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 .
DETAILED ACTION
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 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.
Response to Restriction/Election
Applicant’s election of without traverse of “GAM-PEG4-CCH” for “modified binding moiety”, “GAR-PEG8-SS-HA-N3” for “first modified binding molecule” and “GAM-PEG4-CCH” for “second modified binding molecule”, in response to election of species requirement is acknowledged. Claims 3, 5, 8, 10, 12 and 20 do not read on the elected species.
Therefore, claims 3, 5, 8, 10, 12 and 20 are withdrawn from further consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Applicants preserve their right to file a divisional on the non-elected subject matter.
Status of the claims
Claims 1-2, 4, 6-7, 9, 11 and 13-19 are examined on merits in this office action.
Claim Rejections - 35 USC § 112
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 1-2, 4, 6-7, 9, 11 and 13-19 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.
Claims 1-2, 4, 6-7, 9 and 11 are directed to a modified binding moiety comprising a non-cleavable bridge component and a specific binding moiety wherein the non-cleavable bridge component comprising a non-cleavable linker and a chemical ligation group wherein the chemical ligation group is at a terminus of the non-cleavable linker and non-cleavable bridge component is bonded to the the specific binding moiety through the non-cleavable linker.
The non-cleavable linker has not been clearly defined in the specification and thus the linker composition encompasses an inordinately a large number of distinct structures for which the specification does not have a clear descriptive support. Non-cleavable is a vague term and the cleavage of a linker depends on various condition. When a linker is cleavable by acid, may not be cleavable by an enzyme or other condition. A enzyme cleavable linker may be considered non-cleavable by other conditions. Therefore, without defining the cleavage condition, non-cleavable linker encompasses an inordinately a large number of distinct structures having distinct properties. The chemical ligation group of modified binding moiety encompasses a large number of structurally and functionally distinct groups. As for example, the chemical ligation group encompasses among others, azide, thioester, alkyne, a halogen , a tyramide, quinone methide precursor and each are structurally and functional distinct. Moreover, each encompasses various structures. Moreover, the linkages may encompass various types of bondings including covalent, non-covalent, electrostatic and so on. Therefore, the combination, permutation and various various distinct compounds encompassed by each of “cleavage site”, “chemical ligation group” and “non-cleavable linker” provides an inordinately a large number of structurally and functionally divergent species of compounds within the genus of first modified binding moiety for which the specification does not have a clear descriptive support. Throughout the specification, only disclosure for non-cleavable linker is cited in page 39 which discloses a linker for conjugating with an antibody and which is
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. The only disclosure of ethylene oxide containing linker having terminal alkyne for non-cleavable linker cannot be considered as a representative of the vast number of linkers as described above encompassed by various types of linkers (see claims 10 and 11) and various types of linkages as encompassed by the claims. The only a few species disclosed in the specification cannot possibly typify the entire genus claimed or account for the variation between species of such a large genus.
Claims 13-19 are directed to a kit composition comprising a first modified binding molecule and a second modified binding molecule, wherein the first modified binding moiety comprises at least one a cleavable bridge component and a first binding moiety, wherein the cleavable bridge component comprises a cleavage site, a detectable moiety, and a first chemical ligation group and the second modified binding molecule, wherein the second modified binding molecule comprising a non-cleavable bridge component as claimed in claim 1.
The second modified binding molecule of the kit composition lacks descriptive support for representative species for the same reason as discussed above for claims 1-2, 4, 6-7, 9 and 11.
The kit composition also comprises first modified binding molecule, which also encompass a large number structurally distinct compounds encompassed by the combination of a “cleavable bridge component” and “a first antibody” wherein the “cleavable bridge component” comprises various combinations and permutation of a “cleavage site”, “detectable moiety” and a “first chemical ligation group”. The linkage of the antibody and arrangement of the antibody with respect to the components of the cleavable bridge components have not been clearly defined in the claim and thus the claim encompass non-covalent linkage through antibody-antigen (antibody-epitope binding) type specific binding to the cleavage site of the cleavable bridge component to provide a structure wherein the cleavage site is more proximal to the antibody than is the detectable moiety and the first chemical ligation group. Claim 18 recites various groups for each of the cleavage site, detectable moiety and chemical ligation group but however, does not mention as to whether they are in a conjugated structure (linked structure) and thus various un-linked state and various noncovalent association including electrostatic, hydrophobic and electrostatic linkages as encompassed among the various recited groups. The cleavage site encompasses various structurally distinct groups. Throughout the specification, the only example and description for diols is strictly limited to vicinal diol capable of being cleaved by NaIO4 (para [0158]). The term “nitrophenyl derivative” has not clearly been described in the specification and thus encompasses various types of derivatized structures derived from nitorphenyl by various reactions (addition, substitution, deletion). However, throughout the specification, the only description for nitrophenyl derivative is directed to nitrophenyl derivative capable of being cleaved by untraviolet irradiation (paragraph [0158]) without providing a clear structure of a nitrophenyl derivative.
Therefore, the combination, permutation and various orientation of various distinct compounds encompassed by each of “cleavage site”, “detectable moiety”, “first chemical ligation group” and “first binding molecule” and the combination, permutation, and various orientation of various distinct compounds encompassed by “second modified binding molecule” and “modified binding moiety of claim 1” provide an inordinately a large number of structurally and functionally divergent species of compounds within the genus of first modified binding molecule, within the genus of a modified binding moiety and within the genus of second modified binding molecule, for which the specification does not have a clear descriptive support. The only a few species disclosed in the specification cannot possibly typify the entire genus claimed or account for the variation between species of such a large genus.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), the Federal Circuit noted the importance of an application's disclosure and stated, “the hallmark of written description is disclosure.” A disclosure adequately describes an invention when it “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Id. at 1351. “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011). The case of In re Ruschig (379 F.2d 990, 154 USPQ 118 (CCPA 1967)) makes clear that one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say “here is my invention.” In order to satisfy the written description requirement, the blaze marks directing the skilled artisan to that tree must be in the originally filed disclosure. See id. at 994-95, 154 USPQ at 122; Fujikawa, 93 F.3d at 1570-71, 39 USPQ2d at 1905; Martin v. Mayer, 823 F.2d 500, 505, 3 USPQ2d 1333, 1337 (Fed. Cir. 1987) (“It is 'not a question of whether one skilled in the art might be able to construct the patentee's device from the teachings of the disclosure .... Rather, it is a question whether the application necessarily discloses that particular device.'”) (quoting Jepson v. Coleman, 314 F.2d 533,536, 136 USPQ 647, 649-50 (CCPA 1963)). A written description of a chemical genus “requires a precise definition, such as by structure, formula, [or] chemical name” of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997). The Federal Circuit reflected on Eli Lilly in Ariad while explaining how to sufficiently describe of a genus of compounds: We held that a sufficient description of a genus instead 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. Id. at 1568-69. We explained that an adequate written description requires 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. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). Merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. A "representative number of species" must typify the entire claimed genus and account for variation between the species of the genus. When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A description of what a material does, rather than of what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. [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. Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004).
However, throughout the specification, the disclosure of a species of cleavable bridge component comprising the cleavage site, detectable moiety and the first chemical ligation group is very limited to hemagglutinin (HA) linked to azide through an ethylene oxide repeat (HA-azide) (
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) and wherein the HA azide is linked at the terminal cysteine of HA to dithiol linker of formula (III)
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and the only species disclosed for a completed structure for first modified binding moiety in the specification is disclosed in fig.7:
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.
The disclosure of only a few species of a compound and the process of providing one or two species of a compound, while the compounds as described above encompass an inordinately a large number of structurally divergent species of substantial variance, cannot be considered representative disclosure or representative of various distinct species and the various reaction conditions for providing the distinct species of compound. The only a few species disclosed in the specification cannot possibly typify the entire genus claimed or account for the variation between species of such a large genus when there is substantial variation within the genus as described above.
The disclosure of only a limited number of species representing “first modified binding molecule”, “second binding molecule” and “modified binding moiety” and disclosure of very limited reaction condition for providing limited species are not representative of the enormous number of various distinct species that are encompassed by the genus of “first modified binding molecule”, “second binding molecule” and “modified binding moiety”, provided by the various permutation, combination and orientation of the various distinct structures encompassed by of each the “non-cleavable bridge component”, “cleavable bridge component” and “specific binding moiety”,.
Claim Rejections - 35 USC § 102
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.
Claims 1-2, 6-7 and 9 are rejected under 35 U.S.C. 102(a1) as being anticipated by Zimmerman et al. (Bioconjugate Chem. 2014).
In regards to claims 1, Zimmerman disclosed an antibody linker to a linker wherein the linker comprises a terminal azide functionalized group:
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. The above modified antibody (i.e. modified binding moiety) comprises an antibody (i.e. a specific binding moiety) having at least one non-cleavable bridge component wherein the non-cleavable bridge component comprises (i) a non-cleavable linker
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and a chemical ligation group azide (
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), wherein the chemical ligation group is at a terminal of the at least one non-cleavable bridge component, wherein the at least one non-cleavable bridge component is bonded to the antibody (i.e. the specific binding moiety) through the non-cleavable linker.
In regards to claim 2, as disclosed above, the specific binding moiety is an antibody.
In regards to claims 6 and 7, as disclosed above the chemical ligation group is an azide group, which is a reactive functional group.
In regards to claim 9, Zimmerman discloses azide group, which is a biorthogonal reactive group and is stable under physiological conditions.
In regards to claim 17, as described above, Shimoboji teaches that the photoresponsive polymers rely on the cis-trans isomerization of diazobenzene chromophores to trigger the change in physical properties.
In regards to claim 29, Shimoboji discloses biotin ligand for streptavidin and biotin is considered as a biomolecule or a small molecule.
Claims 1, 6, 7, 9 and 11 are rejected under 35 U.S.C. 102(a1) as being anticipated by Pierce Avidin Biotin Catalog (Pierce Biotechnology, 2005).
In regards to claims 1, Pierce catalog disclosed a modified binding moiety having the structures:
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. The modified binding moiety comprises: (a) at least one non-cleavable bridge component
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and
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; and (b) a specific binding moiety biotin, wherein the at least one non-cleavable bridge component as disclosed above, comprises (i) a non-cleavable linker, and (ii) a chemical ligation group (NHS or maleimide group), wherein the chemical ligation group is at a terminal of the at least one non-cleavable bridge component, wherein the at least one non-cleavable bridge component is bonded to the specific binding moiety biotin through the non-cleavable linker.
In regards to claims 6 and 7, the chemical ligation groups NHS and maleimide are both reactive functional group and maleimide comprising alkene group.
In regards to claim 9, the chemical ligation group is stable under physiological conditions.
In regards to claim 11, as disclosed above, the non-cleavable linker comprises polyethylene group.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 4, 6-7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zimmerman et al. (Bioconjugate Chem. 2014).
Zimmerman has been described above anticipating a modified binding moiety comprising a non-cleavable bridge component and a specific binding moiety as claimed in claims 1-2, 6-7 and 9.
Zimmerman discloses that the specific binding moiety is an antibody wherein the antibod. Zimmerman, however, does not teach secondary antibody a specific binding moiety.
However, since Zimmerman teaches specific binding moiety with click reactive group (azide group) for conjugation with compounds having complementary click reactive group (alkyne), one of ordinary skilled in the art can easily envisage various specific binding moiety in place of antibody, including secondary antibody having a click reactive group with the expectation of expanding the arsenal of various specific binding moiety conjugates with various other compounds having complementary click reactive group with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHAFIQUL HAQ whose telephone number is (571)272-6103. The examiner can normally be reached on Mon-Fri 8-4:30.
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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