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 .
Status of claims
Claims 25-28 are pending and under consideration.
Withdrawn Rejections
The rejection of claim 28 under 35 U.S.C. 112 (a) is withdrawn in view of the claim amendment.
Maintained Rejection with changes per claim Amendment
Claim Rejections - 35 USC § 103
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 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 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 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Howard et al. (WO 2011/130598) (cited on the IDS of 10/10/2022) in view of Clingen et al. Nucleic Acids Res. 2005 Jun 8;33(10):3283-91.
Regarding claim 25-26, Howard (page 138, Scheme 4) teaches a conjugate, comprising pyrrolobenzodiazepines (PBDs) complex which has the following structure, wherein R10 and R11
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form a nitrogen-carbon double bond, as described in the instant claim. Howard (page 134) discloses LB moiety linker is the same as LN and has the following structure:
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The asterisk and wavy line indicate the point of attachment, leading to compound 15d, comparable to the instant claim.
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Howard (page 103) also teaches the following regarding the compound stereochemistry:
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While compound 15d has a
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diether linkage (at n= 1, which forms a pentane bridge), which differs to that of the instant claim (at n= 0, which forms a propane bridge). However, Howard (page 80) teaches that length of the diether linkage can vary, meaning the alkane can either be pentane or propane bridge. For example, Howard (page 80) teaches alkane
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chain inside square bracket [ ] with subscript n can either be 1 or 0. Thus, when n= 0, the alkane unit is absent or no repetition; suggesting the linker would be n-propane instead of pentane bridge at n= 1, identical to the instant claim. Therefore, to a person of ordinary skill in the art (POSITA) would understand that incorporating the optional alkane chains would provide a versatile strategy to fine tune the mechanical and chemical properties of the polymer. This is supported by Clingen (page 3284) discloses a PDB compound SJG-136 having a propane diether linkage. Therefore, it would have been obvious for a POSITA to consider alkane chain variation
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as a key optimization strategy, to arrive at the claimed invention, because n is either 1 or 0 which provides the ability to fine-tune the polymer diether linkage.
Regarding claim 27, Howard (231, claim 72), as applied to claims 25-26 above, teaches a PBP compound comprising the following structure, which is comparable to the instant claim.
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Howard’s compound differs from the instant claim from one another in that Howard’s compound has an ethylene oxide repeat of unit
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, whereas the instant claim discloses
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. Howard clearly discloses the same compound that differs only on the arrangement of the ethylene oxide repeat unit. In fact, as observed in the 103 rejection above, Howard clearly teaches both arrangements, even the specific fragment -CH2CH2-[OCH2CH2]n-, as presented in compound 15d, suggesting alternative orientation of the same monomeric fragments when n= 8, without introducing unpredictability. Given that Howard already discloses the claimed structural analogs; thus, it would have been obvious to a POSITA to interchange or select among these closely related units to arrive at the claimed invention, because of Howard’s teachings provide such option.
Regarding claim 28, Howard (page 222, claim 46) teaches the following:
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Therefore, it would have been obvious to a POSITA to recognize that the antibody is the ligand, (L-D)р and (DL)p are the PDB drug moiety; thus, despite their different representations, both formulas are equivalent. Howard (page 225, claim 54), as applied to claim 25-27, also discloses an antibody-drug conjugate based on the formula above, with the following structure:
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Howard (page 77, line 16-25) explains the antibody connects to a PDB drug moiety via a thiol group, which serves as conjugation sites to form a thioether bond with the maleimide moiety. While the instant claim does not display the thioether bond, however, the specification (page 89, line 21-23) teaches the expected presence of a thioether that would connect the ligand to the PDB drug moiety:
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Therefore, a POSITA would have had a reasonable expectation of success before the effective filing date of the claimed invention to combine the teachings of Howard in view of Clingen to arrive at the claimed invention, because Howard clearly teaches a comparable compound and the method of connecting an antibody agent to the PDB drug moiety, as indicated above.
Maintained Rejection
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 25-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-3 of U.S. Patent No. US 11517626 in view of Howard et al. (WO 2011/130598).
Although the claims at issue are not identical, they are not patentably distinct from each
other because compounds claimed in US patent ‘626 are comparable to those of the instant
claims. Regarding claim 2 of the US patent ‘626 a conjugate comprising the following structure, reading on instant claim 25-26. US patent ‘626 differs from the instant claim
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from one another in that US patent ‘626 compound presents a maleimide functional group as the attachment site for conjugation with a cell binding agent, which is not presented in the instant claims 25-26. However, instant claim 28 in view of Howard discloses a conjugate compound in which maleimide serves as the attachment point for a cell binding agent, comparable to US patent ‘626. Given that maleimide is wildly-used as an attachment site for linking ligands to
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polymers, thus, it would have been obvious to a POSITA to modify the instant claim into a conjugate compound.
Claim 3 of US patent ‘626 teaches a conjugate compound with a comparable structure
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to that of the instant claim 27. Therefore, it would have been obvious to a POSITA to modify the instant claim into a conjugate compound, using the maleimide functional group as the attachment site for conjugation with a cell binding agent.
Given the claimed compound of the instant claim comparable to that of and US patent ‘626 without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term.
Response to Argument
Applicant argues that the 103 rejection is improper in view of Gregson, because Gregson teaches that compound 4d (pentylene bridge) is more cytotoxic than compound 4a (propylene bridge). Applicant then argues that a POSITA would therefore have selected a pentylene spacer over propylene. Applicant’s argument is not persuasive because Gregson does not explicitly teach away from propylene by indicating that such linker is unsuitable or inoperative. Although 4b is reported as more potent than 4a, Gregson also reported that both 4a and 4b are also superior than analogs (compound 3a-c), demonstrating routine optimization. Not to mention that Gregson never explicitly indicates that propylene linkers are inferior in manner that would discourage their use in the art. It is also important to highlight that cytotoxicity only measure how toxic a compound is to cells, which does not take into consideration the compound stability, selectivity, therapeutic index and pharmacokinetics. Thus, higher cytotoxicity does not necessarily equivalent to overall best, because often less toxic compound often produces less side effects and safer dosing. It is important to highlight that Howard (page 80), as disclosed in the 103 rejection above, teaches alkane chain between the PDB subunits can either be propylene or pentylene bridge, thus a POSITA would not consider Gregson’ disclosure as a teaching away, but rather as a design variable.
Applicant argues that the Affidavit by Dr. Luke Masterson establishes that the claimed compound is 15x more potent than compound 15d of Howard. Applicant’s argument is not persuasive because this comparison is improper and insufficient because it fails to properly account for the entirety of Howard’s teachings. The affidavit only compares the claimed compound only against the PDB complex containing a pentylene bridge, while entirely omitting comparison to the propylene bridge as taught by Howard. This is a selective comparison and is improper because Howard (page 80) teaches that length of the diether linkage between the PDB can either be pentylene or propylene bridge. For example, Howard (page 80) teaches alkane
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chain inside square bracket [ ] with subscript n can either be 1 or 0. Thus, when n= 0, the alkane unit is absent or no repetition; suggesting the linker would be propylene instead of pentylene bridge at n= 1, identical to the instant claim. Therefore, the affidavit clearly fails to compare the full scope of Howard’s teaching which then weakens Applicant’s argument; thus, the rejection is maintained.
Conclusion
Therefore, claims 25-28 are rejected.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622