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 .
Claim Status
Claims 2, 6, 8-9, 15-40, and 45 have been cancelled; claims 1, 42, and 46 have been amended; and, claims 47-50 have been newly added, as requested in the amendment filed on 12/29/202. Following the amendment, claims 1, 3-5, 7, 10-14, 41-44, and 46-50 are pending in the instant application.
Claims 1, 3-5, 7, 10-14, 41-44, and 46-50 are under examination in the instant office action.
Priority - Updated
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.
Claims 1, 3-5, 7, 10-14, 41-44, and 46-50 have an effective filing date of May 10, 2019 corresponding to PRO 62/846,494.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/29/2025 and 01/08/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification - Objections Withdrawn
The specification was objected to for failing to properly identify and/or represent trade names and marks used in commerce. Applicant has amended the specification such that all trade names and marks used in commerce are now properly represented and are accompanied by their generic terminology. As such the objection to the specification is withdrawn.
The abstract of the disclosure was objected to because the abstract was fewer than 50 words in length. Applicant has submitted an amended abstract that is between 50 and 150 words in length. As such, the objection to the abstract of the disclosure is withdrawn.
Claim Rejections - 35 USC § 112 - Withdrawn
Claims 1, 3-5, 7, 10-16, and 41-44 were rejected under 35 USC § 112(a) for failing to comply with the written description requirement. Applicant has amended claim to incorporate the elements of previously presented claim 45, which provides a structural representation for the amino substituted compound (D-NH-). As such, claim 1, and all subsequently dependent claims, are adequately described and comply with the written description requirement. Thus, the rejection of claims 1, 3-5, 7, 10-16, and 41-44 under 35 USC § 112(a) for failing to comply with the written description requirement is withdrawn.
Claim 42 was rejected under 35 USC § 112(a) regarding scope of enablement. Applicant has amended claim 42 such that the claim now recites “[a] method of therapeutically treating cancer in a subject”; this amendment to recite “therapeutically treating cancer” limits the treatment method to patients having cancer, and as such claim 42 is no longer drawn to preventative/prophylactic treatment methods. As such, claim 42 is considered to be enabled. Thus, the rejection of claim 42 35 USC § 112(a) regarding scope of enablement is withdrawn.
Claim Objections - New - Necessitated by Amendment
PNG
media_image1.png
128
474
media_image1.png
Greyscale
Claim 50 is objected to because of the following informalities: one of the structures, reproduced below, is not clearly/properly represented. It is noted that it appears two -NH groups of the structure are overlapping and therefore appear to be represented in the structure just as -N which may or may not be bonded (circled in the structure below). Appropriate correction is required.
Claim Rejections - 35 USC § 103 - Withdrawn
Claims 15-16 and 45 were rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/200821 A1 (previously cited on PTO-892; herein after referred to as "Bruml") in view of WO 2019/092660 A1 (previously cited on PTO-892; herein after referred to as "Vyskocil"), non-patent literature by Gallery et. al. (PLOS ONE, 2018, 13(1), 1-20; previously cited on PTO-892; herein after referred to as "Gallery"), WO 01/27074 A1 (herein after referred to as "Raje"), WO 2008/092168 A2 (previously cited on PTO-892; herein after referred to as "Mizori"), and non-patent literature by Pasut and Veronese (Journal of Controlled Release, 2012, 161, 461-472; previously cited on PTO-892; herein after referred to as "Pasut") as evidenced by Gonzalez and Vaillard (Current Organic Chemistry, 2013, 17(9); herein after referred to as “Gonzalez”). It is noted that claims 15-16 and 45 have been cancelled, rendering their rejection moot. As such, the rejection of claims 15-16 and 45 under 35 U.S.C. 103 over Bruml, Vyskocil, Gallery, Raje, Mizori, Pasut, and Gonzalez is withdrawn.
Claim Rejections - 35 USC § 103 - Updated as Necessitated by Amendment
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-5, 7, 10-14, 41-44, and 46 stand as rejected, and new claims 47-50 are newly rejected, under 35 U.S.C. 103 as being unpatentable over WO 2018/200821 A1 (previously cited on PTO-892; herein after referred to as "Bruml") in view of WO 2019/092660 A1 (previously cited on PTO-892; herein after referred to as "Vyskocil"), non-patent literature by Gallery et. al. (PLOS ONE, 2018, 13(1), 1-20; previously cited on PTO-892; herein after referred to as "Gallery"), WO 01/27074 A1 (herein after referred to as "Raje"), WO 2008/092168 A2 (previously cited on PTO-892; herein after referred to as "Mizori"), and non-patent literature by Pasut and Veronese (Journal of Controlled Release, 2012, 161, 461-472; previously cited on PTO-892; herein after referred to as "Pasut") as evidenced by Gonzalez and Vaillard (Current Organic Chemistry, 2013, 17(9); herein after referred to as “Gonzalez”).
With regard to new claims 47-50, Bruml teaches immunoconjugates comprising antibodies conjugated with STING agonists, pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and combinations thereof, which are useful for the treatment of diseases, in particular, cancer (Page 1, Lines 28-30). The immunoconjugates of the invention comprise an antibody (Ab), or functional fragment thereof, couped to a STING receptor agonist (D) via a linker (L), wherein the linker optionally comprises one or more cleavage elements, as represented by Formula (I): Ab-(L-(D)m)n wherein m is an integer from 1 to 8 and n is an integer from 1 to 20 (Pages 2-3). Bruml further teaches various linker components (pages 209-216). Bruml further discloses exemplary self-immolative spacers, including the formula shown below (Page 211).
PNG
media_image2.png
272
402
media_image2.png
Greyscale
PNG
media_image3.png
121
141
media_image3.png
Greyscale
It is specifically noted that PG is a protecting group, Xc can be an NH group, Yb can be a bond or a CH2 group, and LG is a leaving group such as a drug moiety (D) of immunoconjugates of the invention. (Id.). As such, Bruml reads on the portion of instant Formula I shown below, wherein n=0 or 1, m=0, and R3, R3’ and R2 are hydrogen.
However, it is noted that according to the instant invention, R2 cannot be hydrogen but rather must be a C1-4 alkyl or –(CH2CH2O)s-CH3 wherein s is an integer from 1-10. Thus, while Bruml suggests most of the components of instant Formula (I), but does not teach or suggest R2 as defined by the present invention. However, it is well established in the art that substitution of a hydrogen for a methyl group is obvious absent unexpected results. It is generally noted that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. In re Lincoln, 126 U.S.P.Q. 477, 53 U.S. P.Q. 40 (C.C.P.A. 1942); In re Druey, 319 F.2d 237, 138 U.S.P.Q. 39 (C.C. P.A. 1963); In re Lohr, 317 F.2d 388, 137 U.S.P.Q. 548 (C.C.P.A. 1963); In re Hoehsema, 399 F.2d 269, 158 U.S.P.Q. 598 (C.C.P.A. 1968); In re Wood, 582 F.2d 638, 199 U.S. P.Q. 137 (C.C.P.A. 1978); In re Hoke, 560 F.2d 436, 195 U.S.P.Q. 148 (C.C.PA.A. 1977); Ex parte Fauque, 121 U.S.P.Q. 425 (P.O.B.A. 1954); Ex parte Henkel, 130 U.S.P.Q. 474, (P.O.B.A. 1960). Given that applicant did not provide unexpected or unobvious results of the invention, it is concluded that the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to substitute the R2 “H” group of Bruml to a “methyl” (i.e., C1 alkyl) as required by the instant claims. Furthermore, Bruml Page 2019-216 suggests that a linker of the invention may comprise one or more linker components which can include: a self-immolative spacer. One
PNG
media_image4.png
136
270
media_image4.png
Greyscale
such self-immolative spacer is shown/discussed above, and another is shown below:
It is noted that the above self-immolative group comprises a citrulline and valine (Cit-Val), however it is further noted that Bruml teaches various possible amino acid residue combinations where a combination of two or more amino acid residues can include alanine (Ala), cysteine (Cys), aspartic acid (Asp), glutamic acid (Glu), phenylalanine (Phe), glycine (Gly), histidine (His), isoleucine (lie), lysine (Lys), leucine (Leu),methionine (Met), asparagine (Asn), praline (Pro), glutamine (Gin), arginine (Arg), serine (Ser), threonine (Thr), valine (Val), tryptophan (Trp), tyrosine (Tyr), citrulline (Cit), norvaline (Nva), norleucune (Nle), selenocysteine (Sec), pyrrolysine (Pyl), homoserine, homocysteine, and desmethyl pyrrolysine, and can more specifically include, for example, Ala-Val (Pages 209-210). Furthermore, it would have been obvious based on the structures of the two above-presented self-immolative groups that said groups could be modified such that they can be linked in the manner instantly claimed, as shown below, through the -N of the first structure and the –(CO)-O portion of the second structure (a connection that the second structure itself supports) and can include Ala-Val instead of Cit-Val to arrive at the instantly claimed linker structure below:
PNG
media_image5.png
180
360
media_image5.png
Greyscale
Bruml, as referenced above, also suggests that more than two amino acids can be included in a linker, and suggests that one amino acid capable of being included in a Lys residue, which reads on the below portion of the instantly claimed structure, which includes the Ala-Val portion of the structure above:
PNG
media_image6.png
270
755
media_image6.png
Greyscale
However, it is noted that the instantly claimed Lys residue is functionalized at both amino groups. Such a modification is not taught or suggested by Bruml. It is also noted that while Bruml teaches a STING receptor agonist (D), Bruml does not teach the structure instantly claimed nor does Bruml teach the instantly elected anti-GCC antibody.
The instantly claimed STING agonist is taught by Vyskocil, an anti-GCC antibody is taught by Gallery, and the functionalization of the Lys residue is suggested by the combination of Raje, Mizori, Pasut, and Gonzalez.
PNG
media_image7.png
740
728
media_image7.png
Greyscale
Vyskocil teaches a novel compound of Formula (I), shown below, having a STING agonistic activity, which can be useful as an agent for the treatment of cancer and other diseases (Paragraphs 0004-0005).
More specifically, Vyskocil teaches an exemplary structure for a compound of Formula (I) having the structure shown below (designated by Vyskocil as Formulas I-5a, I-5b, I-5c, and I-5d; see Page 32).
PNG
media_image8.png
222
310
media_image8.png
Greyscale
Thus, Vyskocil teaches the D-NH- component (the above structure is the corresponding D-NH2 formula) of the instant invention.
With regard to an anti-GCC antibody, Gallery teaches that Guanylyl cyclase C (GCC) is a cell-surface protein that is expressed by normal intestinal epithelial cells, more than 95% of metastatic colorectal cancers (mCRC), and the majority of gastric and pancreatic cancers; due to strict apical localization, systemically delivered GCC-targeting agents should not reach GCC in normal intestinal tissue, while accessing antigen in tumor (Abstract). The authors generated an investigational antibody-drug conjugate (TAK-264, formerly MLN0264) comprising a fully human anti-GCC monoclonal antibody conjugated to monomethyl auristatin E via a protease-cleavable peptide linker (Id.). TAK-264 was cytotoxic in vitro and in vivo to GCC-expressing cells, providing a solid scientific rationale for further preclinical and clinical development of this drug; as GCC is a highly specific colon epithelial antigen that is expressed on both primary and metastatic CRC tumors as well as gastric, esophageal, and pancreatic tumors, TAK-264 may provide a novel targeted approach for the treatment of these GCC-expressing malignancies, which are diseases of unmet medical need (Page 16, Paragraph 2).
With regard to Lys functionalization, Raje teaches novel processes for preparing differentially protected lysine derivatives via a novel p-anisaldehyde Schiff base intermediate (Abstract); use of a p-anisaldehyde Schiff base allows for the protection of the Nα and Nε amino groups of lysine, or a derivative thereof, with a different protecting group at each nitrogen atom wherein a process which proceeds via a p-anisaldehyde Schiff base intermediate demonstrates improved selectivity for the desired amino group with a minimum formation of impurities (Page 2). Thus, Raje teaches that the amino groups of Lys can independently be protected to prevent off-target reactivity during synthetic reactions.
PNG
media_image9.png
174
530
media_image9.png
Greyscale
Mizori teaches methods for preparing maleimides, polyimides and maleimide-terminated polyimides. Specifically disclosed are methods for preparing maleimides from N-substituted maleamic acids in the presence of an alcohol catalyst and an acid co-catalyst in a solvent (Abstract). In general, preparation of a maleimide starts with an initial reaction of an amine with maleic anhydride to form a maleamic acid; ring-closure of the maleamic acid then provides the desired maleimide (Paragraph 0003), but few methods have been reported to accomplish the ring-closure step and none has proven wholly satisfactory (Paragraph 0004). Mizori teaches scheme 1 for ring-closing and the formation of maleimide, presented below:
Thus, Mizori teaches a process for adding a maleimide group at an amino group.
Pasut teaches PEGylation has become an established and highly refined technology by moving forward from initial simple random coupling approaches based on conjugation at the level of lysine ε-amino group; amino PEGylation is still yielding important conjugates, currently in clinical practice, where the degree of homogeneity was improved by optimizing the reaction conditions and implementing the purification processes (Abstract). The epsilon amino group of lysine is the most exploited in PEGylation by using activated PEG carboxylates or carbonates (Page 464, Column 1, Paragraph 2), but Pasut teaches various approaches to site-specific PEGylation, including at Lys residues (see entire document). Thus, Pasut teaches PEGylation at various sites, including the ε-amino group of lysine. With regard to PEGylation, it is further noted that Bruml teaches including PEG groups (PEG2-20; see page 209); it is further noted that various PEG derivatives (including mPEG, which is instantly claimed) were well known and well established in the art as evidenced by Gonzalez (see Abstract).
Thus, the combination of elements above would suggest the structure below:
PNG
media_image10.png
316
976
media_image10.png
Greyscale
This structure corresponds to Formula (I) of claim 1 wherein: a=1, b=1, m=0, n=0, R1 is absent (m=0), R2 is C1 alkyl, R3 and R3’ are both H, L is a cleavable linker (i.e., comprises two self-immolative groups, a cleavable Ala-Val peptide, and mPEG8/maleimide functionalized Lys), Ab is an anti-GCC antibody, and D-NH is an amino-substituted compound (i.e., a STING agonist) wherein Ring A10 is a 5-membered monocyclic heteroaryl ring containing 2 heteroatoms that are N, Ring B10 is a 9-membered bicyclic heteroaryl ring comprising 4 heteroatoms that are N further substituted with O (i.e., C=O), X10 and X20 are each SH, R30, R40, and R50 are each hydrogen, on of R10 and R20 is hydrogen and the other is OH, and Ya and Yb are each O. Thus, the structure rendered obvious reads on new claims 47-50. Notably, a=1, b=1, m=0, W is the structure shown below, Z is cathepsin cleavable (i.e., the Val-Ala dipeptide is recognized by cathepsin), and a compound shown below wherein said compound is the D-NH-Linker
PNG
media_image11.png
96
141
media_image11.png
Greyscale
compound that may be conjugated to an antibody via the maleimide group.
PNG
media_image12.png
199
449
media_image12.png
Greyscale
Bruml, Vyskocil, Galley, Raje, Mizori, Pasut, and Gonzalez are all considered to be analogous to the present invention as they are in the same field of antibody-drug conjugates, STING agonists, and/or chemical functionalization. Thus, it would have been obvious to one of ordinary skill in the art to combine prior art elements according to known methods which would be expected to yield predictable results. Bruml teaches STING-agonist ADCs wherein the linker of said ADCs are comprised of one or more linker components including self-immolative groups, amino acids (one, two, or more), and PEG groups (see, for example, pages 1-3 and 209-216). Vyskocil teaches a specific STING agonist (see, for example, page 32; identical to the one instantly claimed). Gallery teaches anti-GCC antibodies in ADCs for the treatment of GCC-expressing cancer (see entire document). The combination of Raje, Mizori, Pasut, and Gonzalez suggest (i) site selective lysine modifications (Raje and Pasut) and (ii) amino-group functionalization by adding maleimide (Mizori) or PEG/mPEG groups (Pasut, evidenced by Gonzalez; Bruml also discloses the use of PEG groups in linker structures). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Thus, modifying the ADC of Bruml to comprise a combination of linker components, a specific STING agonist, and an anti-GCC antibody would be expected to yield an ADC capable of being used for the same purpose.
With regard to the claim rejections above under 35 USC § 103 in view of Bruml, Vyskocil, Gallery, Raje, Mizori, Pasut, and Gonzalez, Applicant argues the following on Pages 23-26 of Remarks (12/29/2025):
While an ortho-substituted phenyl ring is disclosed as one of many potential linking moieties that may be used in the linkers of Bruml, none of the working examples contain this moiety; absent impermissible hindsight, the skilled artisan would not have had a reason to select this particular moiety over those exemplified by Bruml, let alone combine it with other linking moieties needed to arrive at Applicant’s claimed linker.
Applicant’s linker yielded surprising and unexpected results; the claimed linker provides an improved rate of payload liberation in comparison to other linkers. Applicant specifically points to Table 28 and Paragraph 735 of the instant specification, which describes the payload release rates of ADC-9 (which comprises an ortho-substituted phenyl ring) and ADC-3 (which does not comprise an ortho-substituted phenyl ring) in a titrosomal assay that mimics cellular payload release conditions; no free payload release was observed for ADC-3 within 24 hours, whereas ADC-9 successfully released its payload with a t1/2 of 7 hours, demonstrating that the instantly claimed linker provides a markedly improved rate of payload liberation. A skilled artisan would have no reason to expect that the ortho-substituted phenyl moiety would provide such improved results based on the teachings of Bruml.
None of the additional references remedy the deficiency of Bruml; none of the additionally cited references teach or suggest the use of ortho-substituted phenyl rings as linking moieties nor how such a moiety would improve release profiles in the context of ADCs. As such, a skilled artisan would not have had a reason to prepare Applicant’s claimed conjugates based on the teachings of the cited references, either alone or when used in combination.
Applicant’s arguments have been fully considered, but are deemed not persuasive.
With regard to the arguments against primary reference Bruml, it is noted that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
PNG
media_image13.png
18
19
media_image13.png
Greyscale
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also > Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); < Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). As such, while the exemplary embodiments of Bruml may not comprise an ortho-substituted phenyl ring as a linker moiety, Bruml does disclose it and explicitly suggests its use in combination with other linking moieties including, but not limited to, other self-immolative linking groups and/or other cleavable linking groups (e.g., a combination of amino acid residues such as Ala-Val). It is further noted that Bruml indicates that linkers of the immunoconjugates of the invention comprise one or more cleavage elements and in certain embodiments the linkers of the immunoconjugates of the invention comprise two or more cleavage elements; in certain embodiments one of the cleavage elements (cleavage elements may be independently selected from self-immolative groups and groups susceptible to cleavage; see Page 207, Lines 27-34) is directly attached to a Drug moiety which, after the cleavage process, allows for release of a Drug moiety which does not comprise a fragment of the cleaved linker (i.e., free payload is released) (Page 220, Lines 5-9; emphasis added). Thus, Bruml suggests components of the instantly claimed ADC linkers (i.e., self-immolative groups, including an ortho-substituted phenyl ring, and other groups susceptible to cleavage) wherein the combination of such linker components results in free payload release. It is noted that the additionally cited references are relied on to further modify the suggested linker components of Bruml to arrive at the instantly claimed species designated as ADC-8. Notably, the additionally cited references are relied upon for the following teachings:
Vyskocil teaches the instantly claimed STING agonists.
Gallery teaches anti-GCC antibodies in ADCs for use in the treatment of GCC-expressing cancers.
The combination of Raje, Mizori, Pasut, and Gonzalez together teach/suggest site selective lysine modifications and amino-group functionalization including the addition of maleimide or PEG/mPEG groups.
Furthermore, with regard to the argument of impermissible hindsight, it is noted that “[a]ny judgement on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). The claim rejections based on the combination of Bruml, Vyskocil, Gallery, Raje, Mizori, Pasut, and Gonzalez relies on knowledge available to and within the level of ordinary skill in the art at the time the claimed invention was filed. With regard to one of ordinary skill in the art being motivated to combine the teachings of Bruml, Vyskocil, Gallery, Raje, Mizori, Pasut, and Gonzalez, it is noted that there is no requirement that an “express, written motivation to combine must appear in prior art references before a finding of obviousness.” See Ruiz v. A.B. Chance Co., 357 F.3d 1270, 1276, 69 USPQ2d 1686, 1690 (Fed. Cir. 2004). Bruml teaches STING-agonist ADCs wherein the linker of said ADCs are comprised of one or more linker components including self-immolative groups, amino acids (one, two, or more), and PEG groups (see, for example, pages 1-3 and 209-216). Vyskocil teaches a specific STING agonist (see, for example, page 32; identical to the one instantly claimed). Gallery teaches anti-GCC antibodies in ADCs for the treatment of GCC-expressing cancer (see entire document). The combination of Raje, Mizori, Pasut, and Gonzalez suggest (i) site selective lysine modifications (Raje and Pasut) and (ii) amino-group functionalization by adding maleimide (Mizori) or PEG/mPEG groups (Pasut, evidenced by Gonzalez; Bruml also discloses the use of PEG groups in linker structures). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Thus, modifying the ADC of Bruml to comprise a combination of linker components, a specific STING agonist, and an anti-GCC antibody would be expected to yield an ADC capable of being used for the same purpose.
Specifically with regard to the arguments of unexpected results, it is noted that evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential). See also MPEP 716.02e. The teachings of Bruml suggests the use of cleavable linker components, notably using said cleavable linker components adjacent to the payload for free payload release. Furthermore, it is noted that the arguments of unexpected results are not commensurate in scope with the instant claims. Specifically, instant claim recites a compound of formula (I), which comprises an ortho-substituted phenyl ring that may be further substituted with up to four additional substituents (R1 which may include C1-4alkyl, O-C1-4alkyl, and halogens), and formula (I) may further comprise (i) additional substituents R3 and R3’ which may include hydrogen an C1-3alkyl; (ii) additional substituent R2 which may include C1-4alkyl, and -(CH2CH2O)s-CH3- wherein s is an integer from 1 to 10; and (iii) L which may be any cleavable linker. Furthermore, it is noted that with regard to D-NH- of instant claim 1, while the core structure is the same, there are multiple, highly variable structural groups (i.e., R10, R20, R30, R40, R50, X10, X20, Ya, Yb, Ring A10, and Ring B10) which may be further substituted themselves. It is noted that Applicant’s arguments of unexpected results are only drawn to a single possible ADC comprised within the genus of claim 1, and said single ADC is not considered to be sufficiently representative of the instantly claimed genus in view of the high degree of structural variability; data from a single representative ADC is not sufficient to establish that all, or even most, members of the instantly claimed genus would possess the same characteristics and exhibit the same results.
Thus, in view of the above, the rejection of claims 1, 3-5, 7, 10-14, 41-44, and 46 under 35 U.S.C. 103 over Bruml, Vyskocil, Gallery, Raje, Mizori, Pasut, and Gonzalez is maintained, and the rejection of new claims 47-50 under 35 U.S.C. 103 over Bruml, Vyskocil, Gallery, Raje, Mizori, Pasut, and Gonzalez is deemed proper.
Double Patenting - Withdrawn
Claims 15-16 and 45 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 14, and 17-18 of U.S. Patent No. 12,221,460 (herein after referred to as “fist reference patent”) in view of non-patent literature by Gallery et. al. (PLOS ONE, 2018, 13(1), 1-20; herein after referred to as "Gallery") and WO 2019/092660 A1 (herein after referred to as "Vyskocil").
Claims 15-16 and 45 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 14 of U.S. Patent No. 11,725,024 (herein after referred to as “second reference patent”) in view of non-patent literature by Gallery et. al. (PLOS ONE, 2018, 13(1), 1-20; herein after referred to as "Gallery") and WO 2019/092660 A1 (herein after referred to as "Vyskocil").
Claims 15-16 and 45 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 36-37, 40-53, and 55 of copending Application No. 19/005,330 (herein after referred to as “reference application”).
It is noted that claims 15-16 and 45 have been cancelled, rendering their rejection moot. As such, the above-listed rejections of claims 15-16 and 45 under nonstatutory double patenting are withdrawn.
Double Patenting - Updated as Necessitated by Amendment
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, 3-5, 7, 10-14, 41-44, and 46 stand as rejected, and new claims 47-50 are newly rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 14, and 17-18 of U.S. Patent No. 12,221,460 (herein after referred to as “fist reference patent”) in view of non-patent literature by Gallery et. al. (PLOS ONE, 2018, 13(1), 1-20; herein after referred to as "Gallery") and WO 2019/092660 A1 (herein after referred to as "Vyskocil").
PNG
media_image14.png
152
342
media_image14.png
Greyscale
The claims of the first reference patent are drawn to (i) a method of treating cancer in a subject in need thereof generally comprising administering a compound (claims 1-7 and 14); (ii) a method of stimulating an immune response in a subject in need thereof generally comprising administering a compound (claim 17); and (iii) a method of preparing a compound wherein the compound of methods (i)-(iii) is of the Formula below:
As such, the claims are also drawn to the compound itself. All of the substituents are generally defined by independent claims 1, 17, and 18, and dependent claims 2-6 further define the individual substituents and claim 7 provides a full structure denoted as Formula (VI), shown below, and claim 14 discloses cancers that can be treated by said compound.
PNG
media_image15.png
342
812
media_image15.png
Greyscale
Therefore, it is specifically noted that Formula (VI) of the first reference patent reads on the instant formulas presented in instant claims 1, 3-5, 7, 10-16, and 42-45. However, it is noted that the first reference patent does not specifically teach an anti-GCC antibody nor the specific STING agonist as instantly claimed. This deficiency is remedied by Gallery and Vyskocil.
Gallery teaches that Guanylyl cyclase C (GCC) is a cell-surface protein that is expressed by normal intestinal epithelial cells, more than 95% of metastatic colorectal cancers (mCRC), and the majority of gastric and pancreatic cancers; due to strict apical localization, systemically delivered GCC-targeting agents should not reach GCC in normal intestinal tissue, while accessing antigen in tumor (Abstract). The authors generated an investigational antibody-drug conjugate (TAK-264, formerly MLN0264) comprising a fully human anti-GCC monoclonal antibody conjugated to monomethyl auristatin E via a protease-cleavable peptide linker (Id.). TAK-264 was cytotoxic in vitro and in vivo to GCC-expressing cells, providing a solid scientific rationale for further preclinical and clinical development of this drug; as GCC is a highly specific colon epithelial antigen that is expressed on both primary and metastatic CRC tumors as well as gastric, esophageal, and pancreatic tumors, TAK-264 may provide a novel targeted approach for the treatment of these GCC-expressing malignancies, which are diseases of unmet medical need (Page 16, Paragraph 2).
PNG
media_image7.png
740
728
media_image7.png
Greyscale
Vyskocil teaches a novel compound of Formula (I), shown below, having a STING agonistic activity, which can be useful as an agent for the treatment of cancer and other diseases (Paragraphs 0004-0005).
More specifically, Vyskocil teaches an exemplary structure for a compound of Formula (I) having the structure shown below (designated by Vyskocil as Formulas I-5a, I-5b, I-5c, and I-5d; see Page 32).
PNG
media_image8.png
222
310
media_image8.png
Greyscale
Thus, Vyskocil teaches the D-NH- component (the above structure is the corresponding D-NH2 formula) of the instant invention.
The first reference patent, Galley, and Vyskocil are considered to be analogous to the present invention as they are in the same field of antibody-drug conjugates, which are useful in treating cancer, and/or STING agonists. Thus, it would have been obvious to one of ordinary skill in the art to combine prior art elements according to known methods which would be expected to yield predictable results. The first reference patent teaches STING-agonist ADCs wherein the linker of said ADCs are comprised of one or more linker components including self-immolative groups, amino acids (one, two, or more), and PEG groups (see, for example, pages 1-3 and 209-216) and Gallery teaches anti-GCC antibodies in ADCs for the treatment of GCC-expressing cancer (see entire document). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Thus, modifying the ADC of the first reference patent to comprise an anti-GCC antibody and a specific STING agonist would be expected to yield an ADC capable of being used for the same purpose (e.g., treating cancer).
PNG
media_image11.png
96
141
media_image11.png
Greyscale
The structure of Formula (VI) of the first reference patent thus corresponds to Formula (I) of instant claim 1 wherein: a=1, b=1, m=0, n=0, R1 is absent (m=0), R2 is C1 alkyl, R3 and R3’ are both H, L is a cleavable linker (i.e., comprises two self-immolative groups, a cleavable Ala-Val peptide, and mPEG8/maleimide functionalized Lys), Ab is an anti-GCC antibody, and D-NH is an amino-substituted compound (i.e., a STING agonist) wherein Ring A10 is a 5-membered monocyclic heteroaryl ring containing 2 heteroatoms that are N, Ring B10 is a 9-membered bicyclic heteroaryl ring comprising 4 heteroatoms that are N further substituted with O (i.e., C=O), X10 and X20 are each SH, R30, R40, and R50 are each hydrogen, on of R10 and R20 is hydrogen and the other is OH, and Ya and Yb are each O. Thus, ADC rendered obvious above further reads on new claims 47-50. Notably, a=1, b=1, m=0, W is the structure shown below, Z is cathepsin cleavable (i.e., the Val-Ala dipeptide is recognized by cathepsin), and a compound shown below wherein said compound is the D-NH-Linker compound that may be conjugated to an antibody via the maleimide group.
PNG
media_image12.png
199
449
media_image12.png
Greyscale
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-5, 7, 10-14, 41-45, and 46 stand as rejected, and new claims 47-50 are newly rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 14 of U.S. Patent No. 11,725,024 (herein after referred to as “second reference patent”) in view of non-patent literature by Gallery et. al. (PLOS ONE, 2018, 13(1), 1-20; herein after referred to as "Gallery") and WO 2019/092660 A1 (herein after referred to as "Vyskocil").
PNG
media_image16.png
156
402
media_image16.png
Greyscale
The claims of the second reference patent are drawn to a compound of the Formula below, and a pharmaceutical composition thereof:
All of the substituents are generally defined by independent claim 1, and dependent claims 2-6 further define the individual substituents and claim 7 provides a full structure denoted as Formula (VI), shown below.
PNG
media_image17.png
564
1392
media_image17.png
Greyscale
Furthermore, it is noted that the specification further discloses uses for compounds of the invention, including in the treatment of cancer and stimulating an immune response (Columns 16-17) each of which comprise the administration of a compound of the invention. The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). See MPEP 804(II)(B)(1).
As such, it is specifically noted that Formula (VI) of the second reference patent, and the uses of such a compound as disclosed in the specification, read on instant claims 1, 3-5, 7, 10-16, and 42-45. However, it is noted that the second reference patent does not specifically teach an anti-GCC antibody nor the specific STING agonist as instantly claimed. This deficiency is remedied by Gallery and Vyskocil.
Gallery teaches that Guanylyl cyclase C (GCC) is a cell-surface protein that is expressed by normal intestinal epithelial cells, more than 95% of metastatic colorectal cancers (mCRC), and the majority of gastric and pancreatic cancers; due to strict apical localization, systemically delivered GCC-targeting agents should not reach GCC in normal intestinal tissue, while accessing antigen in tumor (Abstract). The authors generated an investigational antibody-drug conjugate (TAK-264, formerly MLN0264) comprising a fully human anti-GCC monoclonal antibody conjugated to monomethyl auristatin E via a protease-cleavable peptide linker (Id.). TAK-264 was cytotoxic in vitro and in vivo to GCC-expressing cells, providing a solid scientific rationale for further preclinical and clinical development of this drug; as GCC is a highly specific colon epithelial antigen that is expressed on both primary and metastatic CRC tumors as well as gastric, esophageal, and pancreatic tumors, TAK-264 may provide a novel targeted approach for the treatment of these GCC-expressing malignancies, which are diseases of unmet medical need (Page 16, Paragraph 2).
Vyskocil teaches a novel compound of Formula (I), shown below, having a STING agonistic activity, which can be useful as an agent for the treatment of cancer and other diseases (Paragraphs 0004-0005).
PNG
media_image7.png
740
728
media_image7.png
Greyscale
More specifically, Vyskocil teaches an exemplary structure for a compound of Formula (I) having the structure shown below (designated by Vyskocil as Formulas I-5a, I-5b, I-5c, and I-5d; see Page 32).
PNG
media_image8.png
222
310
media_image8.png
Greyscale
Thus, Vyskocil teaches the D-NH- component (the above structure is the corresponding D-NH2 formula) of the instant invention.
The second reference patent, Galley, and Vyskocil are considered to be analogous to the present invention as they are in the same field of antibody-drug conjugates, which are useful in treating cancer, and/or STING agonists. Thus, it would have been obvious to one of ordinary skill in the art to combine prior art elements according to known methods which would be expected to yield predictable results. The second reference patent teaches STING-agonist ADCs wherein the linker of said ADCs are comprised of one or more linker components including self-immolative groups, amino acids (one, two, or more), and PEG groups (see, for example, pages 1-3 and 209-216) and Gallery teaches anti-GCC antibodies in ADCs for the treatment of GCC-expressing cancer (see entire document). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Thus, modifying the ADC of the second reference patent to comprise an anti-GCC antibody and a specific STING agonist would be expected to yield an ADC capable of being used for the same purpose (e.g., treating cancer).
The structure of Formula (VI) of the first reference patent thus corresponds to Formula (I) of instant claim 1 wherein: a=1, b=1, m=0, n=0, R1 is absent (m=0), R2 is C1 alkyl, R3 and R3’ are both H, L is a cleavable linker (i.e., comprises two self-immolative groups, a cleavable Ala-Val peptide, and mPEG8/maleimide functionalized Lys), Ab is an anti-GCC antibody, and D-NH is an amino-substituted compound (i.e., a STING agonist) wherein Ring A10 is a 5-membered monocyclic heteroaryl ring containing 2 heteroatoms that are N, Ring B10 is a 9-membered bicyclic heteroaryl ring comprising 4 heteroatoms that are N further substituted with O (i.e., C=O), X10 and X20 are each SH, R30, R40, and R50 are each hydrogen, on of R10 and R20 is hydrogen and the other is OH, and Ya and Yb are each O. Thus, ADC rendered obvious above further reads on new claims 47-50. Notably, a=1, b=1, m=0, W is the structure shown below, Z is cathepsin cleavable (i.e., the Val-Ala dipeptide is recognized by cathepsin), and a compound shown below wherein said compound is the D-NH-Linker compound that may be conjugated to
PNG
media_image11.png
96
141
media_image11.png
Greyscale
an antibody via the maleimide group.
PNG
media_image12.png
199
449
media_image12.png
Greyscale
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-5, 7, 10-14, 41-44, and 46 stand as provisionally rejected, and new claims 47-50 are newly provisionally rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 36-37, 40-53, and 55 of copending Application No. 19/005,330 (herein after referred to as “reference application”).
PNG
media_image18.png
108
128
media_image18.png
Greyscale
The claims of the reference application are drawn to (i) a compound of Formula (I), shown below; (ii) a pharmaceutical composition thereof; (iii) a method of treating cancer thereof; and (iv) a method of stimulating an immune response thereof.
PNG
media_image19.png
140
234
media_image19.png
Greyscale
Of particular note is the more specific structure of Formula (Ia) defined by dependent claim 40, shown below.
All of the substituents are generally defined by independent claim 36 and/or dependent claims 37 and 40-51 further define the individual substituents. The reference application discloses the following: claim 40 discloses the general structure of instant claim 1; claim 41 discloses a, b, and m values; claim 42 discloses a more specific linker structure; and claims 43-51 disclose structural components of the linker and respective substituents.
The reference application is considered to be analogous to the present invention as they are in the same field of STING modulating conjugates. While no full structure is provided in the claims of the reference application, the possible structures of D and L (and their respective substituents) are disclosed by the claims of the reference patent read on and suggest possible structures that read on the structures of instant claims 1, 3-5, 7, 10-16, and 42-45. However, the reference application does not disclose an anti-GCC antibody nor the instantly claimed STING agonist. However, these deficiencies are remedied by Gallery and Vyskocil.
Gallery teaches that Guanylyl cyclase C (GCC) is a cell-surface protein that is expressed by normal intestinal epithelial cells, more than 95% of metastatic colorectal cancers (mCRC), and the majority of gastric and pancreatic cancers; due to strict apical localization, systemically delivered GCC-targeting agents should not reach GCC in normal intestinal tissue, while accessing antigen in tumor (Abstract). The authors generated an investigational antibody-drug conjugate (TAK-264, formerly MLN0264) comprising a fully human anti-GCC monoclonal antibody conjugated to monomethyl auristatin E via a protease-cleavable peptide linker (Id.). TAK-264 was cytotoxic in vitro and in vivo to GCC-expressing cells, providing a solid scientific rationale for further preclinical and clinical development of this drug; as GCC is a highly specific colon epithelial antigen that is expressed on both primary and metastatic CRC tumors as well as gastric, esophageal, and pancreatic tumors, TAK-264 may provide a novel targeted approach for the treatment of these GCC-expressing malignancies, which are diseases of unmet medical need (Page 16, Paragraph 2).
Vyskocil teaches a novel compound of Formula (I), shown below, having a STING agonistic activity, which can be useful as an agent for the treatment of cancer and other diseases (Paragraphs 0004-0005).
PNG
media_image7.png
740
728
media_image7.png
Greyscale
More specifically, Vyskocil teaches an exemplary structure for a compound of Formula (I) having the structure shown below (designated by Vyskocil as Formulas I-5a, I-5b, I-5c, and I-5d; see Page 32).
PNG
media_image8.png
222
310
media_image8.png
Greyscale
Thus, Vyskocil teaches the D-NH- component (the above structure is the corresponding D-NH2 formula) of the instant invention.
The reference application, Galley, and Vyskocil are considered to be analogous to the present invention as they are in the same field of antibody-drug conjugates, which are useful in treating cancer, and/or STING agonists. Thus, it would have been obvious to one of ordinary skill in the art to combine prior art elements according to known methods which would be expected to yield predictable results. The reference application teaches STING-agonist ADCs wherein the linker of said ADCs are comprised of one or more linker components including self-immolative groups, amino acids (one, two, or more), and PEG groups (see, for example, pages 1-3 and 209-216) and Gallery teaches anti-GCC antibodies in ADCs for the treatment of GCC-expressing cancer (see entire document). “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). Thus, modifying the ADC of the reference application to comprise an anti-GCC antibody and a specific STING agonist would be expected to yield an ADC capable of being used for the same purpose (e.g., treating cancer).
PNG
media_image11.png
96
141
media_image11.png
Greyscale
The claims of the reference application read on Formula (I) of instant claim 1 wherein: a=1, b=1, m=0, n=0, R1 is absent (m=0), R2 is C1 alkyl, R3 and R3’ are both H, L is a cleavable linker (i.e., comprises two self-immolative groups, a cleavable Ala-Val peptide, and mPEG8/maleimide functionalized Lys), Ab is an anti-GCC antibody, and D-NH is an amino-substituted compound (i.e., a STING agonist) wherein Ring A10 is a 5-membered monocyclic heteroaryl ring containing 2 heteroatoms that are N, Ring B10 is a 9-membered bicyclic heteroaryl ring comprising 4 heteroatoms that are N further substituted with O (i.e., C=O), X10 and X20 are each SH, R30, R40, and R50 are each hydrogen, on of R10 and R20 is hydrogen and the other is OH, and Ya and Yb are each O. Thus, ADC rendered obvious above further reads on new claims 47-50. Notably, a=1, b=1, m=0, W is the structure shown below, Z is cathepsin cleavable (i.e., the Val-Ala dipeptide is recognized by cathepsin), and a compound shown below wherein said compound is the D-NH-Linker compound that may be conjugated to an antibody via the maleimide group.
PNG
media_image12.png
199
449
media_image12.png
Greyscale
This is a provisional nonstatutory double patenting rejection.
With regard to the claim rejections under nonstatutory double patenting, on Pages 26-27 of Remarks Applicant has requested the claim rejections over the ‘460 patent (i.e., first reference patent), the ‘024 patent (i.e., second reference patent), and the copending ‘330 application (i.e., reference application) be held in abeyance until allowable subject matter is identified in the present application. As such, the above-listed rejections of claims 1, 3-5, 7, 10-14, 41-44, and 46 are maintained and the rejections of new claims 47-50 are deemed proper.
Conclusion
Claims 1, 3-5, 7, 10-14, 41-44, and 46-50 are pending. Claims 1, 3-5, 7, 10-14, 41-44, and 46-50 are rejected. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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, Samira Jean-Louis can be reached at (571)270-3503. 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.
/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642