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 .
Claims 25-33, 35 and 75-77 are pending and being acted upon in this Office Action.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d).
Specification
The amendment to the specification has been entered.
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 25-33, 35 and 75-77 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. This is a written description rejection.
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: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. “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.”
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Additionally, “An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.” Amgen Inc v. Sanofi 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). “Further, the “newly characterized antigen” test flouts basic legal principles of the written description requirement. Section 112 requires a “written description of the invention.” But this test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law's other requirements are met, one obtains a patent.” Ariad, 598 F.3d at 1345.” Amgen at 1362.
The claims encompass any antibody drug conjugates (ADC) comprising KSP inhibitors having the structures attached to any antibody or antigen-binding fragment thereof (claims 25-33, 35) wherein the antibody or antigen-binding fragment thereof that bind to any extracellular target molecule (claim 75), any extracellular cancer target molecule (claim 76) wherein after binding to the undisclosed extracellular target molecule on the target cell is internalized by the target cell through binding (claim 77) for the treatment hyperproliferative disease, angiogenesis, cancers and tumors.
Regarding antibody or antigen binding fragment thereof, the specification discloses:
TPP-8382 (anti B7H3), TPP-6013 (anti-CD123), TPP-8987 (anti-CD123), TPP-8988 (anti-CD123), TPP 9476 (anti-CD123), TPP-9574 (anti-CXCR5) and TPP 9580 (anti-CXCR5). Here, preference is given to the antibodies (AK) TPP-6013, TPP-8987, TPP-8988 and TPP-9476 (in each case anti-CD123).
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However, the specification does not describe the structure-identifying information i. Complete structure, i.e., amino acid sequence of heavy and light chain variable domains, or ii. Partial structure, i.e., the six CDRs, iii. Physical and/or chemical properties and iv Functional characteristics, i.e., binding affinity or epitope specificity share by members of the genus of antibody or antigen binding fragment thereof that binds to any extracellular target molecule, any extracellular cancer target molecule or any extracellular target molecule that internalized after binding encompassed by the claimed antibody-drug conjugates, nor describe a representative number of species of antibodies falling within the scope of the genus or structural feature common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of the actual claimed antibody-drug conjugate themselves as a pharmaceutical composition for treating any and all cancer.
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 892; see, e.g., Discussion).
Similarly, Edwards et al., (of record, J Mol Biol. 334(1): 103-118, 2003; PTO 892), 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).
Poosarla et al (of record, Biotechn. Bioeng., 2017, 114(6): 1331-1342, 2017; PTO 892) teach substantial diversity in designed mAbs (sharing less than 75% sequence similarity to all existing natural antibody sequences) that bind to the same 12-mer peptide, binding to different epitopes on the same peptide. Said reference further teaches “most B-cell epitopes... in nature consist of residues from different regions of the sequence and are discontinuous...de novo antibody designs against discontinuous epitopes present additional challenges...". (See entire reference.)
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).
Regarding n is 1 to 50 (claims 25-30, 35, 75-77) or n is 1 to 20 (claim 31), the specification discloses the drug to antibody ratio is about 3 to about 6, see p. 129, 129, and 137.
However, neither the specification nor the art teach a double digit number of drugs per antibody, such as 50 or 20 drugs per antibody without severe systemic toxicity, e.g., neutropenia and mucositis. Further, it is not clear the antibody-drug conjugate is cell-permeable, to be accumulate inside the tumor cells. There are no in vivo working examples.
Nejadmoghaddam (of record, Avicenna Journal of Medical Biotechnology 2(1): 3-23, 2019; PTO 892) discusses major obstacles of antibody-drug conjugates include off-target toxicity, tumor marker selection, antibody specificity, adequately affinity and receptor-mediated internalization are major aspects of choice, cytotoxic payload (e.g., up to 7 drugs per antibody), cytotoxic payload linkage strategy, aqueous solubility, non-immunogenic and stability in storage and bloodstream, see entire document, abstract, p. 15, in particular.
Regarding pharmaceutical acceptable salt thereof (claims 25-33, 35, 75-77), the specification has not provided a written description of the reagents or conditions for the formation of a single salt for any antibody drug conjugates encompassed by the claims. For example, It would not be expected that the reagents or conditions disclosed for the formation of crystalized unconjugated cetuximab or Mab h425 would be the same reagents or conditions for the formation of salts, hydrates or solvates for the instant genus of anti-Her3 conjugates claimed because Matheus et al teach that the crystallization of cetuximab and Mab h425 was an unexpected result.
Matheus et al (of record, US 7,960,516) teach that antibodies exhibit a tendency towards aggregation which causes difficulties in crystallization (column 2, lines 58-61) and a tendency towards denaturation during the crystallization process (column 2, lines 63-66).
Morissette et al (of record, Advanced Drug Delivery Reviews, Vol. 56, pp. 275-300, 2004; PTO 892) teach high through put method to determine optimal crystallization techniques for the formation of salts and solvates (title). Morissette et al do not specifically address high through put methods to determine optimal crystallization techniques for the formation of salts and solvates of antibodies that circumvent aggregation and denaturation. Further, the ability to screen for the required salt of a particular antibody which is not the inventive antibodies does not provide an adequate written description of the salt comprising the antibody conjugate in a non-aggregated, non-denatured state because one of skill in the art cannot describe what is yet to be made. For these reasons, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
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. Thus, the specification fails to describe these DNA sequences.
For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
Therefore, only (1) an antibody-drug conjugate of formula I wherein the antibody is any antibody disclosed in Table 1 and wherein n is 1 to 8, or 4 to 8, 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 23, 2026 have been fully considered but are not found persuasive.
Applicant respectfully submits the claims, including the amendments made, are expressly and explicitly disclosed in the Specification as filed, see e.g. the original claims 1-24, or at pp. 5-7, 13, 21 and 29 in the original PCT application, PCT/EP2017/082789.
Accordingly, the pending claims 25-35 and 75-77 comply with the written description requirements. Reconsideration and withdrawal of the rejections are therefore respectfully requested.
In response, the claims encompass any antibody drug conjugates (ADC) comprising KSP inhibitors having the structures attached to any antibody or antigen-binding fragment thereof (claims 25-33, 35) wherein the antibody or antigen-binding fragment thereof that bind to any extracellular target molecule (claim 75), any extracellular cancer target molecule (claim 76) wherein after binding to the undisclosed extracellular target molecule on the target cell is internalized by the target cell through binding (claim 77) for the treatment hyperproliferative disease, angiogenesis, cancers and tumors.
The claims encompass any antibody drug conjugates (ADC) comprising KSP inhibitors having the structures attached to any antibody or antigen-binding fragment thereof (claims 25-33, 35) wherein the antibody or antigen-binding fragment thereof that bind to any extracellular target molecule (claim 75), any extracellular cancer target molecule (claim 76) wherein after binding to the undisclosed extracellular target molecule on the target cell is internalized by the target cell through binding (claim 77) for the treatment hyperproliferative disease, angiogenesis, cancers and tumors.
Regarding antibody or antigen binding fragment thereof, the specification discloses:
TPP-8382 (anti B7H3), TPP-6013 (anti-CD123), TPP-8987 (anti-CD123), TPP-8988 (anti-CD123), TPP 9476 (anti-CD123), TPP-9574 (anti-CXCR5) and TPP 9580 (anti-CXCR5). Here, preference is given to the antibodies (AK) TPP-6013, TPP-8987, TPP-8988 and TPP-9476 (in each case anti-CD123).
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However, the specification does not describe the structure-identifying information i. Complete structure, i.e., amino acid sequence of heavy and light chain variable domains, or ii. Partial structure, i.e., the six CDRs, iii. Physical and/or chemical properties and iv Functional characteristics, i.e., binding affinity or epitope specificity share by members of the genus of antibody or antigen binding fragment thereof that binds to any extracellular target molecule, any extracellular cancer target molecule or any extracellular target molecule that internalized after binding encompassed by the claimed antibody-drug conjugates, nor describe a representative number of species of antibodies falling within the scope of the genus or structural feature common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of the actual claimed antibody-drug conjugate themselves as a pharmaceutical composition for treating any and all cancer.
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 892; see, e.g., Discussion).
Similarly, Edwards et al., (of record, J Mol Biol. 334(1): 103-118, 2003; PTO 892), 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).
Poosarla et al (of record, Biotechn. Bioeng., 2017, 114(6): 1331-1342, 2017; PTO 892) teach substantial diversity in designed mAbs (sharing less than 75% sequence similarity to all existing natural antibody sequences) that bind to the same 12-mer peptide, binding to different epitopes on the same peptide. Said reference further teaches “most B-cell epitopes... in nature consist of residues from different regions of the sequence and are discontinuous...de novo antibody designs against discontinuous epitopes present additional challenges...". (See entire reference.)
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).
Regarding n is 1 to 50 (claims 25-30, 35, 75-77) or n is 1 to 20 (claim 31), the specification discloses the drug to antibody ratio is about 3 to about 6, see p. 129, 129, and 137.
However, neither the specification nor the art teach a double digit number of drugs per antibody, such as 50 or 20 drugs per antibody without severe systemic toxicity, e.g., neutropenia and mucositis. Further, it is not clear the antibody-drug conjugate is cell-permeable, to be accumulate inside the tumor cells. There are no in vivo working examples.
Nejadmoghaddam (of record, Avicenna Journal of Medical Biotechnology 2(1): 3-23, 2019; PTO 892) discusses major obstacles of antibody-drug conjugates include off-target toxicity, tumor marker selection, antibody specificity, adequately affinity and receptor-mediated internalization are major aspects of choice, cytotoxic payload (e.g., up to 7 drugs per antibody), cytotoxic payload linkage strategy, aqueous solubility, non-immunogenic and stability in storage and bloodstream, see entire document, abstract, p. 15, in particular.
Regarding pharmaceutical acceptable salt thereof (claims 25-33, 35, 75-77), the specification has not provided a written description of the reagents or conditions for the formation of a single salt for any antibody drug conjugates encompassed by the claims. For example, It would not be expected that the reagents or conditions disclosed for the formation of crystalized unconjugated cetuximab or Mab h425 would be the same reagents or conditions for the formation of salts, hydrates or solvates for the instant genus of anti-Her3 conjugates claimed because Matheus et al teach that the crystallization of cetuximab and Mab h425 was an unexpected result.
Matheus et al (of record, US 7,960,516) teach that antibodies exhibit a tendency towards aggregation which causes difficulties in crystallization (column 2, lines 58-61) and a tendency towards denaturation during the crystallization process (column 2, lines 63-66).
Morissette et al (of record, Advanced Drug Delivery Reviews, Vol. 56, pp. 275-300, 2004; PTO 892) teach high through put method to determine optimal crystallization techniques for the formation of salts and solvates (title). Morissette et al do not specifically address high through put methods to determine optimal crystallization techniques for the formation of salts and solvates of antibodies that circumvent aggregation and denaturation. Further, the ability to screen for the required salt of a particular antibody which is not the inventive antibodies does not provide an adequate written description of the salt comprising the antibody conjugate in a non-aggregated, non-denatured state because one of skill in the art cannot describe what is yet to be made. For these reasons, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
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 of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant is reminded that in order to demonstrate that Applicant has invented what is claimed, the specification must adequately describe representative species of antibodies that reflect the structural diversity of the claimed genus (see Eli Lilly, 119 F.3d at 1568 (“[N]aming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of the material.”); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) (“Claiming all DNA that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived”).
For these reasons, the rejection is maintained.
Claims 25-33, 35 and 75-77 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an antibody-drug conjugate of formula I wherein the antibody is any antibody disclosed in Table 1 and wherein n is 1 to 8, or 4 to 8, does not reasonably provide enablement for any antibody-drug conjugate as set forth in claims 25-33, 35 and 75-77. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. . In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The claims encompass any antibody drug conjugates (ADC) comprising KSP inhibitors having the structures attached to any antibody or antigen-binding fragment thereof (claims 25-33, 35) wherein the antibody or antigen-binding fragment thereof that bind to any extracellular target molecule (claim 75), any extracellular cancer target molecule (claim 76) wherein after binding to the undisclosed extracellular target molecule on the target cell is internalized by the target cell through binding (claim 77) for the treatment hyperproliferative disease, angiogenesis, cancers and tumors.
Enablement is not commensurate in scope with the claims for the following reasons:
Regarding antibody or antigen binding fragment thereof, the specification discloses:
TPP-8382 (anti B7H3), TPP-6013 (anti-CD123), TPP-8987 (anti-CD123), TPP-8988 (anti-CD123), TPP 9476 (anti-CD123), TPP-9574 (anti-CXCR5) and TPP 9580 (anti-CXCR5). Here, preference is given to the antibodies (AK) TPP-6013, TPP-8987, TPP-8988 and TPP-9476 (in each case anti-CD123).
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However, the specification does not teach i. Complete structure, i.e., amino acid sequence of heavy and light chain variable domains, or ii. Partial structure, i.e., the six CDRs, iii. Physical and/or chemical properties and iv Functional characteristics, i.e., binding affinity or epitope specificity share by members of the genus of antibody or antigen binding fragment thereof that binds to any CXCR5 or common structure share by members of the genus of antibodies to enable one of skill in the art to make and use the claimed antibody-drug conjugates.
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 892; see, e.g., Discussion).
Similarly, Edwards et al., (of record, J Mol Biol. 334(1): 103-118, 2003; PTO 892), 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).
Poosarla et al (of record, Biotechn. Bioeng., 2017, 114(6): 1331-1342, 2017; PTO 892) teach substantial diversity in designed mAbs (sharing less than 75% sequence similarity to all existing natural antibody sequences) that bind to the same 12-mer peptide, binding to different epitopes on the same peptide. Said reference further teaches “most B-cell epitopes... in nature consist of residues from different regions of the sequence and are discontinuous...de novo antibody designs against discontinuous epitopes present additional challenges...". (See entire reference.)
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, 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.
Regarding n is 1 to 50 (claims 25-30, 35, 75-77) or n is 1 to 20 (claim 31), the specification discloses the drug to antibody ratio is about 3 to about 6, see p. 129, 129, and 137.
However, neither the specification nor the art teach a double digit number of drugs per antibody, such as 50 or 20 drugs per antibody without severe systemic toxicity, e.g., neutropenia and mucositis. Further, it is not clear the conjugate is cell-permeable, to be accumulate inside the tumor cells. There are no in vivo working examples.
Nejadmoghaddam (of record, Avicenna Journal of Medical Biotechnology 2(1): 3-23, 2019; PTO 892) discusses major obstacles of antibody-drug conjugates include off-target toxicity, tumor marker selection, antibody specificity, adequately affinity and receptor-mediated internalization are major aspects of choice, cytotoxic payload (e.g., up to 7 drugs per antibody), cytotoxic payload linkage strategy, aqueous solubility, non-immunogenic and stability in storage and bloodstream, see entire document, abstract, p. 15, in particular.
There are no in vivo working examples. It is unpredictable which antibody-drug conjugate having 50 drugs per antibody is effective for treating which disease associated with CXCR5 expression.
Regarding pharmaceutical acceptable salt thereof (claims 25-33, 35, 75-77), the specification fails to provide any teachings for how to make the solid forms of salts of the instant antibody conjugates encompassed by the claims. For example, It would not be expected that the reagents or conditions disclosed for the formation of crystalized unconjugated cetuximab or Mab h425 would be the same reagents or conditions for the formation of salts, hydrates or solvates for the instant genus of anti-Her3 conjugates claimed because Matheus et al teach that the crystallization of cetuximab and Mab h425 was an unexpected result.
Matheus et al (of record, US 7,960,516) teach the unexpected result that stable pharmaceuticals can be prepared with solid forms of cetuximab and Mab h425 (column 4, lines 56-59) and that the antibodies are biologically active after re-dissolution (column 10, lines 51-59). Matheus et al teach that the crystallization of intact glycosylated antibodies is extremely difficult due to the size of the protein, the different glycosylation patterns of the individual molecules and associated micro-heterogeneities as well as the structural flexibility of the immunoglobulin make an ordered incorporation into a crystal lattice more difficult or even impossible (column 2, lines 50-56) and that there is a risk of denaturing antibodies during the crystallization process (column 2, lines 63-66). It is noted that the number of drugs attached to a single antibody varies between 1-50 (subscript “n”) in claims 25-30, 35, 75-77 or n is 20 in claim 31. The cumulative number of drug moieties plus linker required in the antibody-conjugate would vastly increase the size of the molecule, and alter flexibility and the micro-heterogeneity, especially since the number of attachments to a single antibody vary from 1-50. These factors are in opposition to the formation of an ordered crystal lattice necessary for solid phase salt formation. Antibodies have aqueous solubility of over 200 mg/ml in histidine buffer at pH 6 (Ke et al, International Journal of Pharmaceutics, Vol. 548, pp. 682-688, 2015, PTO 892, see page 684, first column, lines 6-7, page 683, lines 3-4 under section 2.2.2, lines 2-3 under section 2.2.3). The influence of a group that is much less hydrophilic than the antibody, such as the instant kinesin spindle inhibitor derivatives, on the ability of the antibody to go into a crystal lattice of a salt is unknown. Thus one of skill in the art would be subject to undue experimentation in order to make the salts of any antibody-drug conjugates.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19 24 (CCPA 1970).
In re wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988), the decision of the court indicates that the more unpredictable the area is, the more specific enablement is necessary.
Applicants’ arguments filed April 23, 2026 have been fully considered but are not found persuasive.
Applicant respectfully submits the instant claims are drawn to conjugates comprising three structure-specific components: a Markush moiety rich in amino-acid like functional groups, a linker M with a specific carbonyl- containing chain, and an antibody or fragment AK specifically linked to M through either a sulfur atom of a cysteine side chain or nitrogen atom of a lysine side-chain regardless of its sequences. The original disclosure contains sufficient information regarding the claimed conjugates. For example, the Specification provides Examples at pp. 75-111, illustrating general synthesis schemes, and specific synthesis of the intermediates and the specific species within the Markush moiety. Then, the Specification provides Examples at pp. 113-161, illustrating the specific synthesis of different conjugates and their biological activities. These close to 100 pages of disclosure directs and enables one in the art to first make and then use the claimed invention.
Accordingly, claims 25-35 and 75-77 comply with the enablement requirements. Reconsideration and withdrawal of the rejections are therefore respectfully requested.
In response, the claims encompass any antibody drug conjugates (ADC) comprising KSP inhibitors having the structures attached to any antibody or antigen-binding fragment thereof (claims 25-33, 35) wherein the antibody or antigen-binding fragment thereof that bind to any extracellular target molecule (claim 75), any extracellular cancer target molecule (claim 76) wherein after binding to the undisclosed extracellular target molecule on the target cell is internalized by the target cell through binding (claim 77) for the treatment hyperproliferative disease, angiogenesis, cancers and tumors.
Enablement is not commensurate in scope with the claims for the following reasons:
Regarding antibody or antigen binding fragment thereof, the specification discloses:
TPP-8382 (anti B7H3), TPP-6013 (anti-CD123), TPP-8987 (anti-CD123), TPP-8988 (anti-CD123), TPP 9476 (anti-CD123), TPP-9574 (anti-CXCR5) and TPP 9580 (anti-CXCR5). Here, preference is given to the antibodies (AK) TPP-6013, TPP-8987, TPP-8988 and TPP-9476 (in each case anti-CD123).
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However, the specification does not teach i. Complete structure, i.e., amino acid sequence of heavy and light chain variable domains, or ii. Partial structure, i.e., the six CDRs, iii. Physical and/or chemical properties and iv Functional characteristics, i.e., binding affinity or epitope specificity share by members of the genus of antibody or antigen binding fragment thereof that binds to any antigen, any extracellular target molecule, any extracellular cancer target molecule or common structure share by members of the genus of antibodies to enable one of skill in the art to make and use the claimed antibody-drug conjugates.
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 892; see, e.g., Discussion).
Similarly, Edwards et al., (of record, J Mol Biol. 334(1): 103-118, 2003; PTO 892), 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).
Poosarla et al (of record, Biotechn. Bioeng., 2017, 114(6): 1331-1342, 2017; PTO 892) teach substantial diversity in designed mAbs (sharing less than 75% sequence similarity to all existing natural antibody sequences) that bind to the same 12-mer peptide, binding to different epitopes on the same peptide. Said reference further teaches “most B-cell epitopes... in nature consist of residues from different regions of the sequence and are discontinuous...de novo antibody designs against discontinuous epitopes present additional challenges...". (See entire reference.)
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, 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.
Regarding n is 1 to 50 (claims 25-30, 35, 75-77) or n is 1 to 20 (claim 31), the specification discloses the drug to antibody ratio is about 3 to about 6, see p. 129, 129, and 137.
However, neither the specification nor the art teach a double digit number of drugs per antibody, such as 50 or 20 drugs per antibody without severe systemic toxicity, e.g., neutropenia and mucositis. Further, it is not clear the conjugate is cell-permeable, to be accumulate inside the tumor cells.
Nejadmoghaddam (of record, Avicenna Journal of Medical Biotechnology 2(1): 3-23, 2019; PTO 892) discusses major obstacles of antibody-drug conjugates include off-target toxicity, tumor marker selection, antibody specificity, adequately affinity and receptor-mediated internalization are major aspects of choice, cytotoxic payload (e.g., up to 7 drugs per antibody), cytotoxic payload linkage strategy, aqueous solubility, non-immunogenic and stability in storage and bloodstream, see entire document, abstract, p. 15, in particular.
There are no in vivo working examples. It is unpredictable which antibody-drug conjugate having 50 drugs per antibody is effective for treating any and all cancers.
Regarding pharmaceutical acceptable salt thereof (claims 25-33, 35, 75-77), the specification fails to provide any teachings for how to make the solid forms of salts of the instant antibody conjugates encompassed by the claims. For example, It would not be expected that the reagents or conditions disclosed for the formation of crystalized unconjugated cetuximab or Mab h425 would be the same reagents or conditions for the formation of salts, hydrates or solvates for the instant genus of anti-Her3 conjugates claimed because Matheus et al teach that the crystallization of cetuximab and Mab h425 was an unexpected result.
Matheus et al (of record, US 7,960,516) teach the unexpected result that stable pharmaceuticals can be prepared with solid forms of cetuximab and Mab h425 (column 4, lines 56-59) and that the antibodies are biologically active after re-dissolution (column 10, lines 51-59). Matheus et al teach that the crystallization of intact glycosylated antibodies is extremely difficult due to the size of the protein, the different glycosylation patterns of the individual molecules and associated micro-heterogeneities as well as the structural flexibility of the immunoglobulin make an ordered incorporation into a crystal lattice more difficult or even impossible (column 2, lines 50-56) and that there is a risk of denaturing antibodies during the crystallization process (column 2, lines 63-66). It is noted that the number of drugs attached to a single antibody varies between 1-50 (subscript “n”) in claims 25-30, 35, 75-77 or n is 20 in claim 31. The cumulative number of drug moieties plus linker required in the antibody-conjugate would vastly increase the size of the molecule, and alter flexibility and the micro-heterogeneity, especially since the number of attachments to a single antibody vary from 1-50. These factors are in opposition to the formation of an ordered crystal lattice necessary for solid phase salt formation. Antibodies have aqueous solubility of over 200 mg/ml in histidine buffer at pH 6 (Ke et al, International Journal of Pharmaceutics, Vol. 548, pp. 682-688, 2015, PTO 892, see page 684, first column, lines 6-7, page 683, lines 3-4 under section 2.2.2, lines 2-3 under section 2.2.3). The influence of a group that is much less hydrophilic than the antibody, such as the instant kinesin spindle inhibitor derivatives, on the ability of the antibody to go into a crystal lattice of a salt is unknown. Thus one of skill in the art would be subject to undue experimentation in order to make the salts of any antibody-drug conjugates.
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.
Claims 25-33, 35 and 75-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of U.S. Patent No. 11,660,351. Although the claims at issue are not identical, they are not patentably distinct from each other because while the ‘351 patent issued from the application which served as the parent for the present case, the examined application was filed as a CON, not a DIV, and therefore no shield against double patenting that might be provided by 35 U.S.C 121 would be applicable here.
The ’351 patent teaches the claimed antibody-drug conjugate of formula (I) comprising the same kinesin spindle protein (KSP) inhibitors conjugated to an anti-CXCR5 antibody selected from the group consisting of TPP-9574 and TPP-9580.
18182,093
11,660,351
SEQ ID NO: 92
TSGMH
TSGMH
SEQ ID NO: 93
YISSSSGFVYADAVKG
YISSSSGFVYADAVKG
SEQ ID NO: 94
SEAAF
SEAAF
SEQ ID NO: 96
RSQKSRLSRMGITPLN
RSQKSRLSRMGITPLN
SEQ ID NO: 97
RMSNLAS
RMSNLAS
SEQ ID NO: 98
AQFLEYPPT
AQFLEYPPT
Heavy chain variable domain
SEQ ID NO: 91
SEQ ID NO: 91
Light chain variable domain
SEQ ID NO: 95
SEQ ID NO: 95
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A person of skill in the art, reading the claims of the ‘351 patent, would look to the patent and follow the ‘351 patent’s express instruction on how to make the product within the patent, e.g., Examples 1-11, thereby arriving at the antibody drug conjugate of the examined claims.
Applicants’ arguments filed April 23, 2026 have been fully considered but are not found persuasive.
Applicant requests to hold the rejection in abeyance until allowable subject matter is indicated.
As such, the rejection is maintained.
Claims 25-33, 35 and 75-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-16, 18-19 of US Patent 11,478,554. Although the claims at issue are not identical, the pending claims are not patently distinct from the ‘544 claims.
Issued claim 15 recites a conjugate comprising the antibody or antigen-binding antibody fragment that binds to CXCR5, comprising a variable heavy chain comprising the variable CDR1 sequence of the heavy chain as shown in SEQ ID NO: 92, the variable CDR2 sequence of the heavy chain as shown in SEQ ID NO: 93, and the variable CDR3 sequence of the heavy chain as shown in SEQ ID NO: 94; and a variable light chain comprising the variable CDR1 sequence of the light chain as shown in SEQ ID NO: 96, the variable CDR2 sequence of the light chain as shown in SEQ ID NO: 97, and the variable CDR3 sequence of the light chain as shown in SEQ ID NO: 98, and a chemotherapeutic (generic), whereas instant claims limited the drug to kinesin spindle protein inhibitor (species).
18182,093
11,478,554
SEQ ID NO: 92
TSGMH
TSGMH
SEQ ID NO: 93
YISSSSGFVYADAVKG
YISSSSGFVYADAVKG
SEQ ID NO: 94
SEAAF
SEAAF
SEQ ID NO: 96
RSQKSRLSRMGITPLN
RSQKSRLSRMGITPLN
SEQ ID NO: 97
RMSNLAS
RMSNLAS
SEQ ID NO: 98
AQFLEYPPT
AQFLEYPPT
Heavy chain variable domain
SEQ ID NO: 91
SEQ ID NO: 91
Light chain variable domain
SEQ ID NO: 95
SEQ ID NO: 95
Issued claim 16 recites conjugate of claim 15, wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein (aka KSP).
Issued claim 18 recites a conjugate comprising the antibody or antigen-binding antibody fragment wherein the variable heavy chain comprises SEQ ID NO: 91 and wherein the variable light chain comprises SEQ ID NO: 95, and a chemotherapeutic (Genus).
The reference variable heavy chain comprises SEQ ID NO: 91, which is identical to instant SEQ ID NO: 91, see sequence alignment below:
ALIGNMENT:
Query Match 100.0%; Score 586; Length 442;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLIQPGGSLRLSCAASGFTFSTSGMHWFRQAPGKGLEWVAYISSSSGFVYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLIQPGGSLRLSCAASGFTFSTSGMHWFRQAPGKGLEWVAYISSSSGFVYA 60
Qy 61 DAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSEAAFWGQGTLVTVSS 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSEAAFWGQGTLVTVSS 113
The reference variable light chain comprises SEQ ID NO: 95, which is identical to instant SEQ ID NO: 95, see sequence alignment below:
ALIGNMENT:
Query Match 100.0%; Score 583; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPLSLPVTPGEPASISCRSQKSRLSRMGITPLNWYLQKPGQSPQLLIYRMSNLA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPLSLPVTPGEPASISCRSQKSRLSRMGITPLNWYLQKPGQSPQLLIYRMSNLA 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCAQFLEYPPTFGQGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCAQFLEYPPTFGQGTKLEIK 112
Issued claim 19 recites the conjugate of claim 18, wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein (aka KSP).
Specification can be used as dictionary for claim terminology, see MPEP 804 II(b)(1). “The specification may be used to learn the meaning of terms and in interpreting the coverage of a claim.” In re Basell Polliolefine Italia S.P.A. 89 USPQ2d 1030 (Fed. Cir. 2008).
The ‘554 patent discloses the antibody or antigen binding fragment thereof conjugated to an inhibitor of kinesin spindle protein (KSP) having the claimed structures (see col. 3 to 7) and reproduced below:
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, which corresponds to instant claims 25, 26, 27, 28, 29, 31, 32, 33 see reference col. 3 to col. 7, in particular.
Regarding instant claim 30, the ‘554 patent teaches
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Regarding claim 75, the ‘554 patent teaches:
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, see col. 19, lines 33-40.
Regarding instant claim 76, the ‘554 patent discloses the extracellular cancer target molecules include EGFR, CD123, HER2, B7H3, TWEAKR, and CXCR5, see col. 7, lines 15-35, col. 19, line
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Regarding claim 77, the anti-EGFR antibody of ‘554 patent that binds to its extracellular target, e.g., EGFR on cancer cells is expected to internalized by the target cancer cell.
Thus, even though the claims being examined were more specific than the ‘554 patent claims (prior art), the species of instant claims were disclosed in the ‘554 patent’s specification, and thus the pending claims were not patently distinct from the ‘544 claims.
Applicants’ arguments filed April 23, 2026 have been fully considered but are not found persuasive.
Applicant respectfully disagrees and traverses the rejection, at least because the Examiner has not established a prima facie case of obviousness double-patenting.
In order to properly assess obviousness double-patenting, the Office is required to follow a two-step analysis as expressly provided in MPEP 804II.B, "the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences. Then the examiner should determine whether those differences render the claims patentably distinct using an anticipation analysis and/or an obviousness analysis. See Pfizer, Inc. v. Teva Pharms. USA, Inc., 518 F.3d 1353, 1363, 86 USPQ2d 1001, 1008 (Fed. Cir. 2008)." The second part of this analysis is analogous to the obviousness inquiry under 35 U.S.C. 103 in the sense that if an earlier claim renders obvious or anticipates a later claim, the later claim is not patentably distinct and is thus invalid for obviousness-type double patenting. UCR Inc v. Accord Healthcare, Inc., 890 F.3d 1313,1323 (Fed. Cir. 2018). Such an analysis also includes an assessment of the factors outlined in Graham v. John Deere. MPEP 804II.B.1. As such, to reject the claims for obviousness double-patenting, the Office must not only identify the differences between the claimed invention and the conflicting claims in the instant application, but also must provide reasons as to why the claims are obvious in view of the claims in the referenced patent. The Examiner's rejection here is incomplete, devoid of any analysis and does not meet the burden to establish a prima facie case.
In particular, the Office merely asserts the two sets of claims are not identical, but "they are not patentably distinct from each other because the only difference is the scope. While not conceding the Examiner's alleged "only difference [in] scope", Applicant respectfully submits that the Office's rejection is totally devoid of the second prong, i.e. why such "only difference in scope" would necessarily render the instant claims [NOT] patentably distinct using an anticipation analysis and/or an obviousness analysis." For example, after acknowledging the scope of the instant claims is "narrower in that the KSP inhibitor of the ADC is limited to a specific structure whereas in the reference application the KSP inhibitor is generic," the Office provides no articulation or analysis on why such difference render a prima facie case of obviousness against the instant claims." See e.g. Office Action, at 15-16.
As a matter of fact, the instant claims 25-35 and 75-77 are directed to conjugates comprising three components: a Markush-specific drug moiety, a linker M, and an antibody or fragment AK. Thus, in order to make them obvious over the '554 Patent, a person of ordinary skills in the art has to be able to arrive from claims 15-20 of the '554 Patent to each and every one of the three elements/components in the instant claims: (1) the Markush drug moiety rich in amino-acid like functional groups; (2) the linker M with a specific carbonyl-containing chain, and (3) the antibody or fragment AK specifically linked to M through either a sulfur atom of a cysteine side chain or nitrogen atom of a lysine side-chain regardless of its sequences. However, the Examiner has totally failed to articulate how to achieve any of the three elements. Therefore, no prima facie case of obvious double patenting rejection has been established.
In summary, claims 25-35 and 75-77 are patentably distinct from the '554 Patent. Reconsideration and withdrawal of the rejections are therefore respectfully requested.
In response, specification can be used as dictionary for claim terminology, see MPEP 804 II(b)(1). “The specification may be used to learn the meaning of terms and in interpreting the coverage of a claim.” In re Basell Polliolefine Italia S.P.A. 89 USPQ2d 1030 (Fed. Cir. 2008).
Issued claim 15 recites a conjugate comprising the antibody or antigen-binding antibody fragment that binds to CXCR5, comprising a variable heavy chain comprising the variable CDR1 sequence of the heavy chain as shown in SEQ ID NO: 92, the variable CDR2 sequence of the heavy chain as shown in SEQ ID NO: 93, and the variable CDR3 sequence of the heavy chain as shown in SEQ ID NO: 94; and a variable light chain comprising the variable CDR1 sequence of the light chain as shown in SEQ ID NO: 96, the variable CDR2 sequence of the light chain as shown in SEQ ID NO: 97, and the variable CDR3 sequence of the light chain as shown in SEQ ID NO: 98, and a chemotherapeutic (generic), whereas instant claims limited the drug to kinesin spindle protein inhibitor (species).
18182,093
11,478,554
SEQ ID NO: 92
TSGMH
TSGMH
SEQ ID NO: 93
YISSSSGFVYADAVKG
YISSSSGFVYADAVKG
SEQ ID NO: 94
SEAAF
SEAAF
SEQ ID NO: 96
RSQKSRLSRMGITPLN
RSQKSRLSRMGITPLN
SEQ ID NO: 97
RMSNLAS
RMSNLAS
SEQ ID NO: 98
AQFLEYPPT
AQFLEYPPT
Heavy chain variable domain
SEQ ID NO: 91
SEQ ID NO: 91
Light chain variable domain
SEQ ID NO: 95
SEQ ID NO: 95
Issued claim 16 recites conjugate of claim 15, wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein (aka KSP).
Issued claim 18 recites a conjugate comprising the antibody or antigen-binding antibody fragment wherein the variable heavy chain comprises SEQ ID NO: 91 and wherein the variable light chain comprises SEQ ID NO: 95, and a chemotherapeutic (Genus).
The reference variable heavy chain comprises SEQ ID NO: 91, which is identical to instant SEQ ID NO: 91, see sequence alignment below:
ALIGNMENT:
Query Match 100.0%; Score 586; Length 442;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLIQPGGSLRLSCAASGFTFSTSGMHWFRQAPGKGLEWVAYISSSSGFVYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLIQPGGSLRLSCAASGFTFSTSGMHWFRQAPGKGLEWVAYISSSSGFVYA 60
Qy 61 DAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSEAAFWGQGTLVTVSS 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DAVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSEAAFWGQGTLVTVSS 113
The reference variable light chain comprises SEQ ID NO: 95, which is identical to instant SEQ ID NO: 95, see sequence alignment below:
ALIGNMENT:
Query Match 100.0%; Score 583; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPLSLPVTPGEPASISCRSQKSRLSRMGITPLNWYLQKPGQSPQLLIYRMSNLA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPLSLPVTPGEPASISCRSQKSRLSRMGITPLNWYLQKPGQSPQLLIYRMSNLA 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCAQFLEYPPTFGQGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCAQFLEYPPTFGQGTKLEIK 112
Issued claim 19 recites the conjugate of claim 18, wherein the chemotherapeutic comprises an inhibitor of kinesin spindle protein (aka KSP). The ‘554 patent discloses the antibody or antigen binding fragment thereof conjugated to an inhibitor of kinesin spindle protein (KSP) having the claimed structures (see col. 3 to 7). The reference ADC having the claimed structures reproduced below:
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, which corresponds to instant claims 25, 26, 27, 28, 29, 31, 32, 33 see reference col. 3 to col. 7, in particular.
Regarding instant claim 30, the ‘554 patent teaches
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Regarding claim 75, the ‘554 patent teaches:
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, see col. 19, lines 33-40.
Regarding instant claim 76, the ‘554 patent discloses the extracellular cancer target molecules include EGFR, CD123, HER2, B7H3, TWEAKR, and CXCR5, see col. 7, lines 15-35, col. 19, line
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Regarding claim 77, the anti-EGFR antibody of ‘554 patent that binds to its extracellular target, e.g., EGFR or anti-CD123 that binds to CD123 on cancer cells is expected to internalized by the target cancer cell after binding.
Thus, even though the claims being examined were more specific than the ‘554 patent claims (prior art), the species of instant claims were disclosed in the ‘554 patent’s specification, and thus the pending claims were not patently distinct from the ‘544 claims.
For these reasons, the rejection is maintained.
Conclusion
No claim is allowed.
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 PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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