DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 52-57, 59-71 and 73-75 are pending and under examination.
35 USC § 112(a) rejections withdrawn
The rejection of claims 52-57, 59-71 and 73 for failing to comply with the written description requirement as being drawn to new matter are withdrawn in view of Applicant’s arguments
35 USC § 112(a) rejections maintained
The rejections of claims 52-57, 59-71 and 73-75 under 35 U.S.C. 112(a), as failing to comply with the written description requirement are maintained.
Applicant argues that the rejection for alleged lack of written description appears to be premised on the allegation that the specification only discloses that two known antibodies are capable of binding to the recited discontinuous peptides, but does not disclose the production of antibodies "capable of specifically binding to an epitope or epitope segment of glypican 1 (GPC-1)" using the recited discontinuous peptides of the GPC-1 protein or GPC-1 peptides with substitutions, i.e. by "immunising an animal with a peptide comprising two segments" or "GPC-1 peptides with substitutions". Applicant argues that the pending claims are not directed to immunising an animal with the recited discontinuous peptides of the GPC-1 protein or GPC-1 peptides with substitutions to produce antibodies but rather, the claims of the subject application recite either immunising an animal with GPC-1 or a fragment thereof to generate anti-GPC-1 antibodies or generating a library comprising antibodies and/or antigen binding fragments thereof and then selecting an antibody capable of binding to the recited epitope or epitope segments.
Applicant further argues that new claims 74 and 75 recite immunising an animal with GPC-1. Page 39, lines 22-23 explains that "polyclonal and monoclonal antibody preparations that bind specifically to GPC-1 epitope/s of the present invention can be prepared using known techniques." Moreover, lines 24-26 explain that "[a]ny technique that provides for the production of antibody molecules by continuous cell lines in culture may be used in the preparation of monoclonal antibodies directed toward a target GPC-1 epitope." Page 40, lines 21-24 of the specification further explains that "[f]or the production of polyclonal antibodies against a given combination of GPC-1 epitopes, various host animals can be immunised by injection with the epitopes, including, but not limited to, rabbits, chickens, mice, rats, sheep, goats, etc." Applicant argues that as explained on page 40, lines 32-33 of the specification, "screening for the desired antibody can be accomplished by a variety of techniques known in the art."
Applicant argues that adequate written description of the claimed invention is supported by caselaw that clearly distinguishes between claims directed to methods of using a compound with a particular activity and assays for identifying compounds with
that activity. In Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004 ) , the patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product. While the court held that the inventors were not in possession of such claims because the specification did not disclose any compound with the recited ability to inhibit the expression or activity of the PGHS-2 gene product, they explicitly noted that there was adequate written description for
assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product. Applicant argues that as here, the claims to assays for identifying compounds with a particular activity are adequately described and were in possession of the inventors despite any alleged failure to describe compounds with the
activity.
Applicant arguments have been considered but are not persuasive. Applicant has previously argued that "selecting an antibody capable of specifically binding to the epitope or epitope segment of GPC-1", explicitly contemplates selecting antibodies that specifically bind the epitope or epitope segment of GPC-1. (page 40, lines 10-12 which states that "[h] ybridomas producing a monoclonal antibody capable of binding specifically to a GPC-1 epitope of the present invention are identified by their ability to immunoreact with the epitope/s presented." Thus, selecting an antibody capable of specifically binding to the epitope or epitope segment of GPC-1 requires an antibody that specifically binds to a GPC-1 epitope of the present invention. Thus, the present claims are not just drawn to a screening method as recited in In Univ. of Rochester but methods for selecting and identifying. It has bee interpreted that methods for isolating, separating the antibody from the GPC-1 epitope and selecting an antibody would require knowledge of the amino acid structure of that antibody or disclosure of sufficiently detailed, relevant identifying characteristics ....i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. It is noted that the present claims encompass monoclonal antibodies to the listed fusion peptides.
The specification discloses the construction of discontinuous epitopes to develop a library of both continuous and discontinuous peptides The specification discloses that the MIL38 antibody appears to bind a discontinuous epitope consisting of SEQ ID NO. 2 and SEQ ID NO. 7. Polyclonal rabbit anti-GPC1 antibody 137604 bound to a peptide consisting of SEQ ID NOS: 2, 10 and 11 (Section 2.2). Mouse monoclonal antibody bound to the peptide of SEQ ID NO:13 (Id). Polyclonal goat anti-GPC-1 (GPC1) bound to a fusion peptide consisting of SEQ ID NOS: 2 and 9) (Id). However, the specification does not disclose the production of any antibodies using discontinuous peptides of the GPC-1 protein. In addition, the specification only disclose two monoclonal antibodies that bound to GPC1 peptides, and both those antibodies are already known. Thus, the specification does not disclose the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies. As previously discussed, the present claims encompass monoclonal antibodies to the listed fusion peptides.
In this case, the specification does not appear to describe disclose the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies comprising immunizing an animal with a peptide comprising two segments and thus does not satisfy either the Lilly nor Enzo standards. The specification does not disclose the production of any monoclonal antibodies using discontinuous peptides of the GPC-1 protein. Furthermore, the specification does not disclose the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies using GPC-1 peptides with substitutions. The specification only disclose that two known monoclonal antibodies were capable of binding discontinuous peptides, but not the discontinuous peptides were capable of producing any antibodies in vivo. It is noted that many of the claimed peptides comprising two segments would not comprise the amino acid sequence of the GPC-1 full length protein.
The rejections of claims 52-57, 59-71 and 73-75 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement are maintained. 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.
Applicant argues that the rejections for alleged lack of enablement appears to be premised on the allegation that the specification does not disclose "the production of any antibodies using discontinuous peptides of the GPC- 1 protein" or "using GPC-1 peptides with substitutions". Applicant argues that as discussed above with respect to the written description rejection, the pending claims are not directed to immunizing an animal with the recited discontinuous peptides of the GPC-1 protein or GPC-1 peptides with substitutions to produce antibodies but rather, the claims of the subject application recite generating antibodies or binding entities, for example by immunizing an animal with GPC-1 or a fragment thereof to generate anti-GPC-1 antibodies, and then selecting an antibody capable of binding to the recited epitope or epitope segments.
Applicant also argue that new claims 74 and 75 recite immunising an animal with GPC-1. Applicant argues that as noted above, processes for producing antibodies, for example by immunizing an animal with an antigen, were well-known at the time of
the invention. Applicant argues that methods of screening for antibodies with the
desired binding activity were well-known at the time of the invention and the specification in fact provides an example of such screening.
Applicant’s arguments have been considered but are not persuasive. The specification does not disclose the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies using discontinuous peptides of the GPC-1 protein, as required by the present claims. Furthermore, the specification does not disclose the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies using GPC-1 peptides with substitutions. It has been interpreted that the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies would require that the GPC-1 fusion peptides were immunogenic. However, as disclosed by Wang and by Celis the vast majority of peptides would not induce an immune response. It is generally thought that approximately 10% of peptides are capable of inducing an immune response. Wang discloses that the structure a T cell epitope that stimulates immune response in context of MHC molecules is unpredictable. Celis teach that in order to establish whether a peptide is immunogenic said peptide needs to be tested in assays that actually establish that a peptide is immunogenic. Celis et al further teach that “In addition to MHC binding, other factors such as antigen processing, peptide transport and the composition of the T-cell receptor repertoire could determine whether any of these peptides can function to induce an immune response.
Thus, determining whether a particular peptide is capable of producing an antibody is not straightforward.
MPEP 2164.08(b) states that
The presence of inoperative embodiments within the scope of a claim does not necessarily render a claim nonenabled. The standard is whether a skilled person could determine which embodiments that were conceived, but not yet made, would be inoperative or operative with expenditure of no more effort than is normally required in the art. Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984) (prophetic examples do not make the disclosure nonenabling).
Although, typically, inoperative embodiments are excluded by language in a claim (e.g., preamble), the scope of the claim may still not be enabled where undue experimentation is involved in determining those embodiments that are operable. A disclosure of a large number of operable embodiments and the identification of a single inoperative embodiment did not render a claim broader than the enabled scope because undue experimentation was not involved in determining those embodiments that were operable. In re Angstadt, 537 F.2d 498, 502-503, 190 USPQ 214, 218 (CCPA 1976). However, claims reading on significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.
The present claims lists an extremely large number of peptides and does not disclose which of these extremely large number of peptides would be capable of inducing an immune response allowing the isolation, separation of the antibody from the GPC-1 epitope and selection any monoclonal antibodies using discontinuous peptides of the GPC-1 protein. As MPEP 2164.08(b) recites, claims reading on significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Given that the majority of the listed peptides in the present claims would likely not be immunogenic and given that the present claims list an extremely large number of peptides, it would require undue experimentation in determining which ones of those extremely large number of peptides are operative.
Given the disclosure of the specification that did not disclose how to isolate, separate an antibody from the GPC-1 epitope and select any monoclonal antibodies through the isolation, separation of the antibody from the GPC-1 epitope and selection GPC-1 peptide comprising two segments, the claims encompassing peptides having multiple substitutions to the GPC-1 peptides and the teaching in the art concerning the unpredictability of producing antibodies to peptides, one skilled in the art could not predictably produce and isolate antibodies to peptides comprising two segments, especially peptides having substitutions to the GPC-1 peptides.
Therefore, in view of the breadth of the claims, lack of guidance in the specification, the absence of working examples, and the state of the art, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
In response to Applicant’s argument that the pending claims are not directed to immunizing an animal with the recited discontinuous peptides of the GPC-1 protein or GPC-1 peptides with substitutions to produce antibodies but rather, the claims of the subject application recite generating antibodies or binding entities, for example by immunizing an animal with GPC-1 or a fragment thereof to generate anti-GPC-1 antibodies, the specification does not disclose any generated anti-GPC-1 antibodies through the immunization an animal with GPC-1 or a fragment. As previously discussed, It would require undue experimentation to determine which GPC-1 or a fragment thereof would be capable of generating anti-GPC-1 antibodies.
Summary
Claims 52-57, 59-71 and 73-75 stand rejected
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/MARK HALVORSON/ Primary Examiner, Art Unit 1646