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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 3, 2025 has been entered.
Claims 18, 24, 31, 34-35, 37, 42 and 43 are pending.
Claims 35, 37 and 43 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.
Claims 18, 24, 31, 34 and 42, drawn to conjugate, are being acted upon in this Office Action.
Priority
Acknowledgement is made that this application is a 371 National Stage Entry of International Application PCT/CN2021/087323 filed April 14, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 3, 2025 has been considered by the examiner and an initialed copy of the IDS is included with this Office Action.
Specification
The substitute specification filed on Oct 18, 2023 is objected to because it contains disclosures of amino acid sequences “GALPETGG” and “LPETGG” that are not accompanied by SEQ ID NOs, at least with respect to the sequences shown in page 74, lines 15 and 16. Amending the specification to include “GALPETGG (SEQ ID NO: 18) and “LPETGG (SEQ ID NO: 13)” would obviate this objection.
Claim Objection
Claim 18 is objected to under 37 C.F.R. 1.821(a) and (c) for failing to recite a sequence identifier (SEQ ID NO:). See MPEP 2422.01-03.
Rejection Withdrawn
The objection to claim 18 with respect to any integer is withdrawn in view of the claim amendment.
The enablement rejection of claims 18, 24-27, 31, 33-34 and 38-42 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in light of the claims amendment.
The provisional rejection of claims 18, 24-27, 31, 33-34 and 38-42 rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 35, 36, 37, 44, 48-49 of copending Application No. 18/620,025 is withdrawn in view of the claim amendment.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 24 and 31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
The recitation of "R11” in claims 24 and 31 is indefinite because the metes and bounds of what would constitute “R11” cannot be determined. One of ordinary skill in the art would not reasonably be apprised of the metes and bounds of the invention.
Amending the claims to recite “wherein R11 is C6-alkyl or methyl” would obviate this rejection, see p 13, para. [0051].
In the event of rejoinder, claim 37 will be rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph because the metes and bounds of claim 37 render vague and indefinite since the claim depends from canceled claim 36. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See MPEP § 2173.05(d). MPEP § 608.01(n).
Claim rejections under - 35 U.S.C. 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 18, 24, 31, 34 and 42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP § 2163 lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include: the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For claims drawn to a genus, MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus, See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406, M.P.E.P. § 2163, II, A, 3, (a), (ii).
Claim 18 encompasses any conjugate having the structure of formula (III-1):
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Wherein L1 is -Gly-Gly-Phe-Gly- (SEQ ID NO: 8),
L2 is a C2-2o alkylene wherein one or two -CH2- structures in the alkylene is optionally replaced by -(CO)-;
n is an integer of 2 to 20;
d is 0, or is an integer of 1 to 3;
each i is independently an integer of 1 to 12;
each j is independently an integer of 1 to 12;
each k is independently an integer of 1 to 12;
P is a payload which is linked to the B moiety or L' moiety, wherein the payload is selected from
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and
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A is an anti-human HER2 monoclonal antibody connected to the rest of the conjugate through a modified heavy chain and/or light chain C-terminal, wherein the modified heavy chain and/or light chain C-terminal is modified to comprise Leu-Pro-Xaa-Thr, wherein Xaa is any natural or unnatural single amino acid; z is an integer of 1 to 4.
Regarding heavy chain and/or light chain C-terminal is modified to comprise Leu-Pro-Xaa-Thr, the specification discloses LPXTG (SEQ ID NO: 11), LPETG (SEQ ID NO: 12), LPETGG (SEQ ID NO: 13), GALPXT (SEQ ID NO: 23) wherein X is any amino acid.
The specification discloses:
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SEQ ID NO:19DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGALPET
SEQ ID NO:20DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGALPET
SEQ ID NO:21EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGALPET
It should be noted that all heavy and light chain sequences above end with GALPET or GALPETGG except SEQ ID NO: 2.
However, the specification does not disclose any light chain and/or heavy chain ends with Leu-Pro-Xaa-Thr (aka LPXT) in amended claim 18. This is new matter. Applicant is required to remove this sequence in response to this Office Action. Note, amending claim 18 to recite GALPXT (SEQ ID NO: 23) in place of Leu-Pro-Xaa-Thr would obviate this issue.
Regarding any anti-human HER2 monoclonal antibody, the specification as filed discloses just one anti-human HER2 monoclonal antibody, namely trastuzumab. This one species fails to convey evidence of possession of the entire genus. In particular, the specification does NOT describe the structure-identifying information, e.g., amino acid sequence about the heavy and light chain variable regions of genus of anti-human HER2 monoclonal antibodies that correlated with binding to human HER2 encompassed by the claimed conjugate. The specification does not describe a representative number of species falling with the scope of the genus or structural common to the members of the genus of anti-human HER2 monoclonal antibodies so the one of skill in the art can visualize or recognize the member of the genus of the actual claimed conjugate comprising said anti-human HER2 monoclonal antibody themselves.
It is known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope.
For example, Lloyd et al. taught that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. of record, Protein Engineering, Design & Selection 22:159-168, 2009; PTO 1449; see, e.g., Discussion).
Similarly, Edwards et al., (of record, J Mol Biol. 334(1): 103-118, Nov 14, 2003; PTO 1449), found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein; 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (Abstract).
In this case, “knowledge of the chemical structure of an antigen, e.g., human HER2, [does not give] the required kind of structure-identifying information about the corresponding antibodies”), See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)
Given that hundreds of unique antibody structures may bind a single antigen, the structure of an antibody cannot be predicted from the structure of the antigen (as held in Amgen), and a single species, or small group of species, cannot define a structure-function relationship so as to be representative of all the antibodies that bind to that antigen (as held in Abbvie).
Further, even a minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may affect IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics.
For example, Piche-Nicholas et al (of record, MABS 10(1): 81-94, 2018; PTO 1449) teaches altering complementary-determining region (CDRs) by 1-5 mutations significantly alter binding affinity to FcRn in vitro, see entire document, abstract, p. 95, right col, in particular. Engineering CDRs by modify local charge and thus maintain affinity to FcRn at 400 nM or weaker in vitro while retaining antigen binding may have far-reaching implications in the half-life optimization efforts of IgG therapeutics with respect to in vivo pharmacokinetics, see p. 90, in particular.
When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A description of what a material does, rather than of what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In Abbvie v. Centocor (Fed. Cir. 2014), the Court held that a disclosure of many different antibodies (in that case neutralizing antibodies to IL-12 with a particular binding affinity) was not enough to support the genus of all IL-12 neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004)
Regarding claim 24, the claim recites the structures:
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However, the variable R11 is not defined in the claim.
Regarding claim 31, the claim recites the structures:
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However, the variable R11 is not defined in the claim.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Therefore, only a conjugate having any one of the structure as set forth in claim 31 wherein the antibody A is an anti-human HER2 antibody wherein the anti-human HER2 antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 19 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 21, wherein z is 1 to 4, wherein each I, i1, i2, i3, i4 is independently an integer of 1 to 12, wherein each j is independently an integer of 1 to 12, but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Applicants’ arguments filed April 30, 2025 have been fully considered but are not found persuasive.
Applicants’ position is that Claim 18 is amended to (i) replace "any integer" with "an integer" and (ii) delete "-Gly- Phe-Leu-Gly-". Claim 18 is amended to (i) specify that A is an anti-human monoclonal HER2 antibody connected to the rest of the conjugate through a modified heavy chain and/or light chain C-terminal, wherein the modified heavy chain and/or light chain C-terminal is modified to comprise Leu-Pro-Xaa-Thr, wherein Xaa is any natural or unnatural single amino acid, (ii) limit L1 to GGFG, (iii) limit the payload to DX8951f and Dxd- (1), (iv) replace "any integer" with "an integer", (v) delete "unnatural" before "single amino acid", and (vi) limit Z to 1-4, d to 0-3, and i, j, k to 1-12. Claim 24 is amended to limit i, ii, i2, i3, i4, and j to 1 to 12. Claim 35 is amended to specify that the disease is a HER2-positive tumor. Claims 34 and 35 are amended to delete "prophylactically". Claims 25, 26, 27, 33, 36, and 38-41 are cancelled. Support for the amendments may be found throughout the specification, e.g., at paragraphs [018], [042], [053], [059], [075]-[077], [127], [138], [158], [159], and [160] and in the originally filed claims.
Claim 18 is amended to delete "unnatural" from the phrase " Leu-Pro-Xaa-Thr, wherein Xaa is any natural or unnatural single amino acid". As disclosed in paragraph [059], the ligase recognition sequence of Sortase is LPXTG. It is well established in the art that the position X within this motif is variable. Information which is well known in the art need not be described in detail in the specification. See M.P.E.P. § 2163. Based on the knowledge in the art and the specification, a person of ordinary skill in the art would reasonably understand that any natural amino acid can occupy the X position in the LPXTG motif.
Applicant submits that these amendments render the objection moot and respectfully request withdrawal of the objection.
In response, the amendment to claims 18, 24, 42 and 43 is acknowledged.
Regarding claim 18, the specification discloses just trastuzumab. It should be noted that all heavy and light chain sequences above end with GALPET or GALPETGG except SEQ ID NO: 2, not LPXT.
However, the specification does not disclose any light chain and/or heavy chain ends with Leu-Pro-Xaa-Thr (aka LPXT). This is new matter. Applicant is required to remove this sequence in response to this Office Action. Note, amending claim 18 to recite GALPXT (SEQ ID NO: 23) in place of Leu-Pro-Xaa-Thr would obviate this issue.
Regarding any anti-human HER2 monoclonal antibody, the specification as filed discloses just one anti-human HER2 monoclonal antibody, namely trastuzumab. One species fails to convey evidence of possession of the entire genus. In particular, the specification does not describe the structure-identifying information, e.g., amino acid sequence about the heavy and light chain variable regions of genus of anti-human HER2 monoclonal antibodies that correlated with binding to human HER2 encompassed by the claimed conjugate. The specification does not describe a representative number of species falling with the scope of the genus or structural common to the members of the genus of anti-human HER2 monoclonal antibodies so the one of skill in the art can visualize or recognize the member of the genus of the actual claimed conjugate comprising said anti-human HER2 monoclonal antibody themselves.
It is known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope.
For example, Lloyd et al. taught that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. of record, Protein Engineering, Design & Selection 22:159-168, 2009; PTO 1449; see, e.g., Discussion).
Similarly, Edwards et al., (of record, J Mol Biol. 334(1): 103-118, Nov 14, 2003; PTO 1449), found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein; 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (Abstract).
In this case, “knowledge of the chemical structure of an antigen, e.g., human HER2, [does not give] the required kind of structure-identifying information about the corresponding antibodies”), See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)
Given that hundreds of unique antibody structures may bind a single antigen, the structure of an antibody cannot be predicted from the structure of the antigen (as held in Amgen), and a single species, or small group of species, cannot define a structure-function relationship so as to be representative of all the antibodies that bind to that antigen (as held in Abbvie).
Further, even a minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may affect IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics.
For example, Piche-Nicholas et al (of record, MABS 10(1): 81-94, 2018; PTO 1449) teaches altering complementary-determining region (CDRs) by 1-5 mutations significantly alter binding affinity to FcRn in vitro, see entire document, abstract, p. 95, right col, in particular. Engineering CDRs by modify local charge and thus maintain affinity to FcRn at 400 nM or weaker in vitro while retaining antigen binding may have far-reaching implications in the half-life optimization efforts of IgG therapeutics with respect to in vivo pharmacokinetics, see p. 90, in particular.
When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A description of what a material does, rather than of what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In Abbvie v. Centocor (Fed. Cir. 2014), the Court held that a disclosure of many different antibodies (in that case neutralizing antibodies to IL-12 with a particular binding affinity) was not enough to support the genus of all IL-12 neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004)
Regarding claim 24, the claim recites the structures:
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However, the variable R11 is not defined in the claim.
Regarding claim 31, the claim recites the structures:
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However, the variable R11 is not defined in the claim.
For these reasons, the rejection is maintained.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Clams 18, 24, 31, 34 and 42 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 9-14 and 16 of copending Application No. 18/994,258. Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims differ only in scope.
Copending claim 9 recites a conjugate having the structure of formula (III):
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, which corresponds to instant claim 18 wherein the drug limits to Dxd-(1), Dxd-(2) and DX8951f (species).
Copending claim 10 recites the conjugate of claim 9, wherein
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, which corresponds to instant claim 23.
Copending claim 11 recites the conjugate of claim 9, wherein
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,
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, which corresponds to instant claim 24 (conjugate LC302-1).
Copending claim 12 recites the conjugate of claim 9, wherein the conjugate of claim 9,wherein the targeting molecule is an antibody or an antigen binding fragment thereof; the antibody or antigen binding fragment is preferably modified to connect with the G. moiety in the compound of formula (I);preferably, A is an anti-human monoclonal antibody connected to the rest of the conjugate through a modified heavy chain and/or light chain C-terminal, wherein the modified heavy chain and/or light chain C-terminal is modified to comprise Leu-Pro-Xaa-Thr, wherein Xaa is any natural or unnatural single amino acid, and z is 2;preferably, the antibody is an anti-human HER2 antibody, an anti-human TROP2 antibody or anti-FGFR3 antibody, which corresponds to instant claims 26, 27.
Copending claim 13 recites the conjugate of claim 9, wherein the payload is a cytotoxin or a fragment thereof, with an optional derivatization in order to connect to the B moiety or L moiety in the compound of formula (I); preferably, the cytotoxin is selected from the group consisting of taxanes, maytansinoids, auristatins, epothilones, combretastatin A-4 phosphate, combretastatin A-4 and derivatives thereof, indol-sulfonamides, vinblastines such as vinblastine, vincristine, vindesine, vinorelbine, vinflunine, vinglycinate, anhy-drovinblastine, dolastatin 10 and analogues, halichondrin B, eribulin, indole-3-oxoacetamide, podophyllotoxins, 7-diethylamino-3-(2'-benzoxazolyl)- coumarin (DBC), discodermolide, laulimalide, camptothecins and derivatives thereof, mitoxantrone, mitoguazone, nitrogen mustards, nitrosoureasm, aziridines, benzodopa, carboquone, meturedepa, uredepa, dynemicin, esperamicin, neocarzinostatin, aclacinomycin, actinomycin, antramycin, bleomycins, actinomycin C, carabicin, carminomycin, cardinophyllin, carminomycin, actinomycin D, daunorubicin, detorubicin, adriamycin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins, nogalamycin, olivomycin, peplomycin, porfiromycin, puromycin, ferric adriamycin, rodorubicin, rufocromomycin, streptozocin, zinostatin, zorubicin, trichothecene, T-2 toxin, verracurin A, bacillocporin A, anguidine, ubenimex, azaserine, 6-diazo-5-oxo-L- norleucine, dimethyl folic acid, methotrexate, pteropterin, trimetrexate, edatrexate, fludarabine, 6- mercaptopurine, tiamiprine, thioguanine, ancitabine, gemcitabine, enocitabine, azacitidine, 6- azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, floxuridine, calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone, aminoglutethimide, mitotane, trilostane, flutamide, nilutamide, bicalutamide, leuprorelin acetate, protein kinase inhibitors and a proteasome inhibitors; and/or selected from vinblastines, colchicines, taxanes, auristatins, maytansinoids, calicheamicin, doxonubicin, duocarmucin, SN-38, cryptophycin analogue, deruxtecan, duocarmazine, calicheamicin, centanamycin, dolastansine, pyrrolobenzodiazepine, exatecan and derivatives thereof; and/or selected from auristatins, especially MMAE, MMAF or MMAD; and/or selected from exatecan and derivatives thereof, such as DX8951f; GQH-23-US selected from DXd-(1) and DXd-(2); preferably DXd-(1) whereas instant claim 18 limits the payload or drug to DX8951F, Dxd-(1), Dxd-(2), which corresponds to instant claim 18.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Applicants’ arguments filed April 30, 2025 have been fully considered but are not found persuasive.
Applicant’s position that [T]he present application has the earlier patent term filing date than copending Applications No. 18/994,258 and 18/620,025.
MPEP 804 states that:
If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.
In response, the claims are not ready for allowance and provisional nonstatutory double patenting rejection is NOT the only rejection remaining in an application. Therefore, the rejection is maintained.
Conclusion
No claim is allowed.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641