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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/11/2026 has been entered.
Claim Status
Claims 1-47 have been cancelled and claim 92 has been amended, as requested in the amendment filed on 04/27/2026. Following the amendment, claims 48-93 are pending in the instant application.
Claims 55-58, 64-70, and 72-82 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or non-elected species of invention in the Response filed 08/23/2024, there being no allowable generic or linking claim.
Claims 48-54, 59-63, 71, and 83-93 are under examination in the instant office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claims 48-54, 59-63, 71, and 83-93 have an effective filing date of October 12, 2018 corresponding to PCT/CN2018/110155.
Claim Objections - Withdrawn
Claim 92 was objected to for a minor informality regarding a typographical error. Applicant has amended claim 92 to correct the typographical error. The objection to claim 92 is withdrawn, as noted in the previous Office Action (Advisory Action dated 05/01/2026).
Claim Rejections - 35 USC § 112 - Maintained
Claims 48-54, 59-63, 71, and 83-93 stand as rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite.
Response to Arguments - 35 USC § 112
It is noted that Applicant has not presented any arguments against the maintained claim rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
The arguments presented by Applicant previously in the Response After Final Action (04/27/2026) were found not persuasive and were addressed in the previous Office Action (Advisory Action dated 05/01/2026), as reproduced below for convenience.
Applicant argues that the Office's position regarding the broadest reasonable interpretation of "absent" in the claims is improper as it is (i) inconsistent with the specification (citing MPEP 2111) and (ii) inconsistent with the interpretation one of ordinary skill in the chemical art would reach. With regard to argument (i), it is noted that "[t]hough understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment." Superguide Corp. V. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004). See MPEP 2111.01. Additionally, the only exceptions to giving the words in a claim their ordinary and customary meaning in the art are (1) when the applicant acts as their own lexicographer; and (2) when the applicant disavows or disclaims the full scope of a claim term in the specification. To act as their own lexicographer, the applicant must clearly set forth a special definition of a claim term in the specification that differs from the plain and ordinary meaning it would otherwise possess. CCS Fitness, Inc. V. Brunswick Corp., 288 F .3d 1359, 1366, 62 USPQ2d 1658, 1662 (Fed. Cir. 2002). See MPEP 2111.01(III-IV). Without a special definition of "absent" in the instant specification, the broadest reasonable interpretation of the term to one of ordinary skill in the art (i.e., a chemist) must be applied. The term "absent" as would be applied under the broadest reasonable interpretation in a chemical context is that: when "absent", the functional group required for the sharing of elections to form a covalent bond (e.g., with adjacent functional groups) is no longer present, and as such electrons are no longer shared and the covalent bond(s) no longer exist. Such an interpretation is supported by the instant claims and specification, wherein it is noted that the substituent groups that may be absent are not all defined the same, and as such when one substituent group is removed the remaining adjacent substituents do not necessarily comprise the functional groups required to form a new covalent bond in place of bonds formed by the now absent substituent group. Specifically, it is noted that claim 48 indicates that Y1, Y2, Z1, and Z2 are "independently a function group that link a cell binding molecule Q, or Drug1 or Drug2, in a form of a disulfide, ether, ester…”. Thus, the claims themselves indicate that Y1 and Y2 are necessary to form a bond with Drug1 and Drug2, respectively, and Z1 and/or Z2 are required to form a bond with Q; as such it is maintained that the recitation in claim 48 that "Y1, Y2, R1, R2, R3, R4, Z1 or Z2 can be independently absent, provided that Y1, Y2, R1, R2, R3, R4, Z1 and Z2 may not be absent at the same time" is interpreted, under the broadest reasonable interpretation, such that any combination of the above listed substituents can be absent, so long as not all of the substituents are absent. For example, Y1, Y2, R1, R2, R3, R4, and Z1 can all be absent at the same time, so long as Z2 is still present; if Y1 and Y2 are absent at the same time, the conjugate would not comprise a drug and, in the same respect, if Z1 and Z2 were absent the conjugate would not comprise a cell-binding agent. Relying on exemplary structures throughout the specification, which include all substituent groups, and the intended meaning of "absent" does not negate the broadest reasonable interpretation. With regard to point (ii), the broadest reasonable interpretation of the term to one of ordinary skill in the art (i.e., a chemist) would arrive at absent any special definition of the term "absent" is provided above. Relying on other patent references to establish broadest reasonable interpretation when the fact patterns of the prior art are not the same as the instant case is improper, as the individual fact patterns of each reference establish the broadest reasonable interpretation for each respective reference. It is therefore maintained that the previously identified claim limitation as currently worded allows for structures that frustrate the purpose of the invention. Thus, the rejection of claims 48-54, 59-63, 71 and 83 -93 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is maintained.
Claim Rejections - 35 USC § 103 - Maintained
Claims 48-54, 59-63, 71 and 83-93 stand as rejected under 35 U.S.C. 103 as obvious over WO 2018/185526 Al (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as "Levengood").
Response to Arguments - 35 USC § 103
It is noted that Applicant has not presented any arguments against the maintained claim rejections under 35 U.S.C. 103.
The arguments presented by Applicant previously in the Response After Final Action (04/27/2026) were found not persuasive and were addressed in the previous Office Action (Advisory Action dated 05/01/2026), as reproduced below for convenience.
Applicant argues that the cytotoxic agent molecule of Zhao has two connecting sites each connected to one branch of the dual linker, wherein bis-linkage of the cytotoxic agent of Zhao via dual groups is more stable than mono-linked conjugates, and therefor Zhao teaches away from the proposed modification as adopting mono-linkages for would render Zhao unsatisfactory for its intended purpose, and the Office's interpretation of "absent" is inconsistent with the descriptions of Zhao which calls for cytotoxic agents having two connecting sites linked to the bis-linker. It is noted that the intended purpose of Zhao is to develop cytotoxin-cell binding molecule conjugates using a bis-linkage method. The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. 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); see also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent) ; In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); Ex parte Clapp, 227 USPQ 972 (Bd. Pat. App. & Inter. 1985) ( examiner must present convincing line of reasoning supporting rejection); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP 2144. Specifically, it is noted that Zhao suggests that the bis-linker of the invention comprises two functional groups, which may be the same or different, capable of reacting with a cytotoxic molecule ( simultaneously or sequentially). Levengood teaches conjugating more than one cytotoxic agent to an antibody wherein dual-drug ADCs demonstrated how delivery of multiple cytotoxic warheads can lead to improved ADC activities; the multi-drug ADCs of the study are active on cell types that are refractory to either of the individual component drugs, and highlights the potential for a new class of targeted therapeutics where multiple drugs with complementary or synergistic activities are simultaneously delivered. Thus, it would have been within the purview of one of ordinary skill in the art that for an ADC, one could select different, independently reactive groups for X and Y of Zhao wherein each could be sequentially reacted with a cytotoxic agent (sequential reactions with cytotoxic agents, i.e., single or multiple agents, are suggested by Zhao and Levengood, respectively) in order to (i) improve/increase drug loading and improve potency and/or (ii) load more than one kind of cytotoxic agent wherein complementary/synergistic cytotoxic agents in the same ADC molecule would further be expected to have improved activities (as supported by Levengood) because combining prior art elements according to known methods would be expected to yield predictable results with a reasonable expectation of success. Additionally, Applicant is reminded that preferred embodiments are not the only teaching of a reference. 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). With regard to the interpretation of "absent" in Zhao, it is noted that Zhao utilizes the same definitions as the instant application and does not provide a special definition of "absent"; further it is noted that as in the instant case, Zhao indicates that X and Y are, independently, function groups that link a cytotoxic drug via "a disulfide, thioether, thioester, peptide..." (see Page 4, Lines 25-28) wherein the only limitations are that "L1, L2, X, Y, Z1, and Z2 may be independently absent, but L1 and Z1, or L2 and Z2 may not be absent at the same time". Thus, the interpretation of absent as applied in the instant case is deemed proper for Zhao as well. Thus, the rejection of claims 48-54, 59-63, 71 and 83-93 under 35 U.S.C. 103 as being obvious over Zhao and Levengood is maintained.
Double Patenting - Maintained
Claims 48-54, 59-63, 71, and 83-93 stand as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the below listed copending Applications in view of WO 2018/185526 A1 (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as “Levengood”):
Claims 1, 5, 9, 11-13, 17-33, 36-42, 44, 46-51, 53, 55-59, and 63 of Application No. 16/488,764;
Claims 1-2, 4-20, and 22 of Application No. 17/389,922;
Claims 1-3, 5-12, 16, and 20-22 of Application No. 17/390,064.
This is a provisional nonstatutory double patenting rejection.
Claims 48-54, 59-63, 71, 83, and 85-93 stand as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-15, 17-18, and 20-27 of copending Application No. 17/387,205 in view of WO 2018/185526 A1 (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as “Levengood”).
Claims 48-49, 59-63, 71, and 83-93 stand as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 9, 11-13, 17-33, 36-42, 44, 46-51, 53, 55-59, and 63 of copending Application 16/488,764 in view of WO 2018/185526 A1 (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as “Levengood”).
Claims 48-49, 53-63, 71, 83-84, 88, and 93 stand as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-20, and 22 of copending Application 17/389,922 in view of WO 2018/185526 A1 (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as “Levengood”).
Claims 48-53, 59-63, 71, 83-84, 88, and 93 stand as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-12, 16, and 20-22 of copending Application 17/390,064 in view of WO 2018/185526 A1 (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as “Levengood”).
Claims 48-53, 59-63, 71, 83-84, 88, and 93 stand as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-12, 16, and 20-22 of copending Application 17/387,205 in view of WO 2018/185526 A1 (previously cited on PTO-892; herein after referred to as "Zhao") in view of non-patent literature by Levengood et. al. (Angew. Chem. Intl. Ed., 2017, 56, 733-737; previously cited on PTO-892; herein after referred to as “Levengood”).
It is noted that Applicant has not presented any arguments against the above-listed maintained claim rejections under nonstatutory double patenting. In the Response After Final Action (04/27/2026), Applicant requested that the claim rejections of record under nonstatutory double patenting be held in abeyance, and no arguments regarding the rejections were provided. Thus, as provided in the previous Office Action (Advisory Action dated 05/01/2026), the above-listed claim rejections under nonstatutory double patenting are maintained.
Conclusion
Claims 48-93 are pending. Claims 55-58, 64-70, and 72-82 are withdrawn. Claims 48-54, 59-63, 71, and 83-93 are rejected. No claims are allowed.
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.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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