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 .
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 1-22 drawn to a peptide ligand specific for MT1-MMP) in the reply filed on April 17, 2024, is acknowledged. Additionally, Applicant’s election without traverse of SEQ ID NO: 57 as a peptide ligand thereby correlating to a first loop sequence of V[HArg]E and a second loop sequence of A[tBuAla]LFP[HArg]T in the reply filed on April 17, 2024, is acknowledged.
Please note that in light of the Examiner’s search, the species election is expanded to include SEQ ID NOs: 15-16.
Status of Claims
Claims 1-23 were originally filed on June 11, 2021.
The amendment received on December 15, 2021, amended claims 3-6, 8-16, 21, and 23. The amendment received on April 17, 2024, canceled claims 7, 13, 20, and 23; amended claims 2-6, 8-12, 14, and 16-19; and added new claims 24-25. The amendment received on September 23, 2024, amended claims 3-6 and 8-12. The amendment received on March 9, 2026, canceled claims 2-6 and 8-12; amended claims 1 and 14; and added new claims 26-31.
Claims 1, 14-19, 21-22, and 24-31 are currently pending and claims 1, 14-19, 21-22, 24-27, and 29-31 are under consideration as claim 28 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 17, 2024.
Priority
The present application claims status as a 371 (National Stage) of PCT/GB2019/053540 filed December 13, 2019, and claims priority under 119(a)-(d) to United Kingdom Application Nos. 1820286.1 filed on December 13, 2018, and 1906534.1 filed on May 9, 2019.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for United Kingdom Application Nos. 1820286.1 and 1906534.1, which papers have been placed of record in the file. Please note that the United Kingdom applications are in English and therefore no further action is necessary.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 9, 2026, is being considered by the examiner.
Sequence Interpretation
For claim 1, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to one of the claimed sequences with any N- and/or C-termini additions.
For claim 26, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to one of the claimed sequences with any N- and/or C-termini additions.
For claim 27, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 57 with any N- and/or C-termini additions.
Response to Arguments
Applicant’s arguments, see Response, filed 3/9/26, with respect to the claim objections have been fully considered and are persuasive. The objections of claims 1 and 14 have been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 112(a), written description, rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22 and 24-25 as failing to comply with the written description requirement has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-2, 15-19, 21-22, and 24-25 as being anticipated by Bennett et al. WO 2018/127699 A1 published on July 12, 2018 (cited in the IDS received on 11/3/23) has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-2 and 24 as being anticipated by Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1, 6, and 14 as being unpatentable over Bennett et al. WO 2018/127699 A1 published on July 12, 2018 (cited in the IDS received on 11/3/23) has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) has been withdrawn.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1-12 of U.S. Patent No. 10,532,106 B2 (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘106 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1-17 of U.S. Patent No. 10,994,019 B2 (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘019 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1-14 of U.S. Patent No. 10,792,368 B1 (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘368 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1-24 of U.S. Patent No. 11,103,591 B2 (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘591 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1-19 of U.S. Patent No. 11,672,868 B2 (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘868 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1-13 of U.S. Patent No. 12,318,454 B2 in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘454 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 1, 5-15, 17, and 19-20 of copending Application No. 17/309,629 (US Publication No. 2022/0072140 A1) (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014) and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘629 claimed invention.
Applicant’s arguments, see Response, filed 3/9/26, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 1-2, 14-19, 21-22, and 24-25 as being unpatentable over claims 42-53 of copending Application No. 19/197,288 (US Publication No. 2025/0255975 A1) (cited in the IDS received on 11/3/23) in view of Chen et al., Angew. Chem. Int. Ed. 53:1602-1606 (2014), Laxmi et al., Ind. J. Cancer 44:62-71 (2007), and Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23) has been withdrawn. Please note that none of the instant amino acid sequences in amended claim 1 are claimed in the ‘288 claimed invention.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 14-19, 21-22, 24-27, and 29-31 are rejected under 35 U.S.C. 103 as being obvious over Bennett et al. WO 2018/127699 A1 published on July 12, 2018 (cited in the IDS received on 11/3/23).
For claims 1 and 26-27, ‘699 teaches compounds that bind to the hemopexin domain of MT1-MMP where a specific compound with the structure:
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(See ‘699, [0037], [0080]). When comparing ‘699’s compound I-16 with instant SEQ ID NO: 15, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at positions 3 and 11. When comparing ‘699’s compound I-16 with instant SEQ ID NO: 16, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at position 3. When comparing ‘699’s compound I-16 with instant SEQ ID NO: 57, there is 100% identity except for where tBuAla is Leu, i.e., an extra CH2 in the side chain, at position 7. Pursuant to MPEP 2144.09(I), [a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). In the instant case, the only chemical distinctions between compound I-16 of ‘699 and instant SEQ ID NOs: 15-16 and 57 is either an added -CH2- chemical moiety in the side chain of each arginine residue (i.e., instant SEQ ID NO: 15), an added -CH2- chemical moiety in the side chain of one arginine residue (i.e., SEQ ID NO: 16), or a removed -CH2- chemical moiety in the side chain of tBuAla (i.e., SEQ ID NO: 57). However, an ordinary skilled artisan would expect instant SEQ ID NOs: 15-16 and 57 and ‘699’s compound I-16 to have similar properties. When chemical compounds have “very close” structural similarities and similar utilities, without more a prima facie case may be made. In re Wilder, 563 F.2d 457 (CCPA 1977)(MPEP 2144.09.II). Stated alternatively, obviousness may be based solely upon structural similarity (an established structural relationship between a prior art compound and the claimed compound, as with homologs). See In re Duel, 51 F.3d 1552, 1559 (Fed. Cir. 1995). The necessary motivation to make the claimed compound (i.e., removing a -CH2- in the side chain of one or both arginine residues or adding a -CH2- in the side chain of the leucine at position 7 in the polypeptide sequence), and thus the prima facie case of obviousness, arises from the reasonable expectation that compounds similar in structure have similar properties. In re Gyurik, 596 F.2d 1012, 1018 (CCPA 1979). Thus, the teachings of ‘699 render obvious a peptide ligand comprising SEQ ID NO: 15-16 or 57 as recited in instant claims 1 and 26-27.
Regarding that the peptide ligand is specific for MT1-MMP, although ‘699 discloses such function, it is unnecessary for ‘699 to expressly disclose this function because ‘699 discloses a compound comprising the required structural limitations as recited in instant claim 1. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
For claim 14, ‘699 teaches a composition comprising a compound of the invention, e.g., I-16, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle (‘699, [0121]). Pharmaceutically affectable salts are defined as those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio (‘699, [0122]). ‘699 also teaches that the pharmaceutically acceptable salts are well known in the art, and include alkali metal, alkaline earth metal, and ammonium salts (‘699, [0122]). Examples of alkali or alkaline earth metal salts include sodium, potassium, magnesium, calcium and lithium (‘699, [0123]).
Therefore, it would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant application to follow the teachings of ‘699 and formulate the compound in a composition as a pharmaceutically acceptable salt such as sodium, potassium, calcium or ammonium where the use of these salts are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. An ordinary skilled artisan would have been motivated to follow 699s’ teachings because formulating a peptide in a composition as a pharmaceutically acceptable salt such as a sodium, potassium, calcium or ammonium salt is a well-known technique, and therefore, using a well-known technique to yield predictable results (i.e., a peptide ligand of claim 1 formulated with a sodium, potassium, calcium or ammonium salt) is well within the purview of an ordinary skilled artisan. Thus, an ordinary skilled artisan would have been motivated with a reasonable expectation of success to formulate a peptide ligand comprising the structure of ‘699’s I-16 compound as a sodium, potassium, calcium or ammonium salt in order to formulate the peptide ligand suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio because formulating a peptide ligand as a pharmaceutically acceptable salt such as a sodium, potassium, calcium or ammonium salt constitutes the use of a known technique to improve similar devices (methods, or products) in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant to KSR.
For claim 15, ‘699 teaches that the polypeptide is specific for human, mouse and/or dog MT1-MMP (See ‘699, [0037]). Thus, the ‘699 disclosure satisfies the claim limitation with respect to where the MT1-MMP is human as recited in instant claim 15.
Additionally and/or alternatively, it is noted that the subject matter of claim 15 further limits the functional property of the peptide ligand, i.e., being specific for human MT1-MMP. As discussed supra, since ‘699 suggests a specific species of peptide ligand meeting all the required structural limitations, it would then necessarily follow that any function associated with the required structure is also met.
For claims 16-19, ‘699 teaches the compound I-16 depicted supra conjugated to one or more effector and/or functional groups where the one or more effector and/or functional groups is a cytotoxic agent of MMAE as compound I-16:
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(See ‘699, [0119]; Table 1b). As such, the peptide ligand specific for MT1-MMP is conjugated via a linker comprising -PABC-Cit-Val-Glutaryl- to MMAE as a cytotoxic agent thereby satisfying the claim limitations as recited in instant claims 16-19.
For claims 21 and 24, ‘699 teaches a composition comprising a compound of the invention, e.g., I-16, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle (‘699, [0121]). Thus, the teachings of ‘699 satisfy the claim limitations as recited in instant claims 21 and 24.
For claims 22 and 25, ‘699 teaches that additional therapeutic agents that are normally administered to treat a condition can also be present in the compositions of the invention (See ‘699, [00166]). Thus, the teachings of ‘699 satisfy the claim limitations as recited in instant claims 22 and 25.
For claims 29-31, ‘699 teaches a 177Lu-loaded N241 (i.e., compound I-1a) bicycle drug conjugate that demonstrates rapid tumor localization when injected IV into mice bearing MT1-positive tumor xenografts with levels as high as 15-20% injected dose per gram of tumor in less than 60 minutes (See ‘699, [0017]; Table 1a). These properties suggest that N241 may be a good delivery vehicle for cytotoxic payloads targeting MTI-positive tumor cells (See ‘699, [0017]). As such, the teachings of ‘699 suggest the claim limitations as recited in instant claims 29-31.
Therefore, it would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant application to follow the teachings of ‘699 and substitute compound I-16 instead of I-1a as the bicycle peptide ligand, which is similar in structure to instant SEQ ID NOs: 15-16 or 57 for the reasons set forth supra, in the bicycle conjugate comprising compound I-1a to a metal radioisotope of 177Lu in order to demonstrate cellular localization of the bicycle peptide ligand to cells bearing MT1. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because conjugating a bicycle peptide ligand of compound I-1a to 177Lu was known to demonstrate rapid tumor localization when injected IV into mice bearing MT1-positive tumor xenografts with levels as high as 15-20% injected dose per gram of tumor in less than 60 minutes as taught by ‘699. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that compound I-1a as a bicycle peptide ligand of ‘699 was conjugated to a metal radioisotope of 177Lu, and therefore, substituting compound I-16 instead of compound I-1a as the bicycle peptide ligand would support the rapid tumor localization when injected IV into mice bearing MT1-positive tumor xenografts by constituting the simple substitution of one known element for another to obtain predictable results pursuant to KSR.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 3/9/26 for claims 1, 14-19, 21-22, 24-27, and 29-31 have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s argument, i.e., there is no teaching or suggestion in the cited references that the specific amino acid sequences recited in claim 1 would have high potencies as depicted in Tables 2-3 in the specification and the accompanying Appendix, and no suggestion to modify Bennett’s compound I-16 in the specific ways needed to arrive at a peptide ligand falling inside the scope of the presently amended claims would lead to a peptide ligand with such high potencies, it is found unpersuasive. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as discussed in the rejection supra, Bennett expressly teaches bicycle compound I-16. Although it is acknowledged that Bennett’s compound I-16 is not identical to any compound instantly claimed, Bennett’s compound I-16 is structurally similar. As stated in the rejection supra, when comparing ‘699’s compound I-16 with instant SEQ ID NO: 15, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at positions 3 and 11. As such, Bennett’s compound I-16 has two extra CH2 moieties, i.e., arginine in instant SEQ ID NO: 15 and homo-arginine in Bennett’s compound I-16 at two positions. When comparing ‘699’s compound I-16 with instant SEQ ID NO: 16, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at position 3. As such, Bennett’s compound I-16 has one extra CH2 moiety, i.e., arginine in instant SEQ ID NO: 16 and homo-arginine in Bennett’s compound I-16 at one position. When comparing ‘699’s compound I-16 with instant SEQ ID NO: 57, there is 100% identity except for where tBuAla is Leu, i.e., an extra CH2 in the side chain, at position 7. As such, Bennett’s compound I-16 has one extra CH2 moiety, i.e., tBuAla in instant SEQ ID NO: 57 and Leu in Bennett’s compound I-16 at one position. As stated in the rejection supra, MPEP 2144.09(I) recognizes the situation where chemical compounds have very close structural similarities and similar utilities where such very close structural similarities and similar utilities render the chemical compounds obvious without evidence to the contrary. Given the very close structural similarities and similar utilities between Bennett’s compound I-16 and instant SEQ ID NOs: 15-16 and 57 as identified supra, a prima facie case of obviousness can be made. Therefore, contrary to Applicant’s argument, the fact that Bennett does not teach a specific compound as instantly claimed does not per se correlate to nonobvious.
Additionally, is it acknowledged that the claimed SEQ ID NOs exhibit a nanomolar Kd or Ki value against MT1-MMP as depicted in instant Tables 2-3 and the accompanying Appendix. Such data would then constitute the claimed peptide ligand exhibiting unexpected results, i.e., nanomolar Kd or Ki value against MT1-MMP. MPEP 716.02(b) states 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). See In re Blondel, 499 F.2d 1311, 1317, 182 USPQ 294, 298 (CCPA 1974) and In re Fouche, 439 F.2d 1237, 1241-42, 169 USPQ 429, 433 (CCPA 1971) for examples of cases where indirect comparative testing was found sufficient to rebut a prima facie case of obviousness. Similarly, the Federal Circuit found, “[t]o be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). In the instant case, given the very close structural similarities and similar utilities between Bennett’s compound I-16 and instant SEQ ID NOs: 15-16 and 57 as discussed supra renders the claimed peptide ligand prima facie obvious, Applicants need to demonstrate that Bennett’s compound I-16 does not exhibit similar Kd or Ki values against MT1-MMP. It does not appear that the Kd or Ki value against MT1-MMP has been determined for Bennett’s compound I-16. The values depicted in instant Tables 2-3 and the accompanying Appendix only provide the Kd or Ki values of the claimed compounds. Without a comparison between Bennett’s compound I-16 with instant SEQ ID NOs: 15-16 and 57 demonstrating a statistically significant difference in binding affinity to MT1-MMP, a determination on whether instant SEQ ID NOs: 15-16 and 57 exhibit unexpected results, and thus, overcome the prima facie case of obviousness over Bennett cannot be made.
In response to Applicant’s argument, i.e., the Examiner’s basis for the rejection relies on hindsight, it is found unpersuasive. It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, as discussed supra in response to Applicant’s first argument, the teachings of Bennett suggest a peptide ligand comprising an amino acid sequence that is very close structurally and exhibits similar utilities to the instantly claimed peptide ligand. More specifically, there are very close structural similarities and similar utilities between Bennett’s compound I-16 and instant SEQ ID NOs: 15-16 and 57. As such, the Examiner is relying on the teachings of Bennett, not the instant specification to find that Bennett’s compound I-16 renders instant SEQ ID NOs: 15-16 and 57 obvious. Thus, contrary to Applicant’s argument, the Examiner does not utilize improper hindsight in order to render the claimed invention obvious.
Accordingly, the rejection of claims 1, 14-19, 21-22, 24-27, and 29-31 is maintained as Applicants’ arguments are found unpersuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 6, 14-19, 21-22, and 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,624,968 B2 (cited in the IDS received on 11/3/23) in view of Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23).
‘968 claims a compound of formula I comprising a bicycle polypeptide specific for MT1-MMP comprising SEQ ID NO: 1 or 5 anchored by a molecular scaffold such as TBMB or TATA (i.e., L1-L3 are -C(O)CH2CH2- and Ring A is 1,3,5-triazinane), a spacer, a bivalent moiety, a linker, and a chemotherapeutic agent such as MMAE as a toxin (See ‘968, claims 1-23) thereby constituting the peptide ligand as recited in instant claims 1-2, 16-19. ‘968 also claims a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, adjuvant or vehicle (See ‘968, claim 17) thereby constituting instant claims 21 and 24-25.
However, ‘968 does not expressly claim where the peptide ligand comprises instant SEQ ID NOs: 15-16 as recited in instant claim 6, where the polypeptide is in the form of a free acid or pharmaceutically acceptable salt such as potassium, calcium, sodium, or ammonium as recited in instant claim 14, where the compound is specific for human MT1-MMP as recited in instant claim 15, and where the composition additionally comprises one or more therapeutic agents as recited in instant claim 22.
Regarding where the peptide ligand comprises instant SEQ ID NOs: 15-16 and 57, when comparing ‘968’s compound in claim 9 with instant SEQ ID NO: 15, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at positions 3 and 11. When comparing ‘968’s compound in claim 9 with instant SEQ ID NO: 16, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at position 3. When comparing ‘968’s compound in claim 9 with instant SEQ ID NO: 57, there is 100% identity except for where tBuAla is Leu, i.e., an extra CH2 in the side chain, at position 7. Pursuant to MPEP 2144.09(I), [a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). In the instant case, the only chemical distinctions between the compound of ‘968’s claim 9 and instant SEQ ID NOs: 15-16 and 57 is either an added -CH2- chemical moiety in the side chain of each arginine residue (i.e., instant SEQ ID NO: 15), an added -CH2- chemical moiety in the side chain of one arginine residue (i.e., SEQ ID NO: 16), or a removed -CH2- chemical moiety in the side chain of tBuAla (i.e., SEQ ID NO: 57). However, an ordinary skilled artisan would expect instant SEQ ID NOs: 15-16 and 57 and ‘968’s compound of claim 9 to have similar properties. When chemical compounds have “very close” structural similarities and similar utilities, without more a prima facie case may be made. In re Wilder, 563 F.2d 457 (CCPA 1977)(MPEP 2144.09.II). Stated alternatively, obviousness may be based solely upon structural similarity (an established structural relationship between a prior art compound and the claimed compound, as with homologs). See In re Duel, 51 F.3d 1552, 1559 (Fed. Cir. 1995). The necessary motivation to make the claimed compound (i.e., removing a -CH2- in the side chain of one or both arginine residues in the polypeptide sequence or adding a -CH2- in the side chain of the leucine at position 7 in the polypeptide sequence), and thus the prima facie case of obviousness, arises from the reasonable expectation that compounds similar in structure have similar properties. In re Gyurik, 596 F.2d 1012, 1018 (CCPA 1979).
Regarding the compound being specific for human MT1-MMP, although ‘968 does not expressly claim such function, it is unnecessary for ‘968 to expressly teach this function because ‘968 claims a peptide ligand comprising the required structural limitations as recited in instant claim 1. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Regarding where the polypeptide is in the form of a free acid or pharmaceutically acceptable salt such as potassium, calcium, sodium, or ammonium, it is noted that ‘968 claims a salt of the peptide ligand (See ‘968 claim 1). Please see discussion of ‘035 supra. Briefly, an ordinary skilled artisan would be motivated with a reasonable expectation of success to formulate the peptide ligand in the form of a potassium, calcium, sodium, or ammonium salt given that formulating peptide ligands specific for MT1-MMP in the form of these salts is well-known in the art.
Regarding where the composition comprises an additional therapeutic agent, please see discussion of ‘035 supra. An ordinary skilled artisan would be motivated with a reasonable expectation of success to co-administer an additional therapeutic agent such as an antibody or immunotherapeutic drug with a drug conjugate comprising DM1 in order to treat cancer given that such combination treatment was known in light of ‘035.
Thus, the ‘968 claimed invention is not patentably distinct from the instantly claimed invention.
Claims 1-2, 6, 14-19, 21-22, and 24-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,433,137 B2 (cited in the IDS received on 11/3/23) in view of Teufel et al. WO 2016/067035 A1 published on May 6, 2016 (cited in the IDS received on 11/3/23).
‘137 claims a method for treating cancer by administering compound of formula I comprising a bicycle polypeptide comprising SEQ ID NO: 1 or 5 anchored by a molecular scaffold such as TBMB or TATA (i.e., L1-L3 are -C(O)CH2CH2- and Ring A is 1,3,5-triazinane), a spacer, a bivalent moiety, a linker, and a chemotherapeutic agent such as MMAE as a toxin where the spacer, bivalent moiety and linker encompass PABC-Cit-Val-glutaryl (See ‘137, claims 1-28) thereby constituting the peptide ligand as recited in instant claims 1-2, 16-19.
However, ‘137 does not expressly claim where the peptide ligand comprises instant SEQ ID NOs: 15-16 as recited in instant claim 6, where the polypeptide is in the form of a free acid or pharmaceutically acceptable salt such as potassium, calcium, sodium, or ammonium as recited in instant claim 14, where the compound is specific for human MT1-MMP as recited in instant claims 1 and 15, a pharmaceutical composition comprising the peptide ligand of claim 1 or a drug conjugate of claim 16 in combination with one or more pharmaceutically acceptable excipients as recited in instant claims 21 and 24, and where the composition additionally comprises one or more therapeutic agents as recited in instant claims 22 and 25.
Regarding where the peptide ligand comprises instant SEQ ID NOs: 15-16, when comparing ‘137’s compound I-16 in claims 22 and 28 with instant SEQ ID NO: 15, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at positions 3 and 11. When comparing ‘137’s compound I-16 in claims 22 and 28 with instant SEQ ID NO: 16, there is 100% identity except for where arginine is homo-arginine, i.e., an extra CH2 in the side chain, at position 3. When comparing ‘137’s compound I-16 with instant SEQ ID NO: 57, there is 100% identity except for where tBuAla is Leu, i.e., an extra CH2 in the side chain, at position 7. Pursuant to MPEP 2144.09(I), [a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). In the instant case, the only chemical distinctions between the compound of ‘968’s claim 9 and instant SEQ ID NOs: 15-16 is either an added -CH2- chemical moiety in the side chain of each arginine residue (i.e., instant SEQ ID NO: 15), an added -CH2- chemical moiety in the side chain of one arginine residue (i.e., SEQ ID NO: 16), or a removed -CH2- chemical moiety in the side chain of tBuAla (i.e., SEQ ID NO: 57). However, an ordinary skilled artisan would expect instant SEQ ID NOs: 15-16 and 57 and ‘137’s compound I-16 in claims 22 and 28 to have similar properties. When chemical compounds have “very close” structural similarities and similar utilities, without more a prima facie case may be made. In re Wilder, 563 F.2d 457 (CCPA 1977)(MPEP 2144.09.II). Stated alternatively, obviousness may be based solely upon structural similarity (an established structural relationship between a prior art compound and the claimed compound, as with homologs). See In re Duel, 51 F.3d 1552, 1559 (Fed. Cir. 1995). The necessary motivation to make the claimed compound (i.e., removing a -CH2- in the side chain of one or both arginine residues in the polypeptide sequence or adding a -CH2- in the side chain of the leucine at position 7 in the polypeptide sequence), and thus the prima facie case of obviousness, arises from the reasonable expectation that compounds similar in structure have similar properties. In re Gyurik, 596 F.2d 1012, 1018 (CCPA 1979).
Regarding the compound being specific for human MT1-MMP, although ‘137 does not expressly claim such function, it is unnecessary for ‘137 to expressly teach this function because ‘137 claims a peptide ligand comprising the required structural limitations as recited in instant claim 1. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Regarding where the polypeptide is in the form of a free acid or pharmaceutically acceptable salt such as potassium, calcium, sodium, or ammonium, it is noted that ‘137 claims a salt of the peptide ligand (See ‘137 claims 1, 14-15, and 28). Please see discussion of ‘035 supra. Briefly, an ordinary skilled artisan would be motivated with a reasonable expectation of success to formulate the peptide ligand in the form of a potassium, calcium, sodium, or ammonium salt given that formulating peptide ligands specific for MT1-MMP in the form of these salts is well-known in the art.
Regarding where a pharmaceutical composition comprises the peptide ligand of claim 1 or drug conjugate of claim 16 in combination with a pharmaceutically acceptable carrier and an additional therapeutic agent, please see discussion of ‘035 supra. An ordinary skilled artisan would be motivated with a reasonable expectation of success to co-administer an additional therapeutic agent such as an antibody or immunotherapeutic drug with pharmaceutical composition comprising a drug conjugate comprising DM1 in combination with a pharmaceutically acceptable carrier in order to treat cancer given that such combination treatment was known in light of ‘035.
Thus, the ‘137 claimed invention is not patentably distinct from the instantly claimed invention.
Applicants’ Arguments
Applicants respectfully request that the present double-patenting rejections be held in abeyance until the scope of allowable subject matter is determined (See Applicants Response received on 3/9/26, pg. 27-28).
Response to Arguments
Applicant’s request to hold the present double-patenting rejections be held in abeyance until the scope of allowable subject matter is determined is acknowledged. As such, the double-patenting rejections are maintained.
Conclusion
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.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654