DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim 13 has been canceled. Claims 3, 4, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 17 have been amended. Claims 18-21 have been added. Claims 1-12 and 14-21 are pending and examined on the merits.
Applicant is reminded that 37 C.F.R. 1.121©(2) states: The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. The deleted versus added matter is not easily perceived in claims 7, 14 which are being interpreted as dependent upon claim 4.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 5, 6, 7, 8, 9, 10, 11, 12-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
(A)Regarding claim 15, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
(B It is unclear if “stereoisomer thereof” refers to only to stereocenters in “Abu-M-B-L” and side chain “G” in claims 4, 5, 6, 7, or if the stereocenters which are part of the drug “D” are included as in claims 7-9. For purpose of examination, both alternatives will be considered.
(c) the recitation of “or the antibody or antigen-binding unit thereof is humanized” on page 41, line 9 is vague and indefinite because it is unclear if this is a separate embodiment to the antibody of the generic anti-B7H3 conjugate in claim 4, or if this refers to the preceding antibody in claim 11 on page 41, lines 6-8 (“after an amino acid sequence set forth in SEQ ID NO:29;”
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.
Claims 1-12 and 14-21 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
(A)Claims 1-12 and 14-21 are reliant in part on a “salt” or “solvate” of anti-B7-H3 drug conjugates.
When given the broadest reasonable interpretation, salts, and solvates encompass solid forms of the anti-B7-H3 drug conjugates of claim 1.
The specification fails to provide any teachings for how to make the solid forms of salts, or solvates of the instant antibody conjugates. Matheus et al (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 1-10 (subscript “p”) in claim 4.
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 1-10. 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, 2015, Vol. 548, pp. 682-688, 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 dolastatin, auristatin, maytansinoid, MMAE, MMAF, calicheamicin, duocarmycin, PBD, irinotecan, exatecan, ,camptothecins, SN38, 22-hydroxyaccuminitine, topotecan , lurotecan, belotecan, homosilatecan, etc., on the ability of the antibody to go into a crystal lattice of a salt is unknown.
The instant claims also require a solvate of an anti-B7-H3 antibody conjugate. Matheus et al (U.S. 7,960,516) teach that solvates are a solid form having adductions of inert solvent molecules, and that solvates include hydrates such as monohydrates, dihydrates or alcoholates (column 10, lines 37-43).
The specification has not provided the reagents or conditions for the formation of a single salt, or solvate for the anti-B7-H3conjugate encompassed by the claims. It would not be expected that the conditions disclosed for the formation of hydrates of unconjugated cetuximab or Mab h425 would be the same reagents or conditions for the formation of salts, hydrates or solvates for the instant B7-H3 conjugates to the multitude of drugs encompassed by the claimed conjugates.. Thus, one of skill in the art would be subject to undue experimentation in order to make the anti-B7-H3 conjugates in a solid format as a salt or the solvates.
(B) disease prevention
Claims 14-16 are drawn in part to the prevention of a disease by the administration of the inventive antibody-drug conjugates to a subject in need thereof. When given the broadest reasonable interpretation, the “subject” includes humans and non-experimental animals. In order to prevent a disease such as a tumor, autoimmune disease, inflammatory disease or infectious disease, the antibody-drug conjugate must be preset in the patient at a therapeutically effective amount prior to the start of the disease or the exposure to an infectious agent. The instant antibody-drug conjugates have a finite lifetime in vivo and the window of the therapeutically effective amount will be shorter than the lifetime of the conjugate in vivo. Thus, in order to prevent the disease in a human or non-experimental animal it would be necessary to know in advance when a naturally occurring disease would occur in the future so as to provide the therapeutically effective amount to the patient prior to the disease. Accordingly, one of skill in the art would be subject to undue experimentation without reasonable expectation of success in order to practice the methods of claims 14 and 15 for the prevention of a disease.
(C)Treatment of a disease, such as a cancer or tumor, a musculoskeletal disease, a genitourinary disease, a nervous system disease or a digestive system disease,, without regard to the status of B7-H3 expression on the surface of the pathological cells.
Claims 14 is drawn, in part, to the treatment of a disease, comprising the administration of the antibody-conjugate of claim 4. Claim 15 lists the specific diseases of the patient in need thereof. Claim 15 includes the treatment of tumors which are positive for B7-H3 expression and diseases and tumors associated with abnormal B7-H3 expression. When given the broadest reasonable interpretation, abnormal expression can include low or no expression of B7-H3. Regarding the tumors listed by site of occurrence, Castellanos et al (Am. J. Clin. Immunol., 2017, Vol. 6, 00. 66-75) teaches that 39% (32 out of 82) to over 80% of breast tumor samples are reported as having positive expression of B7H3 (page 70, lines 6-11 and 17-19 under the heading “B7-H3 in breast cancer”) and that for clear cell renal cancer, 95% of the tumor specimens were found to be positive (page 70, lines 8-14). Thus, it is not to be expected that all of the cancer types treated by the methods of claims 14 and 15 would exhibit B7-H3 protein expression. Further the specification provides no guidance or teachings regarding the expression of B7H3 in the broadly claimed a musculoskeletal disease, a genitourinary disease, a nervous system disease or a digestive system disease which are not restricted to cancers.
Without the B7-H3 target being expressed on pathological cells, one of skill in the art would be subject to undue experimentation without reasonable expectation of success in the treatment of cancers, musculoskeletal disease, a genitourinary disease, a nervous system disease or a digestive system disease.
(D) treatment of autoimmune disease, an inflammatory disease and an infectious disease
Regarding the treatment of autoimmune disease, the specification provides no teachings or guidance for the treatment of such. With regard to systemic lupus erythematosus, Zheng et al (Cell Death and disease, 2019, Vol. 10, No. 393, 11 pages) teach that mice deficient in B7-H3 or treated with a B7-H3 specific antibody produced significantly higher level of anti-DNA autoantibodies and more sever glomerulonephritis than wild-type mice (abstract) which would indicate to one of skill in the art that B7-H3 expression was associated with a less sever disease. However, Zheng et al also teach that immunizing mice with DNA-pulsed dendritic cells expressing B7H3 induced sever lupus symptoms, which would indicate that B7H3 expression was detrimental. It appears that the art is immature as to the function of B7H3 in an autoimmune disease, such as SLE. The specification provides no guidance or objective evidence that systemic administration of the anti-B7H3 conjugate of claim 4 to a subject with lupus would be therapeutic for said patient.
Regarding the treatment of inflammatory diseases and infectious diseases, the specification provides no teachings or guidance for the treatment of such diseases. Luo et al (PLoS one, 2015, Vol. 10, No. 6, e0130126) teach that a B7H3 deficient mouse strain in an experimental autoimmune encephalomyelitis model as well as a collagen-induced arthritis model demonstrate significantly less inflammation, decreased pathogenesis and limited disease possession , but that the B7H3 deficient mouse strain demonstrates sever-ovalbumin-induced asthma, with characteristic eosinophilic infiltrates, increased Il-5 and Il-13 and elevated IgE anti-OVA antibodies in the blood (abstract). Luo et al suggest that B7-H3 has a costimulatory function of Th1/Th17 axis, but a co-inhibitory function of Th2 responses(abstract). Luo et al posit that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progress. One of skill in the art would understand that this applies to the treatment of infectious diseases as well. It appears that the art is immature as to the function of B7H3 in an inflammatory, disease such as CIA and infectious disease. The specification provides no guidance or objective evidence that systemic administration of the anti-B7H3 conjugate of claim 4 to a subject with arthritis or an infection would be therapeutic for said patient.
Claims 3-12 and 14-21 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
(A)Claims 4-12, and 14-21 are reliant in part on a genus of stereoisomers of the antibody-drug conjugates of formula I, antibody-drug conjugates of Formula I-1, I-2, I-2-1, I-3, I-4, I-4-1. I-5, I-5-1, I-6, I-6-1, I-7, I-7-1, , I-8, I-8-1, I-9, I-9-1, I-10, I-10-1, I-11, I-11-1, the drug of claim 7,and 8; and the antibody-drug conjugates of claim 9, including Formulas I-12, I-12-1, I-13, I-13-1, I-14, I-14-1, I-15, I-15-1, I-16, I-16-1, I-17, I-17-1, I-18, I-1-1, I-19, I-19-1, I-20, I-20-1 I22, I-22-1, I-23, I-23-1, I-24, I-24-1, I-25, I-25-1.
Section 2163 of the M.P.E.P. states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). 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.
When given the broadest reasonable interpretation, a “stereoisomer” includes a mirror image isomer as well as diastereomers which vary at each chiral center. The specification shows reduction to practice of a single diastereomer for each of formulas I-2-1, I-4-1. I-5-1, I-6-1, I-7-1, I-8-1, I-9-1, I-10-1, I-11-1, I-12-1, I-13-1, I-14-1, I-15-1, I-16-1, I-17-1, I-18-1, I-19-1, I-20-1; I-22-1, I-23-1, I-24-1, I-25-1. These diastereomers fail to describe the genus of stereoisomers for each of the formulas because the genus includes variations at each chiral center for all of Abu-M-B(G)-L-D which includes chiral centers present in the drug molecule and the specification describes only a single diastereomer for all the formulas Abu-M-B(G)-L and a few of the drug molecules as in claim 8, for example. One of skill in the art would reasonably conclude that applicant was not in possession of the genus of “stereoisomers” for the antibody-drug conjugates at the time of filing.
(B1)The specification evidences reduction to practice of Abu-M-B(G)-L-D wherein R is -CH2-, FF is
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and the drug,
D is
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or
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wherein the main variation is the number of PEG groups attached to the G moiety:
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63
99
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which varies in the examples in the specification from n=4, 8, 10, 12, 16, 18, and 24. However, the claimed genus of Abu-M-B(G)-L-D is highly variant encompassing a multitude of drugs.
(B2)Claims 3 and 7 are reliant in part on a genus of derivatives of exatecan::
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wherein:
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Further, “M” is claimed as
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but only R of a single CH2 is reduced to practice.
Also, FF is claimed as three alternatives:
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or
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574
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but only the “FF” first structure having an Rf which is H, and not the alternatives named above, has been reduced to practice.
Written description issues may arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process (Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species; MPEP 2162.1(A)).
The criteria for a “representative number of species” to be described requires that the species which are reduced to practice are representative of the entire genus. The description of the conjugates reduced to practice providing only a single example or a limited number of moieties required in the conjugate structure are not representative of the conjugates required in the instant claims and thus, it cannot be concluded that 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.").
Regarding the description of the genus by partial structure combined with a specific function, the specification fails to provide such a correlation. It would be expected that the plethora of different X1, X2 and X4 groups attached to different parts of the exatecan molecule would result in conjugates with different properties resulting in the drug being delivered with different kinetics under different microenvironmental conditions. It would be expected that the plethora of different R groups of the M moiety can influence the formation and stability of the conjugate formed by an antibody cysteine reacting with the precursors maleimide. It would be expected that the two alternatives for the FF moiety not reduced to practice would result in conjugates with different properties from that of the exemplified alternative, the different properties resulting from the mechanism of drug release after internalization into the lysosome.
Thus, the specification fails to provide adequate written description for the genus of conjugates claimed and does not reasonably convey to one of skill in the art that he inventors, at the time the application was filed, had possession of the genus of conjugates, pharmaceutical composition comprising said conjugates and methods of treatment comprising the administration of said conjugates.
(C)the genus of anti-B7H3 antibodies.
Claim 10 encompasses the ADC of claim 4 which is characterized by the anti-B7H3 antibody as having the three heavy chain CDRs of SEQ ID NO: 6-8 or as an alternative, the light chain CDR1 of SEQ ID NO: 9-13, the light chain CDR2 of SEQ ID NO: 14-18 and the light chain CDR3 of SEQ ID NO: 19-23.
The properly spaced CDRs in an antibody heavy and light chain define the antibody paratope which is responsible for the recognition of a specific epitope. The specification defines the CDRs for the heavy and light chains of the inventive anti-B7H3 antibody as comprising SEQ ID NO: 6-8 in the heavy chain and SEQ ID NO: 9-13 as the light chain CDR1, SEQ ID NO: 14-18 as the light chain CDR2 and SEQ ID NO: 19-23 as the light chain CDR3. In claim 10, the heavy chain is claimed as a separate alternative to the light chain with the light chain and heavy chain leaving the light chain as undefined in the first part of the claim , and the heavy chain undefined in the second part of the claim. One of skill in the art would not be able to envisage an alternative light chain of a B7H3 binding antibody that did not encompass the CDR regions taught by the specification to be part of the light chain of anti-B7H3 antibody. Conversely, one of skill in the art would not be able to envisage an alternative heavy chain of a B7H3 binding antibody that did not encompass the CDR regions taught by the specification to be part of the heavy chain of anti-B7H3 antibody. The written description of SEQ ID NO: 6-8 in the heavy chain and SEQ ID NO: 9-13 as the light chain CDR1, SEQ ID NO: 14-18 as the light chain CDR2 and SEQ ID NO: 19-23 as the light chain CDR3 fails to describe the genus of antibodies having a light chain which is not limited by the light chain CDR1, SEQ ID NO: 14-18 as the light chain CDR2 and SEQ ID NO: 19-23 as the light chain CDR3 and a heavy chain which was not limited by SEQ ID NO: 6-8.
Claim 11, page 40, lines 7-12 is reliant in part to the anti-B7H3 antibody of claim 10, wherein the heavy chain variable region is an amino acid sequence of any one of SEQ ID NO: 24 and 35-38 or an amino acid sequence having 80-90% identity to any one of SEQ ID NO: 24 and 35-38, or an amino acid sequence having one or more conservative substitutions relative to any one of SEQ ID NO: 24 and 35-38, all of the foresaid being alternatives (“or”) to the light chain variable region comprising an amino acid sequence of any one of SEQ ID NO: 25-29 and 39-41 or an amino acid sequence having at least 80 or 90% identity to any one of SEQID NO: 25-29 and 39-41 (lines 13-18).
Thus claim 11 is reliant on a genus of anti-B7H3 antibodies characterized as comprising a heavy chain variable region comprising any one of SEQ ID NO: 24 and 35-38 without any limitations as to the CDR sequences of the light chain, and as an alternative anti-B7H3 antibodies characterized as comprising a heavy chain variable region comprising any one of SEQ ID NO: 25-29 and 39-41 without any limitations as to the CDR sequences of the heavy chain. One of skill in the art would not be able to envisage an alternative light chain of a B7H3 binding antibody that did not encompass the CDR regions taught by the specification to be part of the light chain of anti-B7H3 antibody. Conversely, one of skill in the art would not be able to envisage an alternative heavy chain of a B7H3 binding antibody that did not encompass the CDR regions taught by the specification to be part of the heavy chain of anti-B7H3 antibody. Further, the genus of ant-B7H3 antibodies encompassed by claim 11 includes
(a)a heavy chain variable region having at least 80% or 90% identity to any one of SEQ ID NO: 24 and 35-38 or an amino acid sequence having one or more conservative amino acid substitutions relative to any one of SEQ ID NO: 24 and 35-38 paired with a light chain that is
(i) undefined in terms of CDR sequence;
(ii)a light chain having at least 80% or 90% identity compared with any one of SEQ ID NO: 25-29 and 39-41, or an amino acid sequence having one or more conservative amino acid substitutions relative to any one of SEQ ID NO: 25-29 and 39-41;
(iii)a light chain comprising an amio acid sequence set forth in any of SEQ ID NO: 25-29 and 39-41.
(b) a light chain variable region having at least 80% or 90% identity to any one of SEQ ID NO: 25-29 and 39-41 or an amino acid sequence having one or more conservative amino acid substitutions relative to any one of SEQ ID NO: 25-29 and 39-41 paired with a heavy chain that is
(i) undefined in terms of CDR sequence;
(ii)a heavy chain having at least 80% or 90% identity compared with any one of SEQ ID NO:24 and 35-38, or an amino acid sequence having one or more conservative amino acid substitutions relative to any one of SEQ ID NO: 24 and 35-38;
(iii)a heavy chain comprising an amio acid sequence set forth in any of SEQ ID NO: 24 and 35-38.
It is further noted that the genus comprising the heavy and light chain variants having at least 80 or 90% sequence identity or having one or more conservative amino acid substitutions does not exclude substitutions within the CDR regions of the variant heavy and/or light chains. For all the above combinations, one of skill in the art would not be able to envisage an alternative light chain of a B7H3 binding antibody that did not encompass the CDR regions taught by the specification to be part of the light chain of anti-B7H3 antibody. Conversely, one of skill in the art would not be able to envisage an alternative heavy chain of a B7H3 binding antibody that did not encompass the CDR regions taught by the specification to be part of the heavy chain of anti-B7H3 antibody.
One of skill in the art would reasonably conclude that applicant was not in possession of the genus of anti-B7H3 antibodies of claims 10 and 11. .
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-12 and 14-21 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Tang et al (WO2022/253284) as evidenced by U.S.2024/0269315 (English Language translation).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Tang et al disclose antibody-drug conjugates wherein the antibody is an anti-B7-H3 antibody having the heavy chain of SEQ ID NO: 21 and the light chain of SEQ ID NO: 22 (paragraphs [0385]-[0386]) which meets the limitations of clams 1-3, 5, 6, 10, and 11 for the required CDRs in the heavy and light chains. Tang et al disclose that the linker must be releasable in the tumor (paragraph [0003]) which meets the limitation of claim 2 for a cleavable linker. Tang et al disclose that the drug of the conjugate is an anti-cancer drug (paragraph [0012]);.a tubulin inhibitor, a DNA damaging agent, or a DNA topoisomerase inhibitor (paragraph [0013]); dolastatin, auristatins and maytansinoids (paragraph [0014]); MMAE (monomethyl auristatin E), MMAF (monomethyl auristatin F), or AF (auristatin F) (paragraph [0015]; calicheamicin, a duocarmycin, or the anthramycin derivative PBD (pyrrolobenzodiazepine) (paragraph [0016]); DNA topoisomerase inhibitor, irinotecan, irinotecan hydrochloride, camptothecin, 9-aminocamptothecin, 9-nitrocamptothecin, 10-hydroxycamptothecin, 9-chloro-10-hydroxycamptothecin, the camptothecin derivative SN-38, 22-hydroxyacuminatine, topotecan, lurtotecan, belotecan, exatecan, an exatecan derivative, homosilatecan, 6,8-dibromo-2-methyl-3-[2-(D-xylopyranosylamino)phenyl]-4(3H)-quinazolinone, 2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-(2E)-2-propenamide, 2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-hydroxyphenylpropyl)-(E)-2-propenamide, 12-β-D-glucopyranosyl-12,13-dihydro-2,10-dihydroxy-6-[[2-hydroxy-1-(hydroxymethyl)ethyl]amino]-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5, 7(6H)-dione, N-[2-(dimethylamino)ethyl]-4-acridinecarboxamide dihydrochloride, or N-[2-(dimethylamino)ethyl]-4-acridinecarboxamide (paragraph [0017]); camptothecin, 10-hydroxycamptothecin, topotecan, belotecan, irinotecan, 22-hydroxyacuminatine, or exatecan (paragraph [0018]), which meets those limitations of claims 3-8, 10, 11, 12, 14, 15, 16-18. Tang et al disclose that the drug can also be a cell differentiation factor, a stem cell trophic factor, a steroid drug, a drug for treating autoimmune disease, an anti-inflammatory drug or a drug for treating infectious disease (paragraph [0006]) which also meets the limitations of claims 3-8, 10, 11, 12, 14, 15, 16-18. Tang et al disclose that the drug has an amino group or an amino group substituted with one alkyl group and links to FF through an amide bond (paragraph [0020]). Tang et al disclose
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which meets the limitations of claims 19 and 20. Tang et al disclose and embodiment wherein each FF is independently:
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(paragraph [0074]) which meets the limitations of claim 21.
Tang et al disclose a drug-conjugate of formula I,
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61
225
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wherein M is
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84
140
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425
269
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358
269
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Tang et al disclose that G is
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67
120
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and n is 4-12 (paragraph [0010]) which meets that limitation in claims 4 and 5.
Tang et al disclose
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515
279
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which meet the structural limitations of claims 3-5, 7, 8, 9, 10, 11, 12, 14, 15, 16, 17
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767
291
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which meet the same limitations in claims 4, 5,
Tang et al disclose
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757
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584
275
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(paragraph [0074]) which meets the limitations of claim 21.
Tang et al disclose the structure of Formula I-1 (paragraph [0088], and Formulas I-2 and I-2-1 (paragraph [0153]); formula I-3 (paragraph [0220]), formula I-4 and formula I-4-1 (paragraph [0225]); formula I-5, formula I-5-1, formula I-6, I-6-1, I-7, I-7-1, I-8, I-8-1, I-9, I-9, I-9-1, I-10, I-10-1, I-11 and I-11-1 (paragraph [0285]), which meet those limitations in claims 6, 9., and 18
Tang et al disclose pharmaceutical composition comprising the drug conjugate, such as the antibody-drug conjugate, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier, an excipient and/or an adjuvant, and optionally other anti-cancer drugs (paragraph [0754]) which meets the limitations of claim 12.. Tang et al disclose a product comprising a drug conjugate or a pharmaceutical composition; a container; and a package insert, instruction or label indicating that the compound or composition is for treating cancer, autoimmune diseases, inflammatory diseases, or infectious diseases. (paragraphs [0769]-[0770]) which meet the limitations of claim 17..
Tang et al disclose the administration of the antibody-drug conjugates for the treatment cancer, autoimmune diseases, inflammatory diseases or infectious diseases; the cancer includes triple-negative breast cancer, glioblastoma, medulloblastoma, urothelial cancer, breast cancer, head and neck cancer, renal cancer (clear cell renal cell carcinoma and papillary renal cell carcinoma), ovarian cancer (e.g., ovarian adenocarcinoma and ovarian teratocarcinoma), pancreatic cancer, gastric cancer, Kaposi's sarcoma, lung cancer (e.g., small cell lung cancer and non-small cell lung cancer), cervical cancer, colorectal cancer, esophageal cancer, oral squamous cell carcinoma, prostate cancer, thyroid cancer, bladder cancer, glioma, hepatobiliary cancer, colorectal cancer, T-cell lymphoma, uterine cancer, liver cancer, endometrial cancer, salivary gland carcinoma, esophageal cancer, melanoma, neuroblastoma, sarcoma (e.g., synovial sarcoma or carcinosarcoma), colon cancer, rectal cancer, colorectal cancer, leukemia (e.g., acute lymphocytic leukemia, acute myelocytic leukemia, acute promyelocytic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), bone cancer, skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma), pancreatic cancer, malignant melanoma, small intestine cancer, testicular embryonal carcinoma, placental choriocarcinoma, testicular cancer, lymphoma (e.g., Hodgkin's lymphoma, non-Hodgkin's lymphoma, or recurrent anaplastic large cell lymphoma) (paragraph [0767]) which meets the limitations of claims 14 and 15. Tang e al disclose that a suitable dose may range from about 0.1 mg/kg to 100 mg/kg, and administration may be performed at a frequency of, for example, once monthly, once every two weeks, once every three weeks, twice every three weeks, three times every four weeks, once weekly, or twice weekly, or that the administration may be performed by intravenous infusion, intravenous bolus injection, subcutaneous injection, intramuscular injection, etc. (paragraph [0767]) which meets the limitations of claims 16.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4, 7, 8, 12, 14, 15, 18-20 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 (1-10, 22-24, 26-31, 33 and 34) of copending Application No. 18/566,271(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the application anticipate the instant claims.
Claim 10 of ‘271 meets the limitations of the B7H3 antibody of the conjugates of instant claim 4. Claim 1 of ‘371 anticipates the chemical structure of instant claim 4. Claim 3 of ‘371 mees the limitation if instant claim 18 to the extent that the antibody of the conjugate is an anti-B7H3 antibody. Claim 29 teach that the drugs of the conjugates of claims 1-6 are MMAE, MMAF, AF, calicheamicin, duocarmycin, anthramycin derivative PBD (pyrrolobenzodiazepine), irinotecan, irinotecan hydrochloride, camptothecin, 9-aminocamptothecin, 9-nitrocamptothecin, 10-hydroxycamptothecin, 9-chloro-10-hydroxycamptothecin, the camptothecin derivative SN-38, 22-hydroxyacuminatine, topotecan, lurtotecan, belotecan, exatecan, homosilatecan, 6,8-dibromo-2-methyl-3-[2-(D-xylopyranosylamino)phenyl]-4(3H)-quinazolinone, 2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-(2E)-2-propenamide, 2-cyano-3-(3,4-dihydroxyphenyl)-N-(3-hydroxyphenylpropyl)-(E)-2-propenamide, 12-β-D-glucopyranosyl-12,13-dihydro-2,10-dihydroxy-6-[[2-hydroxy-1-(hydroxymethyl)ethyl]amino]-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione, N-[2-(dimethylamino)ethyl]-4-acridinecarboxamide dihydrochloride, N-[2-(dimethylamino)ethyl]-4-acridinecarboxamide, or a pharmaceutically acceptable salts or solvates thereof which meet that limitation of instant claim 4. Claim 30 meets the limitations of instant claim 7 to the extent that the antibody of the conjugate is an anti-B7H3 antibody. Claim 31 meets the limitations of instant claim 8 to the extent that the antibody of the conjugate is an anti-B7H3 antibody. Claims 22 and 23 meet the limitations of instant claims 19 and 20 to the extent that the antibody of the conjugate is an anti-B7H3 antibody. Claim 33 meets the limitations of instant claim 12 to the extent that the antibody of the conjugate is an anti-B7H3 antibody. Claim 26 meets the limitations of instant claims 14 and 15 to the extent that the antibody of the conjugate is an anti-B7H3 antibody
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
Prosecution Insights