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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US21/18698 filed February 19, 2021, which claims the benefit of US Provisional Application Nos. 62/979,859 filed February 21, 2020 and 63/092,575 filed October 16, 2020. All claims have been given an effective filing date of February 21, 2020.
Claim Status
Claim listing filed on August 10, 2022 is pending. Claims 8-41, 44-45, 55-58, and 62-102 are canceled. Claims 5-6, 42-43, 46-47, 52-53, and 59 are amended. Claims 1-7, 42-43, 46-54, and 59-61 are examined upon their merits.
Information Disclosure Statement
The information disclosure statements filed on 10/26/2022 and 03/08/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure (substitute specification filed 01/19/2023) is objected to because of the following informalities:
Page 112, line 8: “exmaples” should be corrected to “examples.”
Page 212, line 23: “Exmaple” should be corrected to “Example.”
Page 221, line 2: “signfiicant” should be corrected to “significant.”
Page 226, line 9: “specfiicity” should be corrected to “specificity.”
Page 226, line 9: “tehter” should be corrected to “tether.”
Page 226, line 22: “demosntrate” should be correct to “demonstrate.”
The numbering of the tables should be chronological in order of appearance. Currently, there are multiple tables that are unlabeled and multiple tables with repeat numbers (at least four tables are labeled “Table 2”). In order of appearance, the tables should be labeled “Table 1”, “Table 2”, “Table 3”, etc.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Specifically, there are three hyperlinks on page 41. 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.
Appropriate correction is required. Applicant is urged to carefully review the specification for additional informalities.
Claim Objections
Claims 1, 42, 46-47, and 52 are objected to because of the following informalities:
Claims 1 and 42 recite “intestine target moiety” and should be corrected to “intestine targeting moiety.”
Claim 42 recites “Lc” in the last line which should be corrected to “Lc” wherein the “c” is in subscript.
Claims 46-47 recite “claims 42” and should be corrected to “claim 42.”
Claim 52 recites “does not comprises” and should be corrected to “does not comprise.”
Appropriate correction is required.
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.
Claims 1-2, 4-7, 42-43, 46-54, and 59-61 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 recites “a skin targeting moiety or an intestine targeting moiety that binds to a target cell in the skin or the intestine.” Claims 4-6 and 59-61 are dependent on Claim 1 and do not further define the claimed targeting moieties. This phrase is considered functional language because the feature (a targeting moiety) is defined by what it does (binds to a target cell in the skin or the intestine) rather than by what it is (MPEP § 7173.05(g)). To determine if functional language is ambiguous, the following factors are considered: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim. These factors are examples of points to be considered when determining whether language is ambiguous and are not intended to be all inclusive or limiting (MPEP § 7173.05(g)). Claim 1 only states a result obtained and is non-limiting in potential structure necessary to perform the stated function. Therefore, the metes and bounds of these moieties cannot be readily determined, and Claims 1, 4-6, and 59-61 are rejected as being indefinite.
Claim 5 recites “wherein the immune cell contributes to an unwanted immune response,” and Claim 6 recites “wherein the immune cell causes a disease pathology.” These phrases are considered functional language because the feature (the immune cell) is defined by what it does (contributes to an immune response and causes a disease pathology) rather than by what it is (MPEP § 7173.05(g)). The metes and bounds of these immune cells cannot be readily determined, and Claims 5-6 are rejected as being indefinite.
Claims 2 and 7 recite the limitation "the targeting moiety" in line 1. There is insufficient antecedent basis for this limitation in the claim, because two targeting moieties are defined in Claim 1 (a skin targeting moiety and an intestine targeting moiety) and it is unclear which moiety is referenced by “the targeting moiety.” For the purpose of compact prosecution, “the targeting moiety” is interpreted as “the skin targeting moiety.”
Claim 42 is unclear because it defines wherein the effector binding/modulating moiety is a PD-1 agonist or an IL-2 mutein in lines 3-4, and then defines wherein the binding/modulating moiety is required to be an IL-2 mutein in lines 11-12. For the purpose of compact prosecution, Claim 42 is interpreted wherein the effector binding/modulating moiety is a PD-1 agonist or an IL-2 mutein, and in instances when the modulating moiety is an IL-2 mutein, then the limitations of lines 11-12 apply.
Claim 46 recites wherein the IL-2 mutein further comprises a mutation at positions 69, 75, 88, or 125, and Claim 47 recites wherein a mutation is selected from the group consisting of L53I, L56I, L80I, L118I, V69A, Q74P, N88D, or N88R. These claims are unclear because the IL-2 mutein comprises SEQ ID NO: 60 (as defined in Claim 42), and SEQ ID NO: 60 comprises N88D, V69A, Q74P, C125S, and at least one I at positions 53, 56, 80, or 118 (specification page 74). It is unclear how the mutations listed in Claims 46-47 can be in addition to the IL-2 mutein comprising SEQ ID NO: 60 which already comprises the mutations. Further, Claim 46 recites a mutation at position 75, but the specification makes clear that the mutation is at position 74 (page 59, line 30). It is interpreted that position 75 was meant to recite position 74, but clarifying correction is required.
Claim 59 recites “a method of treating a subject with inflammatory bowel disease, GVHD, a skin auto-immune disorder as provided herein…to treat the inflammatory bowel disease.” It is unclear if Claim 59 is directed to a method of treating a subject with (1) inflammatory bowel disease, GVHD, or a skin auto-immune disorder; (2) inflammatory bowel disease, GVHD, and a skin auto-immune disorder; or (3) inflammatory bowel disease. For the purpose of compact prosecution, Claim 59 is interpreted with the broadest reasonable interpretation of treating all three diseases in the alternative (option (1)). Claims 59-61 are rejected for indefiniteness.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 46-47 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 46 recites wherein the IL-2 mutein further comprises a mutation at positions 69, 75, 88, or 125, and Claim 47 recites wherein a mutation is selected from the group consisting of L53I, L56I, L80I, L118I, V69A, Q74P, N88D, or N88R. However, Claims 46-47 depend from Claim 42 which defines that the IL-2 mutein comprises SEQ ID NO: 60 which comprises N88D, V69A, Q74P, C125S, and at least one I at positions 53, 56, 80, or 118 (specification page 74). Therefore Claims 46-47 either fail to further limit Claim 42 because they recite the same mutations of SEQ ID NO: 60 or fail to include all the limitations of the Claim 42 because they recite alternative mutations (N88R or C125A).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-2, 4-6, 42, 46-54, and 59-61 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is directed towards a polypeptide comprising a skin targeting moiety or an intestine targeting moiety that binds to a target cell in the skin or the intestine. Therefore, Claim 1 encompasses a genus of targeting moieties that can have any structure. Claims 2 and 42 define wherein the targeting moiety is an antibody that binds to a target cell in the skin or the intestine, resulting in a genus of targeting antibodies.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. In order to provide adequate written description and evidence of possession of the claimed genus of targeting moieties, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In the instant case, the specification teaches antibodies directed towards one intestine cell target (anti-MAdCAM, Example 6 and tables spanning pages 114-157) and one skin cell target (desmoglein 1, page 226 lines 7-24). Examples of antibodies directed to one intestine cell target and one skin cell target are not sufficient to describe the genus of targeting moieties directed to any skin or intestine target. 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) (MPEP § 2163.05.Ib). In the absence of sufficient recitation of distinguishing identifying characteristics or structure-to-function attributes for the entire genus of targeting moieties, the specification does not provide adequate written description of the claimed genus.
Note, listing protein targets without teaching the structures capable of binding said targets (as on pages 83-85) is not sufficient written description of the targeting moieties. MPEP § 2163.II.A.3 teaches that disclosure of an antigen without more does not provide adequate written description of an antibody claimed by its binding to that antigen, even when preparation of such an antibody is routine and conventional (Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)).
Therefore, in view of the case law directed to an appropriate number of representative species and proper written description of antibodies, claims 1-2, 4-6, 42, 46-54, and 59-61 are rejected for insufficient written description.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claims 1-2, 4-6, 42, 46-54, and 59-61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the targeting moieties comprising anti-MAdCAM and anti-desmoglein 1 antibodies and those known in the art prior to filing, does not reasonably provide enablement for the genus of targeting moieties that bind to target cells in the skin or intestine. 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.
MPEP § 2164.01(a) states that there are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure
does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims and nature of the invention:
The nature of the invention is complex. As understood with the broadest reasonable interpretation, Claim 1 encompasses a genus of targeting moieties that can have any structure as long as they effectively bind target cells in the skin or intestine. Claims 2 and 42 define wherein the targeting moiety is an antibody that binds to a target cell in the skin or the intestine, resulting in a genus of targeting antibodies.
When analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be "given their broadest reasonable interpretation consistent with the specification." See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
The state of the prior art and level of predictability in the art:
The level of predictability in the art depends, most importantly, on whether the claimed invention can be practiced by one of ordinary skill in the art. Stanley WO 2008/085987 teaches a composition comprising an antibody-protein fusion molecule wherein said antibody is non-pathogenic to its target tissue and said protein is a therapeutic protein (Stanley Claim 1). The antibody binds to skin protein targets desmoglein 1 (Dsg1) or desmoglein 3 (Dsg3) (Viney Claim 4) and specifically comprises the sequences listed in Fig. 17A-B. While Viney teaches two examples of antibodies that target Dsg1 and Dsg3 on the surface of skin cells, the instant claims are much broader, encompassing moieties that bind any targets in the skin or intestine.
Further, in AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions. The case law applies to the instant claims which encompass a genus of antibodies that bind cells in the skin or intestine, yet the inventors have only disclosed two species: anti-MAdCAM and anti-desmoglein 1.
In Amgen, the Supreme Court has stated that despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody's structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody's structure and function. Ibid. The unpredictability of antibody structure applies to the genus of antibodies claimed in the instant application.
The case law shows a continued lack of predictability even after the effective filing date of the instant invention, and there is no support in the Applicant’s disclosure leading one of ordinary skill to overcome the lack of predictability in the genus of targeting moieties claimed. The specification provides no guidance or direction for structure that must be maintained such that the functional properties of the invention are preserved (binding target cells in the skin or intestine).
Level of skill in the art:
The level of skill would be high encompassing protein science, antibodies, binding assays, molecular biology, etc.
Amount of direction provided by inventor and the existence of working examples:
The specification teaches antibodies directed towards one intestine cell target (anti-MAdCAM, Example 6 and tables spanning pages 114-157) and one skin cell target (desmoglein 1, page 226 lines 7-24).
However, two species do not adequately represent the scope of targeting moieties that bind to any target cell in the skin or intestine. A person having ordinary skill in the art would have to make a substantial inventive contribution in order to make and characterize a representative number of targeting moieties that bind to a representative number of skin and intestine targets to encompass the claimed genus.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In light of the unpredictability surrounding the claimed subject matter, the undue breadth of the claimed invention’s intended use, and the lack of adequate guidance, one wishing to make and practice the presently claimed invention would be unable to do so without engaging in undue experimentation. Given that structure is essential to function, a person having ordinary skill in the art would have to perform further experimentation to make the targeting moieties encompassed by the claims and screen their characteristics in order to practice the invention commensurate with the scope of the claims.
The instant specification does not enable the invention to make and use the entire genus of targeting moieties that bind to target cells in the skin or intestine; therefore, Claims 1-2, 4-6, 42, 46-54, and 59-61 are rejected.
Note, “treating” in Claim 59 is defined by the specification to include both therapeutic treatment (ameliorating symptoms) and prophylactic treatment (preventing or reducing the disease before the onset) (pages 20-21). Therapeutic and prophylactic treatment are enabled by Example 37 in the specification and the state of the art prior to filing wherein prophylactically administering immunosuppressants before a potential autoimmune flare would have been understood by one of ordinary skill.
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.
Claims 1, 4-6, 42, 46-54, and 59-61 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Viney US 2018/0340014.
In regard to Claims 1 and 4-6, Viney teaches a polypeptide comprising a targeting moiety that binds to a target cell and an effector binding/modulating moiety wherein the effector binding/modulating moiety is an IL-2 mutein (Claim 1). The targeting moiety comprises an anti-MAdCAM antibody (Claim 7) wherein MAdCAM is present on cells in the intestine (Table 3). The IL-2 mutein can comprise SEQ ID NOs: 38, 39, 40, or 41 (page 26) which are 100% identical to instant SEQ ID NO: 60 wherein at least one of X1, X2, X3, and X4 is I and the remainder are L. Alternatively, the effector binding/modulating moiety can be a PD-1 agonist (paragraph [0116] and Fig. 3A). Instant Claims 4-6 recite inherent properties of the IL-2 mutein (MPEP § 2112.01.I-II).
In regard to Claim 42, Viney teaches that the polypeptide comprises a first chain and a second chain wherein the first chain comprises VH-HC-Linker-C1 wherein VH is a variable heavy domain that binds to the target cell with a VL domain of the second chain; HC is a heavy chain of antibody comprising CH1-CH2-CH3 domain, the Linker is a glycine/serine linker, and C1 is a IL-2 mutein fused to a Fc protein in either the N-terminal or C-terminal orientation; and the second chain comprises: VL-LC, wherein VL is a variable light chain domain that binds to the target cell with the VH domain of the first chain, and the LC domain is a light chain CK domain (Viney Claim 42). Note, positions 53, 56, 80, and 118 of SEQ ID NO: 60 correspond to X1, X2, X3, and X4 respectively.
In regard to Claims 46-52, Viney teaches that the IL-2 mutein can comprise SEQ ID NOs: 38, 39, 40, or 41 (page 26) which all comprise mutations N88D, V69A, Q74P, C125S. SEQ ID NOs: 38, 39, 40, and 41 further comprise single mutations L53I, L56I, L80I, and L118I respectively (page 26).
In regard to Claim 53, Viney teaches that the Fc region comprises a L234A mutation, a L235A mutation, and/or a G237A mutation (paragraph [0238]). Alternatively, the Fc region comprises mutations L247A, L238A, and G250A (paragraph [0238]).
In regard to Claim 54, Viney teaches non-limiting examples of glycine/serine linkers comprising SEQ ID NOs: 22 and 30 which are 100% identical to instant SEQ ID NOs: 22 and 30 respectively.
In regard to Claims 59-61, Viney teaches a method of treating inflammatory bowel disease or GVHD by administering the polypeptide (Viney Claims 56 and 59). Treatment of inflammatory bowel disease encompasses Crohn’s disease and ulcerative colitis (paragraphs [0046] and [0277]).
Therefore, Claims 1, 4-6, 42, 46-54, and 59-61 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Viney.
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.
Claims 2-3, 7, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Viney US 2018/0340014 as applied to Claims 1, 4-6, 42, 46-54, and 59-61 above, and further in view of Stanley WO 2008/085987.
The teachings of Viney as they apply to Claims 1, 4-6, 42, 46-54, and 59-61 are outlined in the rejection above. Viney further teaches that the targeting moiety could bind desmoglein 1-4 to target skin cells to treat the skin auto-immune disorder vitiligo (paragraph [0277] and Table 3). Example 8 (paragraph [0477]) teaches a polypeptide wherein the anti-MAdCAM antibody was exchanged for a different targeting moiety (anti-H-2Kk), and the results demonstrated that tethering is not specific to MAdCAM and other molecules can act as targeting moieties.
Viney fails to teach wherein the targeting moiety is an antibody that binds a target protein on the surface of a skin cell, specifically an antibody that binds desmoglein 1-4 (Claims 2-3, 7, and 43).
Stanley teaches a composition comprising an antibody-protein fusion molecule wherein said antibody is non-pathogenic to its target tissue and said protein is a therapeutic protein (Stanley Claim 1). The antibody binds to desmoglein 1 (Dsg1) or desmoglein 3 (Dsg3) (Viney Claim 4). The composition is administered as a method of treatment for targeted delivery of the therapeutic protein to a site of interest, specifically the epidermis (Viney Claims 20-21). Viney teaches the sequences of scFv antibodies that target Dsg1 or Dsg3 (Fig. 17A-B).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to substitute the anti-MAdCAM antibody targeting moiety taught by Viney for the anti-Dsg1 or anti-Dsg3 antibodies taught by Stanley. Viney teaches that the targeting moiety can be exchanged with other known moieties that bind targets of interest, and desmoglein 1-4 are targets of interest to direct therapy to the skin. Stanley teaches anti-Dsg1 and anti-Dsg3 antibodies that are also used for targeted therapy to direct therapeutic proteins to the skin. One of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. The motivation to make the targeting moiety an anti-Dsg1 or anti-Dsg3 antibody is to provide targeted delivery to the skin to treat auto-immune diseases such as vitiligo (Viney paragraph [0277] and Table 3).
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.
1. Claims 1, 42, and 46-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-13 of U.S. Patent. No. 10,676,516. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims recite a polypeptide comprising a targeting moiety that binds to a target cell in the skin or intestine and an effector binding/modulating moiety comprising an IL-2 mutein comprising SEQ ID NO: 60 wherein at least one of X1, X2, X3, and X4 is I and the remainder are L or I (Claim 1). Claim 42 recites the same polypeptide as Claim 1 wherein the targeting moiety is an antibody and comprises two chains: (1) VH-HC-Linker-C1 wherein VH is a variable heavy domain that binds to the target cell with a VL domain of the second chain; HC is a heavy chain of antibody comprising CH1-CH2-CH3 domain, the Linker is a glycine/serine linker, and C1 is a IL-2 mutein fused to a Fc protein in either the N-terminal or C-terminal orientation and (2) VL-LC, wherein VL is a variable light chain domain that binds to the target cell with the VH domain of the first chain, and the LC domain is a light chain CK domain. SEQ ID NO: 60 comprises the mutations N88D, V69A, Q74P, C125S, and one of L53I, L56I, L80I, or L118I (Claims 46-52). The Fc protein comprises L247A, L238A, G250A, or a L234A mutation, a L235A mutation, and/or a G237A mutation (Claim 53).
The patented claims recite a polypeptide comprising an anti-MAdCAM antibody and an IL-2 mutein that comprises SEQ ID NO: 6 and mutations N88D, V69A, Q74P, C125S, and one of L53I, L56I, L80I, or L118I (Claims 1-3, 5, 10-13). Note, an anti-MAdCAM antibody targets intestine cells, and patented SEQ ID NO: 6 with the claimed mutations is 100% identical to instant SEQ ID NO: 60. The patented claims further recite wherein the polypeptide comprises two chains: (1) VH-HC-Linker-C1 the Linker is a glycine/serine linker, and C1 is a IL-2 mutein fused to a Fc protein in either the N-terminal or C-terminal orientation and (2) VL-LC (Claim 9). The Fc protein comprises mutations at L247, L238, and G250, or a L234A mutation, a L235A mutation, and/or a G237A mutation (Claims 6-8).
Because the patented claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the patented claims.
2. Claims 1 and 42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent. No. 10,961,310. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant Claims 1 and 42 are recited above. Claims 1 and 42 further recite wherein the effector binding/modulating moiety can be an IL-2 mutein or a PD-1 agonist.
The patented claims recite a therapeutic compound comprising Chain 1: [VH1-CH1]-[CH2-CH3]-Linker A – scFv and Chain 3: [VL1-CL] wherein the VH1-CH1 domain comprises a Fab that is an anti-PD-1 agonist antibody and the scFv binds to MAdCAM (Claim 1). Claim 5 recites wherein the peptide linker is a glycine/serine linker.
Because the patented claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the patented claims.
3. Claims 1, 42, and 46-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7, and 11 of U.S. Patent. No. 11,466,068. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant Claims 1, 42, and 46-53 are recited above.
The patented claims recite a method of increasing Treg cell proliferation by administering a polypeptide comprising an anti-MAdCAM antibody and an IL-2 mutein that comprises SEQ ID NO: 6 and mutations N88D, V69A, Q74P, C125S, and one of L53I, L56I, L80I, or L118I (Claims 1 and 7). Note, patented SEQ ID NO: 6 with the claimed mutations is 100% identical to instant SEQ ID NO: 60. The patented claims further recite wherein the polypeptide comprises two chains: (1) VH-HC-Linker-C1 the Linker is a glycine/serine linker, and C1 is a IL-2 mutein fused to a Fc protein in either the N-terminal or C-terminal orientation and (2) VL-LC (Claim 4). The Fc protein comprises mutations at L247, L238, and G250, or a L234A mutation, a L235A mutation, and/or a G237A mutation (Claims 2-3 and 11).
Because the patented claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the patented claims.
4. Claims 1-3 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent. No. 11,981,715. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant Claim 1 is recited above. Claims 2-3 and 7 are directed to the targeting moiety comprising an anti-desmoglein 1-4 antibody.
The patented claims recite a polypeptide comprising a skin targeting moiety that binds to a target cell and an effector binding/modulating moiety wherein the skin targeting moiety comprises an anti-desmoglein 1 antibody and the effector binding/modulating domain is a PD-1 agonist or an IL-2 mutein comprising SEQ ID NO: 60 wherein at least one of X1, X2, X3, and X4 is I and the remainder are L or I (Claim 1). Note, patented SEQ ID NO: 60 is 100% identical to instant SEQ ID NO: 60.
Because the patented claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the patented claims.
5. Claims 1, 42, and 59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, 23, 36, and 38 of copending U.S. App. No. 18/547,183.
Instant claims 1 and 42 are recited above. Claim 59 recites a method of treating inflammatory bowel disease or GVHD by administering the polypeptide of claim 1.
The copending claims recite: an anti-PD-1 agonist (Claim 1); wherein the anti-PD-1 agonist is linked with a targeting moiety that is optionally an anti-MAdCAM antibody (Claims 21 and 23); a method of treating inflammatory bowel disease by administering the antibody of claim 1 (Claim 36); and a method of treating GVHD by administering the antibody of claim 1 (Claim 38).
Because the copending claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
6. Claims 1, 42, and 59-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of copending U.S. App. No. 18/819,116.
Instant claims 1, 42, and 59 are recited above. Claims 60-61 recite wherein the inflammatory bowel disease includes Crohn’s disease and ulcerative colitis.
The copending claims recite: a compound comprising an anti-PD-1 antibody and an anti-MAdCAM antibody wherein a first chain comprises (1) VH-HC-Linker-C1 and a second chain comprises (2) VL-LC (Claims 1 and 3); the peptide linker is a glycine/serine linker (Claim 2); and a method of treating inflammatory bowel disease, Crohn’s disease, ulcerative colitis, or GVHD by administering the compound of claim 1 (Claim 8). Note, the copending specification defines that the anti-PD-1 antibody is an agonist (paragraph [0081]).
Because the copending claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7. Claims 1-3, 7, 42-43, and 46-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 38, 55, 58-59, 60, and 74 of copending U.S. App. No. 18/248,401.
Instant claims 1-3, 7, 42, and 46-53 are recited above. Claim 43 recites wherein the VL and VH domains are anti-desmoglein 1, 2, 3, or 4 variable domains. Claim 54 recites wherein the linker comprises SEQ ID NOs: 30 or 22.
The copending claims recite: a protein comprising a skin targeting moiety comprising an anti-desmoglein 1, 2, 3, or 4 antibody and an effector binding/modulating moiety comprising a PD-1 agonist or IL-2 mutein (Claim 1); the IL-2 mutein comprises SEQ ID NO: 60 and at least one of L53I, L56I, L80I, or L118I and the remainder are L or I (Claim 38); the IL-2 mutein is linked to a Fc protein comprising mutations at L247, L238, and G250, or a L234A mutation, a L235A mutation, and/or a G237A mutation (Claims 55 and 58-59); the polypeptide comprises two chains: (1) VH-HC-Linker-C1 wherein the Linker is a glycine/serine linker, and C1 is a IL-2 mutein fused to a Fc protein in either the N-terminal or C-terminal orientation and (2) VL-LC (Claim 60); and the linker comprises SEQ ID NOs: 30 or 22 (Claim 74). Note, copending SEQ ID NOs: 60, 30, and 22 are 100% identical to instant SEQ ID NO: 60, 30, and 22 respectively.
Because the copending claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8. Claims 1, 42, and 59-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 16-18, 24-26, and 31 of copending U.S. App. No. 18/252,081.
Instant claims 1, 42, and 59-61 are recited above. Note, “treating” in Claim 59 is defined by the specification to include both therapeutic treatment (ameliorating symptoms) and prophylactic treatment (preventing or reducing the disease before the onset) (pages 20-21).
The copending claims recite: an anti-MAdCAM antibody that is linked with an effector molecule comprising a PD-1 agonist (Claims 7 and 16-18); and a method of treating or preventing inflammatory bowel disease, Crohn’s disease, ulcerative colitis, or GVHD by administering the antibody of Claim 7 (Claims 24-26 and 31).
Because the copending claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
9. Claims 1 and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending U.S. App. No. 18/264,940.
Instant claims 1 and 42 are recited above.
The copending claim recites a method of treating Type 1 diabetes comprising administering an anti-PD-1 agonist antibody linked to an anti-MAdCAM antibody (Claim 1).
Because the copending claims recite the same elements of the instant claims, the instant claims are either anticipated and/or rendered obvious by the copending claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm 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, Jeffrey Stucker can be reached at (571) 272-0911. 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.
/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/STACEY N MACFARLANE/Examiner, Art Unit 1675