chain matching the amino acid sequence of instant SEQ ID NO: 5. Regarding claims 10-11, Jumaa-Weinacht discloses that the H at position 058 can be N, thereby producing a heavy chain matching the amino acid sequence of instant SEQ ID NO: 7.
Regarding claim 18, Jumaa-Weinacht discloses a method for treatment of ALL that comprises administering a therapeutically effective amount of an anti-IL-7R antibody to a patient in need thereof (e.g., pages 20-22; claims 1-4, 21).
Claims 1-2, 13-16, 18, and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Poirier (EP 3,423,496 B1; published July 3, 2019) and as evidenced by De (US 2018/0252708 A1).
Poirier discloses humanized antibodies that bind to the extracellular domain of the alpha chain of IL-7R which do not interfere with the IL-7 or TSLP signaling pathways and do not have an agonistic effect on the IL-7R (e.g., Abstract; ¶ 0037), relevant to claims 1-2. Regarding claims 13-16, Poirier discloses methods of making an anti-IL-7R antibody of the invention, using host cells, vectors, and nucleic acid sequences encoding said antibody (e.g., ¶ 0038-0045, 0062-0069).
Regarding claim 18, Poirier discloses using an anti-IL-7R antibody of the invention in methods of treating acute lymphoblastic leukemia (e.g., ¶ 0056).
Regarding claim 35, De provides evidence that IL7R is among several receptors or signaling markers that can be applied for prognostic or diagnostic evaluation and drug discovery in Ph+ ALL (¶ 0037). Based on the teachings of De, one of ordinary skill in the art would reasonably expect that IL-7R is implicated in Ph+ ALL and that an antibody that specifically binds to IL-7R could be used in a method of treating Ph+ ALL.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Poirier (EP 3,423,496 B1; supra) in view of De (US 2018/0252708 A1; supra).
The teachings of Poirier are recited in the 35 U.S.C. § 102 rejection above.
However, Poirier does not expressly teach a method of treating a patient with Ph+ ALL by administering an anti-IL-7R antibody that does not complete for binding with IL-7.
The teachings of De are recited in the 35 U.S.C. § 102 rejection above.
Based on the suggestion of De, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out a method of treating a patient with Ph+ ALL by administering an anti-IL-7R antibody, such as that disclosed by Poirier, that does not compete for binding with IL-7. The skilled artisan would have been motivated to do so because De teaches that IL-7R has prognostic value in Ph+ ALL, and furthermore, Ph+ ALL patients have a clear need to be treated for their illness. There would have been a reasonable expectation of success because the antibody disclosed by Poirier has utility in treating other forms of acute lymphoblastic leukemia.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 18, 35, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, 21-24, 26-30, and 32-36 of co-pending Application No. 17/222,761 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instantly claimed invention.
Co-pending claims 19, 21, 29-30, 32, and 36 recite a method for treating Ph+ ALL that is resistant to treatment with an ABL kinase inhibitor, comprising administering a monoclonal antibody configured to bind in a ligand-independent manner to IL7R. Co-pending claims 22-24, 26-28, and 33-35 further recite a method for treating Ph+ ALL that comprises administering a monoclonal antibody configured to bind in a ligand-independent manner to IL7R in combination with a tyrosine kinase inhibitor. Said treatment methods necessarily require possession of a (pharmaceutical) composition for use in treating Ph+ ALL.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 13-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, 21-24, 26-30, and 32-36 of co-pending Application No. 17/222,761 (reference application) as applied to claims 1-2, 18, 35, and 38 above, further in view of Poirier (EP 3,423,496 B1; supra).
The teachings of the reference patent are recited in the non-statutory double patenting rejection above.
However, the reference does not disclose a method of making an antibody that specifically binds to IL-7R, wherein the antibody does not prevent binding of IL-7R to IL-7.
The teachings of Poirier are recited in the 35 U.S.C. § 102 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out a method of making an anti-IL-7R antibody that does not prevent binding of IL-7 to IL-7R for use in treating Ph+ ALL based on the teachings of Poirier. The skilled artisan would have been motivated to do so because the antibodies disclosed by Poirier do not lead to strong lymphopenia due to the prevention of IL-7-dependent thymic T cells generation (¶ 0037). There would have been a reasonable expectation of success because
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:00am - 5:30pm EST.
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, Julie Wu can be reached at (571) 272-5205. 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.
/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643