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 .
2. Applicant’s response filed on 09/23/2025 is acknowledged.
3. Applicant's election with traverse of Group II and the species of the antibody comprising the 6 CDRs of SEQ ID NOs 2-4 and 6-8; “pyrroloenzodiazepine dimer”, fludarabine and patients about to receive a hematopoietic stem cell transplantation in the reply filed on 09/23/2025 is acknowledged. The Examiner will examine the claims as they read on the antibody of SEQ ID Nos 1 and 5 which comprise the elected CDRs.
The traversal is on the ground(s) that Applicant thinks that it is “not a burden” to search, examine and write an office action on all of claims 1-15, 17-22 and 45-60 in the time allotted for examination. Applicant has cited numerous unpersuasive arguments in support of the non-burdensome nature of examining all of the claims including reference to MPEP 803 and that “electronic search tools available to examiners”. This is not found persuasive. The instant application is a national stage application so the standards of MPEP 1850, 1875 and 1893.03(d) apply. The claims do not have unity of invention because the special technical feature does not make a contribution over the prior art in view of WO 2018/094460 and that showing alone is sufficient for the restriction of the claims as set forth in the restriction requirement mailed on 03/24/2025. It is noted that it is absolutely a burden to search and examine more than one invention, particularly when the inventions are drawn to claims which don’t meet the standards of 112(a) with non-enabled and described claims as set forth in the instant application.
The requirement is still deemed proper and is therefore made FINAL.
4. Claims 1-13 and 47-56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/23/2025.
5. Claims 14-15, 17-22, 45-46 and 57-60 are currently under examination as they read on administering the antibody of SEQ ID NOs 1 and 5 (comprising instant CDRs of SEQ ID NOs 2-4 and 6-8), pyrrolobenzodiazepine dimer and fludarabine to a patient about to receive a hematopoietic stem cell transplantation. The Examiner extended the search to a patient with AML.
6. Applicant’s IDS documents filed on 01/28/2022, 08/01/2022 and 09/24/2025 have been considered.
7. Claim 14 is objected to because of the following informalities: claims 14 is dependent upon non-elected base claim 1. Appropriate correction is required.
8. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 14-15, 17-22, 45-46 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,987,625 in view of Abadir (PTO-892; Reference U), WO 2015/155345 (PTO-892; Reference N) and WO 2018/071576 (PTO-892; Reference O).
Claims 1-13 of U.S. Patent 11,987,625 are directed to an isolated antibody, or antigen binding fragment thereof, which specifically binds to an extracellular domain of CD300f, wherein the antibody, or antigen binding fragment thereof, comprises; (a) a heavy chain variable region comprising a complementarity determining region 1 (CDR1) that comprises the amino acid sequence of SEQ ID NO: 2, a complementarity determining region 2 (CDR2) that comprises the amino acid sequence of SEQ ID NO: 3, and a complementarity determining region 3 (CDR3) that comprises the amino acid sequence of SEQ ID NO: 4; and (b) a light chain variable region comprising a complementarity determining region 1 (CDR1) that comprises the amino acid sequence of SEQ ID NO: 6, a complementarity determining region 2 (CDR2) that comprises the amino acid sequence of SEQ ID NO: 7, and a complementarity determining region 3 (CDR3) that comprises the amino acid sequence of SEQ ID NO: 8 of claim 1; wherein the heavy chain variable region comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 2, a CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 4 of claim 2; wherein the light chain variable region comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 5, and comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 8 of claim 3; wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 1 of claim 4; wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 5 of claim 5; wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 13 of claim 6; wherein the light chain comprises the amino acid sequence of SEQ ID NO: 14 of claim 7; wherein the antibody, or antigen binding fragment thereof, is selected from the group consisting of F(ab′)2, Fab′, Fab, Fv, sFv, scFv, bispecific antibody or BiTE of claim 8; an immunoconjugate comprising the antibody, or antigen binding fragment thereof, of claim 1, coupled to a moiety of claim 9; wherein the moiety is a therapeutic moiety of claim 10; wherein the therapeutic moiety is selected from the group consisting of cytotoxic agent; pro-apoptotic agent; radioisotope; and immunotoxin of claim 11; a pharmaceutical composition comprising the antibody, or antigen binding fragment thereof, of claim 1 of claim 12 and a pharmaceutical composition comprising the immunoconjugate of claim 9 of claim 13.
The claimed invention differs from the prior art in the recitation of administering the immunoconjugate for “treating a condition associated with CD300f expression” of claim 14; “wherein the condition is AML” of claim 15; “a method of preparing a subject for haematopoietic stem cell transplantation” of claim 17; “preparing a subject for hematopoietic stem cell transplantation” of claim 17; “depleting hematopoietic stem and progenitor cells in a subject” of claim 57; administering pyrrolobenzodiazepine moiety of claims 14-15, 18, 46, 58 and 60; pyrrolobenzodiazepine dimer of claims 20 and 59; a lymphodepleting agent of claims 45; and fludarabine of claim 19.
Abadir et al. teaches confirmation of the validity of CD300f as a target on AML in a cohort of 35 AML patients and demonstrated that different CD300f-specific mAbs recognize independent extracellular epitopes. Further, we showed expression of CD300f isoforms by cell lines and primary AMLs is complex and the different isoform expressed affects mAb binding. This work has defined key differences in the extracellular region of CD300f that will help design novel AML therapeutic antibodies to specific isoforms and minimize hematologic toxicity.(In particular, ‘Introduction’, whole document). CD300f is expressed primarily within the myeloid cell series and is present on the myeloid cell populations of healthy PBMC. Three CD300f mAbs bound CD34+CD38− BM-derived HSPC in healthy BM or CB and, importantly, to AML. Multiple isoforms of CD300f will play a role as potential targets and different CD300f antibodies target at least four different epitopes. The reference teaches that there are two possible ways to exploit targeting CD300f in antibody-based therapies against AML with monocytic differentiation. The first method would be to generate a mAb, ADC, or other antibody-based therapeutic derivative that binds preferentially to an exon 4-related epitope. A second way would be to develop chimeric or humanized versions of DCR-2 and UP-D2 for combination therapy in which UP-D2 could be conjugated with a toxic payload as an ADC or developed into another form of therapeutics. These strategies may result in prolonged monocytopenia. (In particular, discussion, whole document)
WO 2015/155345 teaches antibody-drug conjugates (ADCs) more effectively treat cancer while reducing drug-related toxicities by combining the specificity of an antibody with the potency of cytotoxic small molecules. An ADC consists of a warhead that may be a small molecule that has been chemically modified to contain a linker that is used to conjugate the drug to the antibody. Cytotoxicity is induced when the ADC binds to the antigen surface of a target-positive cancer cell, is internalized and trafficked to the lysosome where the warhead is released following either proteolysis of a cleavable linker (for example by cathepsin B found in the lysosome) or through proteolytic degradation of the antibody when a non-cleavable linker is used to attach the warhead to the antibody. The warhead then translocates out of the lysosome and into the cytosol where it can then bind to its target, depending on its mechanism of action. Typically these warheads induce cell cycle arrest which subsequently leads to apoptosis. The reference teaches that a number of classes of cytotoxic agents are known to have potential utility as warheads in ADC molecules including pyrrolobenzodiazepines. The reference teaches that pyrrolobenzodiazepine dimer (PBD) warhead translocates to the nucleus where it crosslinks DNA, preventing replication during mitosis, damaging DNA by inducing single strand breaks and subsequently leading to apoptosis.
WO 2018/071576 teaches use of inhibitors of CD300f with additional chemotherapeutic agents, including fludarabine, to treat tumors, including hematological tumors such as AML. (In particular, whole document).
It would have been obvious to have used the isolated antibody which specifically binds to an extracellular domain of CD300f of U.S. Patent 11,987,625 with pyrrolobenzodiazepine dimer and fludarabine to treat a condition associated with CD300f expression, including AML, including by preparing a subject for hematopoietic stem cell transplantation by depleting hematopoietic stem and progenitor cells in a subject because the art of Abadir et al. teaches that CD300f is expressed primarily within the myeloid cell series and is present on the myeloid cell populations of healthy PBMC. Three CD300f mAbs bound CD34+CD38− BM-derived HSPC in healthy BM or CB and, importantly, to AML. Multiple isoforms of CD300f will play a role as potential targets and different CD300f antibodies target at least four different epitopes and that CD300f can be targeted in antibody-based therapies against AML with monocytic differentiation by generating an ADC that binds preferentially to an exon 4-related epitope to result in prolonged monocytopenia. (In particular, discussion, whole document). It would have been obvious to have used the pyrrolobenzodiazepine dimer and fludarabine because the art of WO 2015/155345 teaches the use of pyrrolobenzodiazepine dimer in ADCs which target tumors and WO 2018/071576 teaches use of inhibitors of CD300f with additional chemotherapeutic agents, including fludarabine, to treat tumors, including hematological tumors such as AML. (In particular, whole document). It would have been obvious to have combined all three of these components to arrive at the claimed invention. Furthermore, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). The same is true for combining three different elements of the claimed methods. The combination is obvious to arrive at the claimed method. The combination flows logically from the individual teachings of the prior art.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
10. Claims 14-15, 17-22, 45-46 and 57-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-44 of copending Application No. 18/652,625 in view of Abadir (PTO-892; Reference U), WO 2015/155345 (PTO-892; Reference N) and WO 2018/071576 (PTO-892; Reference O).
Claims 23-44 of U.S. Application 18/652,625 are directed to a method of treating a condition associated with CD300f expression in a subject in need thereof, comprising administering to the subject an effective amount of an antibody, or antigen binding fragment thereof, which specifically binds to an extracellular domain of CD300f, wherein the antibody, or antigen binding fragment thereof, comprises: (a) a heavy chain variable region comprising a complementarity determining region 1 (CDR1) that comprises the amino acid sequence of SEQ ID NO: 2, a complementarity determining region 2 (CDR2) that comprises an amino acid sequence of SEQ ID NO: 3, and a complementarity determining region 3 (CDR3) that comprises an amino acid sequence of SEQ ID NO: 4; and (b) a light chain variable region comprising a complementarity determining region 1 (CDR1) that comprises an amino acid sequence of SEQ ID NO: 6, a complementarity determining region 2 (CDR2) that comprises an amino acid sequence of SEQ ID NO: 7, and a complementarity determining region 3 (CDR3) that comprises an amino acid sequence of SEQ ID NO: 8 of claim 23; wherein the heavy chain variable region comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 2, a CDR2 comprising an amino acid sequence of SEQ ID NO: 3, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 4 of claim 24; wherein the light chain variable region comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 5, and comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a CDR2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 8 of claim 25; wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 1 of claim 26; wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 5 of claim 27; wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 13 of claim 28; wherein the light chain comprises the amino acid sequence of SEQ ID NO: 14 of claim 29; wherein the antibody, or antigen binding fragment thereof, is selected from the group consisting of F(ab')2, Fab', Fab, Fv, sFv, scFv, bispecific antibody or BiTE of claim 30; wherein the condition is AML of claim 31; a method of treating a condition associated with CD300f expression in a subject in need thereof, comprising administering to the subject an effective amount of an immunoconjugate comprising an antibody, or antigen binding fragment thereof, coupled to a moiety, wherein the antibody, or antigen binding fragment thereof, comprises: (a) a heavy chain variable region comprising a complementarity determining region 1 (CDR1) that comprises the amino acid sequence of SEQ ID NO: 2, a complementarity determining region 2 (CDR2) that comprises an amino acid sequence of SEQ ID NO: 3, and a complementarity determining region 3 (CDR3) that comprises an amino acid sequence of SEQ ID NO: 4; and (b) a light chain variable region comprising a complementarity determining region 1 (CDR1) that comprises an amino acid sequence of SEQ ID NO: 6, a complementarity determining region 2 (CDR2) that comprises an amino acid sequence of SEQ ID NO: 7, and a complementarity determining region 3 (CDR3) that comprises an amino acid sequence of SEQ ID NO: 8 of claim 32; wherein the heavy chain variable region comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 1, and comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 2, a CDR2 comprising an amino acid sequence of SEQ ID NO: 3, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 4 of claim 33; wherein the light chain variable region comprises an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 5, and comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 6, a CDR2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 8 of claim 34; wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 1 of claim 35; wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 5 of claim 36; wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 13 of claim 37; wherein the light chain comprises the amino acid sequence of SEQ ID NO: 14 of claim 38; wherein the antibody, or antigen binding fragment thereof, is selected from the group consisting of F(ab')2, Fab', Fab, Fv, sFv, scFv, bispecific antibody or BiTE of claim 39; wherein the moiety is a therapeutic moiety of claim 40; wherein the therapeutic moiety is selected from the group consisting of cytotoxic agent; pro-apoptotic agent; radioisotope; and immunotoxin of claim 41; wherein the condition is AML of claim 42; a hybridoma deposited under the Budapest Treaty at CellBank Australia, and designated accession number CBA20160029 of claim 43; and a monoclonal antibody produced by the hybridoma of claim 43.
Reference SEQ ID NOs 1-8 are 100% sequence identical to instant SEQ ID NOs 1-8:
The recitation of “depleting hematopoietic stem and progenitor cells in a subject” of claim 57 and “preparing a subject for hematopoietic stem cell transplantation” of claim 17 is inherent in the reference method. The same composition is being given the same patient population for the same result.
The reference teachings anticipate the claimed invention.
The claimed invention differs from the prior art in the recitation of administering pyrrolobenzodiazepine moiety of claims 14-15, 18, 46, 58 and 60; pyrrolobenzodiazepine dimer of claims 20 and 59; a lymphodepleting agent of claims 45; and fludarabine of claim 19.
Abadir et al. teaches confirmation of the validity of CD300f as a target on AML in a cohort of 35 AML patients and demonstrated that different CD300f-specific mAbs recognize independent extracellular epitopes. Further, we showed expression of CD300f isoforms by cell lines and primary AMLs is complex and the different isoform expressed affects mAb binding. This work has defined key differences in the extracellular region of CD300f that will help design novel AML therapeutic antibodies to specific isoforms and minimize hematologic toxicity.(In particular, ‘Introduction’, whole document). CD300f is expressed primarily within the myeloid cell series and is present on the myeloid cell populations of healthy PBMC. Three CD300f mAbs bound CD34+CD38− BM-derived HSPC in healthy BM or CB and, importantly, to AML. Multiple isoforms of CD300f will play a role as potential targets and different CD300f antibodies target at least four different epitopes. The reference teaches that there are two possible ways to exploit targeting CD300f in antibody-based therapies against AML with monocytic differentiation. The first method would be to generate a mAb, ADC, or other antibody-based therapeutic derivative that binds preferentially to an exon 4-related epitope. A second way would be to develop chimeric or humanized versions of DCR-2 and UP-D2 for combination therapy in which UP-D2 could be conjugated with a toxic payload as an ADC or developed into another form of therapeutics. These strategies may result in prolonged monocytopenia. (In particular, discussion, whole document)
WO 2015/155345 teaches antibody-drug conjugates (ADCs) more effectively treat cancer while reducing drug-related toxicities by combining the specificity of an antibody with the potency of cytotoxic small molecules. An ADC consists of a warhead that may be a small molecule that has been chemically modified to contain a linker that is used to conjugate the drug to the antibody. Cytotoxicity is induced when the ADC binds to the antigen surface of a target-positive cancer cell, is internalized and trafficked to the lysosome where the warhead is released following either proteolysis of a cleavable linker (for example by cathepsin B found in the lysosome) or through proteolytic degradation of the antibody when a non-cleavable linker is used to attach the warhead to the antibody. The warhead then translocates out of the lysosome and into the cytosol where it can then bind to its target, depending on its mechanism of action. Typically these warheads induce cell cycle arrest which subsequently leads to apoptosis. The reference teaches that a number of classes of cytotoxic agents are known to have potential utility as warheads in ADC molecules including pyrrolobenzodiazepines. The reference teaches that pyrrolobenzodiazepine dimer (PBD) warhead translocates to the nucleus where it crosslinks DNA, preventing replication during mitosis, damaging DNA by inducing single strand breaks and subsequently leading to apoptosis.
WO 2018/071576 teaches use of inhibitors of CD300f with additional chemotherapeutic agents, including fludarabine, to treat tumors, including hematological tumors such as AML. (In particular, whole document).
It would have been obvious to have used the isolated antibody which specifically binds to an extracellular domain of CD300f of U.S. Patent Application 18/652,625 with pyrrolobenzodiazepine dimer and fludarabine to treat a condition associated with CD300f expression, including AML, including by preparing a subject for hematopoietic stem cell transplantation by depleting hematopoietic stem and progenitor cells in a subject because the art of Abadir et al. teaches that CD300f is expressed primarily within the myeloid cell series and is present on the myeloid cell populations of healthy PBMC. Three CD300f mAbs bound CD34+CD38− BM-derived HSPC in healthy BM or CB and, importantly, to AML. Multiple isoforms of CD300f will play a role as potential targets and different CD300f antibodies target at least four different epitopes and that CD300f can be targeted in antibody-based therapies against AML with monocytic differentiation by generating an ADC that binds preferentially to an exon 4-related epitope to result in prolonged monocytopenia. (In particular, discussion, whole document). It would have been obvious to have used the pyrrolobenzodiazepine dimer and fludarabine because the art of WO 2015/155345 teaches the use of pyrrolobenzodiazepine dimer in ADCs which target tumors and WO 2018/071576 teaches use of inhibitors of CD300f with additional chemotherapeutic agents, including fludarabine, to treat tumors, including hematological tumors such as AML. (In particular, whole document). It would have been obvious to have combined all three of these components to arrive at the claimed invention. Furthermore, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). The same is true for combining three different elements of the claimed methods. The combination is obvious to arrive at the claimed method. The combination flows logically from the individual teachings of the prior art.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
11. The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
12. Claims 14, 17-22, 45-46 and 57-60 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 : treating AML by administering the immunoconjugate of claim 1, the specification does not reasonably provide enablement for treating “a condition associated with CD300F expression” by administering the immunoconjugate of claim 1; or the administration of “a immunoconjugate comprising an antibody or an antigen binding fragment thereof, linked to at least one cytotoxic agent, wherein the antibody or antigen binding fragment thereof, specifically binds CD300f” for any purpose. 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 and use the invention commensurate in scope with these claims. The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification is not enabled for the use of “a immunoconjugate comprising an antibody or an antigen binding fragment thereof, linked to at least one cytotoxic agent, wherein the antibody or antigen binding fragment thereof, specifically binds CD300f”. The claims encompass any antibody which binds to CD300f and any cytotoxic agent.
The art of Abadir et al. (PTO-892; Reference U) teaches that expression of CD300f is complex and the different isoform expressed affects mAb binding. The reference teaches that their work defined key differences in the extracellular region of CD300f that will help design novel AML therapeutic antibodies to specific isoforms and minimize hematologic toxicity.(In particular, ‘Introduction’, whole document). Multiple isoforms of CD300f will play a role as potential targets and different CD300f antibodies target at least four different epitopes. An antibody-based therapeutic derivative should binds preferentially to an exon 4-related epitope. (In particular, discussion, whole document).
As such, not any CD300f or any immunoconjugate would be able to be used in the claimed invention without undue experimentation.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention
13. Claims 17-21, 45 and 57-60 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.
Applicant is in possession of: treating AML by administering the immunoconjugate of claim 1.
Applicant is not in possession of: treating “a condition associated with CD300F expression” by administering the immunoconjugate of claim 1; or the administration of “a immunoconjugate comprising an antibody or an antigen binding fragment thereof, linked to at least one cytotoxic agent, wherein the antibody or antigen binding fragment thereof, specifically binds CD300f”.
The claims encompass any immunoconjugate with any anti-CD300f antibodies and any cytotoxic agent.
Conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
The specification has neither demonstrated a structure function relationship nor provided a representative number of species of antibodies with the recited binding specificity or many recited functions.
The specification must set forth the structural features that allow one of ordinary skill in the art to identify and produce the recited antibodies and immunoconjugates. In the instant case, definition by function does not suffice to define the genus because it is only an indication of what the antibodies and immunoconjugates do, rather than what they are.
It is well established in the art that it is highly unpredictable which changes in amino acid sequence can be made in complementarity determining regions (CDRs) of a parental antibody such that the derived antibody retains the binding specificity and affinity of the parent antibody.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function.
Antibody specificity for a particular antigen does not correlate with any particular structure for the antibodies themselves. It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is unpredictable which antibodies with which structures would exhibit the recited binding functions.
"Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the antibodies and immunoconjugtes encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
MPEP § 2163 sets forth guidelines for the examination of patent applications under the 35 U.S.C. § 112, 1st paragraph, “Written Description” requirement:
A "representative number of species" means that the species which are adequately described are representative of the entire 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when…the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.)….
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation."
The potential scope of the genus encompassed in the breadth of the claims is enormous. Claims 17-20, 45 and 57-59 recite no antibody structure whatsoever so it reads on any antibody structure with the recited functions. While one could enumerate the thousands to millions of sequences potentially encompassed in the breadth of these claims with the aid of computer, simply doing so would not bring the skilled artisan any closer to demonstrating possession of the subset of antibodies with the claimed binding specificity and functions.
Applicant should amend the claims to recite antibodies with all 6 CDRs specified which were actually produced in the specification which have the claimed binding specificity and functions recited in the claims. The description of the antibodies which Applicant actually produced is not sufficient to provide adequate written description for the vast genus of antibodies recited in the claims. There is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed antibodies to demonstrate possession and there are not a sufficient number of species which are encompassed by the claimed invention .
U.S. Court of Appeals for the Federal Circuit recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed,
35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen"
test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. , the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872
F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345
(Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly\ characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Id.
The specification does not provide adequate written description of the claimed invention.
The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111
(Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. In the instant application, the amino acid sequence itself or isolated protein is required. See Fiers v. Revel, 25 USPQ 2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. In view of the aforementioned problems regarding description of the claimed invention, the specification does not provide an adequate written description of the invention claimed herein.
See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398,
1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225
(Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different vertebrates or mammals, but had only described a single species of cDNA which encoded rat insulin. The court held that only the nucleic acids species described in the specification (i.e. nucleic acids encoding rat insulin) met the description requirement and that the inventors were not entitled to a claim encompassing a genus of nucleic acids encoding insulin from other vertebrates, mammals or humans, id. at 1240. The Federal Circuit has held that if an inventor is "unable to envision the detailed constitution of a gene so as to distinguish it from other materials.
. .conception has not been achieved until reduction to practice has occurred", Amgen, Inc. v.
Chugai Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed to the decision of The Regents of the University of California v. Eli Lilly and Company (CAFC,
July 1997) wherein is stated: "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, naming 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 that material. Thus, as we have previously held, a cDNA is not defined or described by the mere name "cDNA," even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See
Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed antibodies and immunoconjugates to demonstrate possession.
14. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
15. Claims 17, 21-22, 45 and 57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/094460 (IDS filed on 01/28/2022).
WO 2018/094460 teaches a method of treating a condition associated with CD300f expression in a subject in need thereof, comprising administering to the subject an effective amount of an DCR-2 antibody or an immunoconjugate thereof. Accordingly, a further aspect provides a method of treating a condition associated with CD300f expression, such as AML, comprising administering to a subject in need thereof an effective amount of an DCR-2 antibody, or antigen binding fragment thereof, that specifically binds CD300f, or an immunoconjugate thereof, wherein the antibody, antigen binding fragment thereof, comprises:
The reference teaches that the antibody or antigen binding fragment thereof may be coupled to a moiety. Accordingly, another aspect provides an immunoconjugate comprising:
(a) a heavy chain variable region which comprises:
(i) an amino acid sequence that is at least 70% identical, typically at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical, to the amino acid sequence represented by SEQ ID NO: 1 ; and/or
(ii) a complementarity determining region 1 (CDR1 ) comprising the amino acid sequence represented by SEQ ID NO: 2, a complementarity determining region 2 (CDR2) comprising the amino acid sequence represented by SEQ ID NO: 3, and/or a complementarity determining region 3 (CDR3) comprising the amino acid sequence represented by SEQ ID NO: 4; and/or
(b) a light chain variable region which comprises:
(i) an amino acid sequence that is at least 70% identical, typically at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical, to the amino acid sequence represented by SEQ ID NO: 5; or
(ii) a complementarity determining region 1 (CDR1 ) comprising the amino acid sequence represented by SEQ ID NO: 6, a complementarity determining region 2
(CDR2) comprising the amino acid sequence represented by SEQ ID NO: 7, and/or a complementarity determining region 3 (CDR3) comprising the amino acid sequence represented by SEQ ID NO: 8,
wherein the antibody or antigen binding fragment thereof is coupled to a moiety.
The moiety can be directly or indirectly coupled to the antibody, or antigen binding fragment thereof (e.g., can comprise a linker in the case of indirect binding). Examples of moieties include, a radioisotope (e.g., iodine-131 , yttrium-90 or indium-1 1 1 ), a detectable label (e.g., a fluorophore or a fluorescent nanocrystal), a therapeutic compound (e.g., a chemotherapeutic or an anti-inflammatory), a colloid (e.g., gold), a toxin (e.g., ricin), a nucleic acid, a peptide (e.g., a serum albumin binding peptide), a protein (e.g., a protein comprising an antigen binding domain of an antibody or serum albumin), a compound that increases the half-life of the antibody or antigen binding protein in a subject (e.g., polyethylene glycol or other water soluble polymer having this activity) or mixtures thereof. Methods for coupling moieties to proteins are known in the art and described in, for example, WO2010/059821 .
In one embodiment, the moiety is a therapeutic moiety and/or a diagnostic moiety.
WO 2018/094460 teaches in one embodiment, the moiety is a therapeutic moiety. A therapeutic moiety is a compound, molecule or atom which is useful in the treatment of a disease or condition. Examples of therapeutic moieties include: drugs, such as cytotoxic agents, such as chemotherapeutic agents; pro-apoptotic agents; radioisotopes; immunotoxins. A cytotoxic agent is a compound which is toxic to cells. Examples of cytotoxic agents include cytochalasin B, gramicidin, emetine, tenoposide, colchicine, duocarmycins, calicheamicins, maytansines, doxorubicin, cyclophosphamide, methotrexate, mustine, vincristine, procarbzine, prednisolone, bleomycin, vinblastine, dacarbazine, cyclophosphamide (lymphodepleting agent), Procarbazine, Paclitaxel, Irinotecan, Gemcitabine, Fluorouracil, Cytarabine, ozogamicin, adriamycin, etoposide, melphalan, mitomycin C, chloramuil, daunorubicin, monomethyl-auristatin E (MMAE). Examples of radioisotopes include phosphorus-32, copper-67, arsenic-77, rhodium-105, palladium-109, silver-1 1 1 , tin-1221 , iodine-125, iodine-131 , holmium-166, lutetium-177, rhenium-186, iridium-194, gold-199, astatium-21 1 , yttrium-90, and bismuth-212. Examples of immunotoxins are described in, for example, Wayne et al. (2016) Blood, 123: 2470-2477, and i