Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Status of the Claims
1. Claims 1-27 are the original claims filed 4/9/2024. In the preliminary amendment of 7/12/2024, claims 21-27 are canceled.
Claims 1-20 are all the claims.
Priority
2. USAN 18/630,602, filed 04/09/2024, is a Continuation of 17/376,627, filed 07/15/2021, now abandoned, 17/376,627 is a Continuation of 16/181,054, filed 11/05/2018, now abandoned, 16/181,054 is a Divisional of 15/274,989, filed 09/23/2016, now abandoned, 15/274,989 is a Divisional of 14/181,334, filed 02/14/2014, now U.S. Patent # 9487588 and having 1 RCE-type filing therein,
14/181,334 is a Continuation of 12/545,279, filed 08/21/2009, now U.S. Patent # 8691225 and having 1 RCE-type filing therein, 12/545,279 is a Continuation in Part of 12/425,874, filed 04/17/2009, now abandoned, 12/425,874 is a Continuation in Part of 12/281,925, filed 09/05/2008, now U.S. Patent # 7846440, 12/281,925 is a National Stage entry of PCT/US2008/002119, International Filing Date: 02/15/2008,
PCT/US2008/002119 Claims Priority from Provisional Application 60/901,904, filed 02/16/2007, PCT/US2008/002119 Claims Priority from Provisional Application 61/009,796, filed 01/02/2008.
Information Disclosure Statement
3. As of 9/4/2026, no IDS is filed for this application.
Objections
Drawings
4. The drawing sheets for Figures 1A, 6A-6D,19B, and 34A-34E are objected to because of the improper use of the term Alexa (Fig. 1A, 6A-6D, 34A-34E) and Erbitux (Fig. 19B), which is a trade name or a mark used in commerce, have been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
5. The abstract of the disclosure is objected to because it contains the term “novel” for the description of the invention. Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
6. The disclosure is objected to because of the following informalities:
a) The use of the term, i.e., Sepharose, Biacore, Tween, Triton, Tris, Erbitux, Metamorph Analysis, FACSCalibur, SuperSignal, DuoSet, NUNC MaxiSorb, Eppendorf tubes, M-PER, ATCC, Xenomouse, Gemzar, Nolvadex, Trexall, Tyverb, GenBank, nanobody, Alexa, SUPERSIGNAL, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
b) The specification contains a peptide sequence > 4 amino acids in length that pursuant to 37 CFR 1.821-1.825 is required to be identified by sequence identifier, i.e.,
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Appropriate correction is required.
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.
7. Claims 7-14, 17 and 20 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) Claims 7-14 and 17 are unclear for the phrase “a subject” without distinguishing that the subject has a cancer (implied therapy) or is predisposed to having a cancer (implied prophylaxis). See the specification at
[0147] The terms “treat,” “treating,” and “treatment,” as used herein, refer to therapeutic or preventative measures described herein. The methods of “treatment” employ administration to a subject, an antibody or antigen binding portion disclosed herein, for example, a subject having a disease or disorder associated with ErbB3 dependent signaling or predisposed to having such a disease or disorder, in order to prevent, cure, delay, reduce the severity of, or ameliorate one or more symptoms of the disease or disorder or recurring disease or disorder, or in order to prolong the survival of a subject beyond that expected in the absence of such treatment.
b) Claim 20 contains the trademark/trade name affibody.
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Claim 20 contains the trademark/trade name nanobody.
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Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name.
In the present case, the trademark/trade name for “nanobody” is used to identify/describe single-domain antibody or VHH and, accordingly, the identification/description is indefinite.
In the present case, the trademark/trade name for “affibody” is used to identify/describe a small (6.5-kDa) affinity protein based on a three-helix bundle domain framework and, accordingly, the identification/description is indefinite.
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.
Written Description
8. Claims 15-17 and 19-20 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.
Claim interpretation/construction
Claim 15-16 and 19-20 drawn to a generic monoclonal antibody or fragments thereof that bind anywhere within the range of residues 92-104 and 129 corresponding to an ErbB3 epitope for the sequence of SEQ ID NO: 73 and compositions (claims 15-16), a human, humanized, bispecific or chimeric antibody thereof (claim 19), and antibody fragments inclusive of a single variable domain, e.g., SMIP, affibody, nanobody and domain antibody (claim 20).
Claim 17 is drawn to a method of treating (therapeutic/prophylactic) any cancer in a subject each comprising the genus of antibodies of Claim 15.
Definitions
“Epitope” (Claim 15): as defined in the specification is a generic meaning or the epitope is located in the ectodomain of ErbB3 as follows:
[0118] The term “epitope” or “antigenic determinant” refers to a site on an antigen to which an immunoglobulin or antibody specifically binds. Epitopes can be formed both from contiguous amino acids or noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained on exposure to denaturing solvents, whereas epitopes formed by tertiary folding are typically lost on treatment with denaturing solvents. An epitope typically includes at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acids in a unique spatial conformation. Methods of determining spatial conformation of epitopes include techniques in the art and those described herein, for example, x-ray crystallography and 2-dimensional nuclear magnetic resonance. See, e.g., Epitope Mapping Protocols in Methods in Molecular Biology, Vol. 66, G. E. Morris, Ed. (1996).
[0007] …(vii) binding to an epitope located on ectodomain (extracellular domain) Domain I, which corresponds to amino acid residues 1 to about 190 of mature ErbB3 (SEQ ID NO: 73), for example, an epitope involving or spanning any portion of residues 1-183 of SEQ ID NO: 73, more preferably involving or spanning residues 93-104 or 92-129 of SEQ ID NO: 73, even more preferably involving residues 92, 93, 99, 101, 102, 104 and 129 of SEQ ID NO: 73 or residues 93, 101, 102, and 104 of SEQ ID NO: 73.
[0017] Also encompassed by the present invention are antibodies and antigen binding portions thereof that bind to the same or overlapping epitopes bound by any of the antibodies or portions thereof described herein (e.g., an epitope located on Domain I of the ectodomain of ErbB3), such as an epitope involving or spanning any of residues 1-183 of the amino acid sequence of mature ErbB3 (SEQ ID NO: 73), more preferably involving or spanning residues 93-104 or 92-129 of SEQ ID NO: 73, even more preferably involving residues 92, 93, 99, 101, 102, 104 and 129 of SEQ ID NO: 73 or residues 93, 101, 102, and 104 of SEQ ID NO: 73. Antibodies which have the same epitope binding activity as the antibodies described herein, e.g., antibodies having the same sequence as Ab #6 or binding epitopes involving residues 93-104 of SEQ ID NO: 73, are also encompassed by the present invention.
“treat/treating” (Claim 17): the specification is explicit in the meaning covering both therapeutic and preventative/prophylactic outcomes at
[0148] The terms “treat,” “treating,” and “treatment,” as used herein, refer to therapeutic or preventative measures described herein. The methods of “treatment” employ administration to a subject, an antibody or antigen binding portion disclosed herein, for example, a subject having a disease or disorder associated with ErbB3 dependent signaling or predisposed to having such a disease or disorder, in order to prevent, cure, delay, reduce the severity of, or ameliorate one or more symptoms of the disease or disorder or recurring disease or disorder, or in order to prolong the survival of a subject beyond that expected in the absence of such treatment.
“subject” (Claim 17): is defined in the specification as a subject receiving a therapeutic or prophylactic treatment at
[0154] The term “patient” includes human and other mammalian subjects that receive either prophylactic or therapeutic treatment.
Because applicants seek patent protection for all such anti-ErbB3 antibodies having a proscribed epitope binding activity in addition to the therapeutic/prophylactic functional attributes defined in the method claim, this genus must be adequately described. A description adequate to satisfy 35 U.S.C. § 112(a) must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed (Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). The purpose of the written description requirement is to “ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent’s specification” (In re Katz Interactive Call Processing Patent Litig. 639 F.3d 1303, 1319 (Fed. Cir 2011).
Scope of the claimed genus
The claims encompass anti-ErbB3 antibodies, and variations to the VH and VL domains, or a single variable domain including the complementarity determining regions (CDRs) that vary relative to the VLC and VHC and CDRs found in any parental antibody. The claims encompass single domain antibodies and fragments thereof. The genus encompassed by the claims is therefore very large and there is substantial variation within the genus.
State of the Relevant Art
By the time the invention was made, it was also well-established in the art that the formation of an intact antigen-binding surface on an antibody required the association of the complete heavy and light chain variable regions, 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 (Almagro & Franssen, Frontiers in Bioscience, 13:1619-33 (2008) (PTO-892) (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). While this overall architecture is shared among antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level, even when the same antigen is bound (Edwards et al., J Mol Biol 334:103-118 (2003) (PTO-892); see also Marchalonis et al., Dev & Comp Immunol. 30:223-247 (2006) (PTO-892), summarized in Abstract and Conclusion.
Methods of preparing antibodies from a variety of species to a protein or peptide of interest were well-established in the art at the time the invention was made. But application of those methods to any given antibody was still a matter of trial-and-error testing, and the skilled person could not automatically predict which residues in the CDRs would be tolerant of mutations, or which amino acid substitutions would maintain antigen binding. Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. For example, it is generally the case that absent the fundamental structure provided for by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, a person of ordinary skill cannot visualize or otherwise predict what an antibody with a particular set of functional properties would look like structurally.
Moreover, the state of the art acknowledged that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function. Moreover, the state of the acknowledged that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function. Lippow, for example, teaches that a single point mutation in the CDR of a parent antibody led to as much as an eightfold improvement in binding affinity in the resulting mutant (p. 1172, left col., lines 7-8 from end of first full paragraph and Table 1a) (Lippow et al., “Computational design of antibody-affinity improvement beyond in vivo maturation,” Nature Biotechnology, 25(10):1171-1176 (2007) (PTO-892).
Sulea teaches that individual point mutations gave an improvement of one order of magnitude in binding affinity, which in turn, generated a 6-fold enhancement of efficacy at the cellular level (Abstract) (Sulea et al., “Application of Assisted Design of Antibody and Protein Therapeutics (ADAPT) improves efficacy of a Clostridium difficile toxin A single-domain antibody," Scientific Reports, 8(260):1-11 (2018) (PTO-892). Hasegawa et al. reports that a single amino acid substitution in the variable region was sufficient to alter the efficiency of biosynthesis and the variant antibody acquired stronger binding affinity to its antigen than the parent (Hasegawa et al., “Single amino acid substitution in LC-CDR1 induces Russell body phenotype that attenuates cellular protein synthesis through elF2a phosphorylation and thereby downregulates IgG secretion despite operational secretory pathway traffic,” MABS, VOL. 9, NO. 5, pp. 854-873 (2017) (PTO-892)). Altshuler teaches that generally, “CDR mutations should not involve residues that can play structural functions (form parts of the domain ‘internal core’, internal salt bridges, hydrogen bonds, etc.).” “Usually these are conservative residues, and any substitution of these residues causes decrease[s] in affinity” (Altshuler et al., “Generation of Recombinant Antibodies and Means for Increasing Their Affinity,” Biochemistry (Moscow), 75(13):1584-1605 (2010) at p. 1600, col. 1, para. 2, lines 1-5 (PTO-892).
Accordingly, a person of ordinary skill in the art would have recognized that it was highly unpredictable that any single domain VH or single domain VL much less fragments thereof (containing less than of the CDRs or FRs) could be modified to create an unlimited claimed antibody, without increasing, eliminating, or in some way altering antigen binding.
Summary of species disclosed in the specification
AS regards the minimum essential function for the genus of antibodies falling within the scope of generic Claim 15, whilst Applicant’s specification fully discloses the human anti-ErbB3 antibodies referred to as Ab #6, Ab #3, Ab #14, Ab #17, and Ab #19, it is only Ab #6 shown to meet the claimed required criteria. The clones are further derived and the prototype ab #6 assayed for epitope mapping in Examples 4 and 18. Note also the ab#6 comprises the full VH and full VL domains and nothing less for the epitope mapping criteria:
Example 4 for Ab #6:
[0285] A DNA fragment encoding an ErbB3 ectodomain fragment corresponding to amino acid residues 1-183 of mature ErbB3 (SEQ ID NO: 73) is cloned into the yeast display vector pYD2 (a modified version of pYD1 (Invitrogen) with a stop codon engineered in front of the His tag) between the Nhe and BsiWI restriction sites. The plasmid is transformed into the yeast strain EBY100 (Invitrogen) and clones containing the plasmid selected on Trp-selective medium. The clone is grown in glucose containing medium overnight at 30° C. and expression of the ErbB3 truncation mutant is induced by transfer to a galactose-containing medium for 2 days at 18° C. Yeast displaying the ErbB3 truncation mutant are stained with 50 nM of Ab #6, followed by a goat anti-human antibody labeled with Alexa dye-647. A separate sample is stained with the goat anti-human antibody only to show that there is no non-specific binding to yeast of the secondary antibody. Analysis is performed by flow cytometry on the FACSCALIBUR cell sorter (BD Biosciences).
[0286] As shown by the data (obtained using the methods described above or minor variations thereof) presented in FIG. 39, Ab #6 bound to the ErbB3 ectodomain, i.e., amino acid residues 1-183 of mature ErbB3 (SEQ ID NO: 73).
Example 18 for Ab #6:
[0384] the Ab #6 epitope comprises residues 93, 101, 102 and 104 of mature ErbB3 (SEQ ID NO: 73),
[0385] Thus, full-length ErbB3 CHO cell expression experiments demonstrate that the Ab #6 epitope on ErbB3 comprises residues 93, 101, 102 and 104 of the mature, human ErbB3 sequence shown in SEQ ID NO: 73. These four residue are located on strand 3 of a 5 stand parallel beta-sheet within ErbB3. Further experiments performed in analogous fashion yielded data indicating that the epitope further comprises residues 92, 99 and 129 of the mature, human ErbB3 sequence shown in SEQ ID NO: 73. Thus, the epitope bound by Ab #6 may be viewed as comprising the sequence spanning residues 92-104 and 129 (which lies adjacent to 92-104 in the folded protein), of the mature, human ErbB3 sequence shown in SEQ ID NO: 73.
Are the disclosed species representative of the claimed genus?
It is asserted that the disclosed species are not representative of the claimed genus because the claims encompass known-and-yet to be discovered anti-ErbB3 antibodies and defined only by the epitope range to which they bind of the sequence of SEQ ID NO: 73. The extent of antibody variation would be structurally distinct but unpredictable whether the structure/function correlation was met for generic Claim 15 much less all of the dependent claims, i.e., being treatment effective (Claim 17) for therapy and prophylaxis. The specification does not identify which VH or VL domains, which combination of fewer than all six CDRs, or which subset of residues in the combination of CDRs is essential for the recited function of binding the epitope of the sequence of SEQ ID NO: 73. Neither the specification nor the prior art provides guidance as to what structural changes can be made to the parent sequences and still predictably arrive at an antibody that binds ErbB3. The single disclosed species therefore does not represent the claimed genus.
Has Applicant provided a common structure sufficient to visualize the genus?
It is not disclosed in the specification nor the prior art as to what the common and canonical structural features are for a generic anti-ErbB3 antibody in order to maintain binding with the claimed range of residues for the epitope of ErbB3 protein claimed in Claim 15 much less the additional functional attributes required of the genus of antibodies for Claims 17 (therapeutic or prophylactic), or 19 (humanized). Even in 2021, several years after the effective filing date of the claimed invention, antibodies are still not understood well enough to allow researchers to predict with certainty what modifications can be made to a primary antibody sequence such that binding is maintained. “[T]he major test of understanding is whether the changes associated with antibody maturation can be predicted with any reasonable accuracy, and whether there is sufficient information for developing therapeutic antibodies,” Vajda et al., “Progress toward improved understanding of antibody maturation,” Current Opinion in Structural Biology, 67 pp. 226-231 (2021 (PTO 892)) at p. 226, col. 2, lines 20-24.
As recently as 2020, researches were still speculating as to how to reliably identify further putative binders from antibody sequence data, see, e.g., Marks et al., “How repertoire data are changing antibody science,” J. Biol. Chem. 295(29) 9823-9837 (2020 (PTO 892)), acknowledging that “there is a vast amount of the antibody sequence space that remains unknown,” p. 9831, col. 2, para. 2.
Even though the protein sequence of ErbB3 was known in the art, this would not have translated into knowledge of the genus of antibodies that could possibly engage it. Computational and machine learning approaches for sequence-based prediction of paratope-epitope interactions are accumulating, but “it remains unclear whether antibody-antigen binding is predictable” (Akbar et al., Cell Reports 34, 108856, Mar. 16, 2021 at p. 2, col. 2, para. 2 (PTO 892)). The current state of the art continues to work toward finding an effective and efficient prediction tool for reliably assigning antibody structure based on known target epitopes. See e.g., Lo et al., “Conformational epitope matching and prediction based on protein surface spiral features,” BMC Genomics volume 22, Article number: 116 (2021 (PTO 892)) (disclosing new algorithms that calculate physicochemical properties, such as polarity, charge or the secondary structure of residues within the targeted protein sequences, and then applying quantitative matrix analyses or machine-learning algorithms to predict linear and conformational epitopes).
It is asserted that neither the specification nor the state of art at the time of filing disclosed structural features common to the members of the genus for reliably assigning different antibody structures based on sequence data for a single anti-ErbB3 clones, ab#6, which would support the premise that the inventors possessed the full scope of the claimed invention.
Enablement
(methods of prevention)
9. Claims 7-14 and 17 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 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.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
Definitions
“treat/treating” (Claims 7 and 17): the specification is explicit in the meaning covering both therapeutic and preventative/prophylactic outcomes at
[0148] The terms “treat,” “treating,” and “treatment,” as used herein, refer to therapeutic or preventative measures described herein. The methods of “treatment” employ administration to a subject, an antibody or antigen binding portion disclosed herein, for example, a subject having a disease or disorder associated with ErbB3 dependent signaling or predisposed to having such a disease or disorder, in order to prevent, cure, delay, reduce the severity of, or ameliorate one or more symptoms of the disease or disorder or recurring disease or disorder, or in order to prolong the survival of a subject beyond that expected in the absence of such treatment.
“subject” (Claims 7 and 17): is defined in the specification as a subject receiving a therapeutic or prophylactic treatment at
[0154] The term “patient” includes human and other mammalian subjects that receive either prophylactic or therapeutic treatment.
The Patent Act requires that patent Applicant describe the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek methods of prevention much less for any cancer in a subject, in vivo, where no examples or data are shown in the Application as filed. The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”)
Scope of Enablement
(methods of additive/synergistic therapy)
10. Claims 7-14 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: synergistic inhibition of ACHN tumor growth, in vivo, using Ab#6 plus erlotinib, and additive inhibition of DU145 tumor growth, in vivo, using Ab#6 plus taxol, does not reasonably provide enablement for a synergistic or additive therapeutic effect of Ab#6 with just any cancer agent against just any cancer, in vivo. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Disclosure in the Specification
The specification provides support and enablement for the claimed antibody, Ab#6 in combination with erlotinib for synergy and taxol for additivity:
[0074] FIG. 30 is a graph showing the effect of Ab #6 alone, erlotinib alone or Ab #6 plus erlotinib on the growth of ACHN xenograft tumors in nude mice. The data show that after 27 days the combination a dose of 300 ug of Ab #6 (a suboptimal dose when administered alone) plus erlotinib synergistically inhibits tumor growth to a statistically significant extent.
[0075] FIG. 31 is a graph showing the effect of Ab #6 alone, taxol alone or Ab #6 plus taxol on the growth of DU145 xenograft tumors in nude mice. The data show that after 27 days the combination of a dose of 300 ug of Ab #6 (a suboptimal dose when administered alone) plus taxol inhibits tumor growth to a greater extent than does treatment with either drug alone to a statistically significant extent.
Status of the Art for synergy
According to de Corte (PTO 892) the meaning of synergy from a patentability standpoint for methods claiming enhanced efficacy or synergy, is not predictable due to natural variation. De Corte teaches “If synergy between two (or more) substances does indeed exist, then it is probable that the synergistic relationship is specific to certain doses or, more likely, to certain ratios of doses.” As discussed above, and where synergistic results are combination specific, dose specific and administration specific, the ordinary artisan cannot not nearly conduct the experimentation to determine which combination of antibody reagents set forth in the instant claims would yield the intended endpoint of enhanced tumor regression absent undue experimentation and when faced with the degree of unpredictability associated with producing and achieving synergy for a method claimed invention.
Synergy for combination immunotherapy is unpredictable. In determining a synergistic reaction, the ordinary artisan would take a single drug and distribute it into two containers, A and B, or combine different mixtures of A and B, e.g., 10A + 0B, 9A + 1B, 5A + 5B, 1A + 9B, 0A + 10B.
A/Ae + B/Be= Z where Z= 1 is additive, Z<1 is synergy and Z>1 is antagonism, where Ae and Be are equi-effective doses of drug.
Dose response curves are rarely, if ever, linear except with ionizing radiation. Most dose response curves are hyperbolic and result from drug-receptor interactions, a binding phenomenon. Thus the solution to this problem is drugs should be compared at equi-effective doses, Ae and Be, by titrating the drug to endpoint. Any equivalent effectiveness may be used, but, 50%, the midpoint is most common. (Berenbaum Clin. Exp. Immunol. 28:1-18 (1977); Berenbaum Pharmacol. Rev. 41:93-141 (1989)); and Tallarida "Drug Synergism and Dose Effect Analysis" Ed. Chapman & Hall (2000), pp. 1-8, 10-13 and 57-71).
The specification does not teach (i) how synergy is determined, (ii) that synergy has been demonstrated across the full scope of the method claim using the recited reagents (MPEP 2164.08), (iii) that to work out the relative concentrations for the reagents to achieve synergy is not unduly burdensome, and (iv) that synergy has been demonstrated for treating the genus of cancers for the recited reagents for just any dosage regimen.
In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991).
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.
11. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 7846440.
A single invention was determined in the Restriction/Speciation of 3/4/2010 for the parent reference patent as being drawn to antibodies, compositions and methods:
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Although the claims at issue are not identical, they are not patentably distinct from each other because the inventions comprise the VH/VL CDR1-3 and/or the VH/VL for the anti-ErbB3 antibody clone, a#6, in the form of an antibody, a composition or a method of use and are rendered anticipated or obvious by the reference patent.
1. An antibody which: is an isolated full length IgG monoclonal antibody, binds to ErbB3 with a K.sub.D of about 4 nM as measured using a surface plasmon resonance assay or a cell binding assay using MALME-3M cells, and comprises a heavy chain variable region sequence as set forth in SEQ ID NO:1 and a light chain variable region sequence as set forth in SEQ ID NO:2.
2. An antibody which: is an isolated full length IgG monoclonal antibody, binds to ErbB3 with a K.sub.D of about 4 nM as measured using a surface plasmon resonance assay or a cell binding assay using MALME-3M cells, and comprises a heavy chain variable region CDR1 comprising SEQ ID NO:7; a heavy chain variable region CDR2 comprising SEQ ID NO:8; a heavy chain variable region CDR3 comprising SEQ ID NO:9; a light chain variable region CDR1 comprising SEQ ID NO:10; a light chain variable region CDR2 comprising SEQ ID NO:11; and a light chain variable region CDR3 comprising SEQ ID NO:12.
3. An antibody which: is an isolated full length IgG monoclonal antibody, binds to ErbB3, downregulates the ErbB3 receptor in MALME-3M cells so that, levels of ErbB3 on the surfaces of the cells are decreased by at least 50%, and comprises a heavy chain variable region sequence as set forth in SEQ ID NO:1 and a light chain variable region sequence as set forth in SEQ ID NO:2.
4. An antibody which: is an isolated full length IgG monoclonal antibody, binds to ErbB3, downregulates the ErbB3 receptor in MALME-3M cells so that levels of ErbB3 on the surfaces of the cells are decreased by at least 50%, and comprises a heavy chain variable region CDR1 comprising SEQ ID NO:7; a heavy chain variable region CDR2 comprising SEQ ID NO:8; a heavy chain variable region CDR3 comprising SEQ ID NO:9; a light chain variable region CDR1 comprising SEQ ID NO:10; a light chain variable region CDR2 comprising SEQ ID NO:11; and a light chain variable region CDR3 comprising SEQ ID NO:12.
5. An antibody which: is an isolated full length IgG monoclonal antibody, binds to ErbB3, exhibits an IC50 for betacellulin mediated phosphorylation of ErbB3 that is from 5.32.sup.-10M to 1.32.sup.-9M in ADRr cells stimulated with betacellulin, and comprises a heavy chain variable region sequence as set forth in SEQ ID NO:1 and a light chain variable region sequence as set forth in SEQ ID NO:2.
6. An antibody which: is an isolated full length IgG monoclonal antibody, binds to ErbB3, exhibits an IC50 for betacellulin mediated phosphorylation of ErbB3 that is from 5.32.sup.-10M to 1.32.sup.-9M in ADRr cells stimulated with betacellulin, and comprises a heavy chain variable region CDR1 comprising SEQ ID NO:7; a heavy chain variable region CDR2 comprising SEQ ID NO:8; a heavy chain variable region CDR3 comprising SEQ ID NO:9; a light chain variable region CDR1 comprising SEQ ID NO:10; a light chain variable region CDR2 comprising SEQ ID NO:11; and a light chain variable region CDR3 comprising SEQ ID NO:12.
7. An antibody which: is an isolated full length IgG monoclonal antibody binds to ErbB3, at a concentration of 63 nM, causes a decrease in heregulin mediated phosphorylation of AKT of about 100% in MALME-3M cells, and comprises a heavy chain variable region sequence as set forth in SEQ ID NO:1 and a light chain variable region sequence as set forth in SEQ ID NO:2.
8. An antibody which: is an isolated full length IgG monoclonal antibody binds to ErbB3, at a concentration of 63 nM, causes a decrease in heregulin mediated phosphorylation of AKT of about 100% in MALME-3M cells, and comprises a heavy chain variable region CDR1 comprising SEQ ID NO:7; a heavy chain variable region CDR2 comprising SEQ ID NO:8; a heavy chain variable region CDR3 comprising SEQ ID NO:9; a light chain variable region CDR1 comprising SEQ ID NO:10; a light chain variable region CDR2 comprising SEQ ID NO:11; and a light chain variable region CDR3 comprising SEQ ID NO:12.
9. The antibody of any one of claims 2, 4, 6 and 8 which, at a concentration of 10.sup.-8M, inhibits betacellulin mediated phosphorylation of ErbB3 by about 100% in ADRr cells.
10. The antibody of any one of claims 2, 4, 6 and 8 which is an IgG2 isotype antibody.
11. A composition comprising an antibody of claim 10 in a pharmaceutically acceptable carrier.
12. The composition of claim 11 wherein the carrier is suitable for injection or infusion.
13. The composition of claim 11 further comprising a second therapeutic agent.
14. The composition of claim 13, wherein the second therapeutic agent is a second antibody.
15. The composition of claim 14, wherein the second antibody is an anti-ErbB3 antibody.
16. The composition of claim 13, wherein the second therapeutic agent is an anti-cancer agent.
17. The composition of claim 16, wherein the anti-cancer agent is selected from the group consisting of an antibody, a small molecule, an antimetabolite, an alkylating agent, a topoisomerase inhibitor, a microtubule-targeting agent, a kinase inhibitor, a protein synthesis inhibitor, an immunotherapeutic, a hormone or analog thereof, a somatostatin analog, a glucocortocoid, an aromatase inhibitor, and an mTOR inhibitor.
18. The antibody of claim 10 which further exhibits one or more of the following properties: i. inhibition of epiregulin-mediated signaling through ErbB3; ii. inhibition of proliferation of cells expressing ErbB3; iii. downregulation of ErbB3 on cell surfaces; iv. inhibition of VEGF secretion of cells expressing ErbB3; v. inhibition of the migration of cells expressing ErbB3; vi. inhibition of spheroid growth of cells expressing ErbB3; vii. inhibition of heregulin binding to ErbB3; and viii. inhibition of formation of ErbB2/ErbB3 complexes.
12. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 8961966.
A single invention was determined in the Restriction/Speciation of 3/4/2010 for the parent reference patent as being drawn to antibodies, compositions and methods:
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Although the claims at issue are not identical, they are not patentably distinct from each other because the inventions comprise the VH/VL CDR1-3 and/or the VH/VL for the anti-ErbB3 antibody clone, a#6, in the form of an antibody, a composition or a method of use and are rendered anticipated or obvious by the reference patent.
1. An isolated monoclonal antibody or antigen binding portion thereof that specifically binds to ErbB3 and comprises heavy chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs: 7, 8, and 9, respectively, and light chain variable region CDR1, CDR2, and CDR3 amino acid sequences as set forth in SEQ ID NOs: 10, 11, and 12, respectively.
2. An isolated monoclonal antibody, or antigen binding portion thereof, that specifically binds to ErbB3 and comprises heavy and light chain variable regions as set forth in SEQ ID NOs: 1 and 2, respectively.
3. The monoclonal antibody, or antigen binding portion thereof, of claim 1 or 2, wherein the antibody, or antigen binding portion thereof, inhibits the migration of MCF-7 cells induced by fetal bovine serum.
4. The monoclonal antibody, or antigen binding portion thereof, of claim 3, wherein the monoclonal antibody, or antigen binding portion thereof, binds to ErbB3 with an affinity of 10.sup.7 to 10.sup.10 M.sup.-1 as measured by a surface plasmon resonance assay or a cell binding assay.
5. The monoclonal antibody, or antigen binding portion thereof, of claim 4, wherein the affinity is an affinity of 5.times.10.sup.8 to 10.sup.10 M.sup.-1.
6. The monoclonal antibody, or antigen binding portion thereof, of claim 5 wherein the affinity is an affinity of about 4 nM.
7. The monoclonal antibody, or antigen binding portion thereof, of claim 1 or 2, wherein the antibody downregulates the ErbB3 receptor on MALME-3M cells, as measured using FACS analysis.
8. The monoclonal antibody, or antigen binding portion thereof, of claim 1 or 2, wherein the antibody inhibits proliferation of ACHN cells.
9. The monoclonal antibody, or antigen binding portion thereof, of claim 1 or 2, wherein the antibody inhibits VEGF secretion by heregulin-stimulated MCF-7 cells.
10. The monoclonal antibody or antigen binding portion thereof of claim 1 or 2, wherein the antibody or antigen binding portion thereof is a human or humanized antibody or antigen binding portion thereof.
11. The monoclonal antibody of claim 1 or 2, wherein the monoclonal antibody is a human or humanized antibody; or is an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgAsec, an IgD, or an IgE isotype monoclonal antibody; or is a human or humanized IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgAsec, IgD, or IgE isotype monoclonal antibody.
12. The monoclonal antibody of claim 1 or 2, wherein the antibody is a whole antibody.
13. A composition comprising the monoclonal antibody of claim 1 or 2 in a pharmaceutically acceptable carrier.
14. The composition of claim 13, wherein the composition is a sterile aqueous solution or dispersion suitable for injection or infusion, or the composition is a sterile powder for the extemporaneous preparation of a sterile injectable solution or dispersion suitable for injection or infusion.
15. A sterile aqueous pharmaceutical composition according to claim 13.
13. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 8691225.
A single invention was determined in the Restriction/Speciation of 3/4/2010 for the parent reference patent as being drawn to antibodies, compositions and methods:
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Although the claims at issue are not identical, they are not patentably distinct from each other because the inventions comprise the VH/VL CDR1-3 and/or the VH/VL for the anti-ErbB3 antibody clone, a#6, in the form of an antibody, a composition or a method of use and are rendered anticipated or obvious by the reference patent.
1. A method of treating an ErbB3-expressing cancer in a human subject, said method comprising administering to the subject a therapeutically effective amount of a monoclonal antibody or antigen binding portion thereof that binds to human ErbB3 and that comprises a heavy chain variable region CDR1 comprising SEQ ID NO:7, a heavy chain variable region CDR2 comprising SEQ ID NO:8, a heavy chain variable region CDR3 comprising SEQ ID NO:9, a light chain variable region CDR1 comprising SEQ ID NO:10, a light chain variable region CDR2 comprising SEQ ID NO:11 and a light chain variable region CDR3 comprising SEQ ID NO:12.
2. The method of claim 1, wherein the monoclonal antibody or the antigen binding portion thereof is administered in combination with a therapeutically effective amount of a second agent, which is an anti-cancer agent other than the monoclonal antibody or the antigen binding portion thereof.
3. The method of claim 2 wherein the second agent comprises a second antibody or antigen binding portion thereof.
4. The method of claim 2 wherein the second agent is selected from: a protein synthesis inhibitor, a somatostatin analogue, an immunotherapeutic agent, and an enzyme inhibitor.
5. The method of claim 2 wherein the second agent is selected from: a small molecule targeting IGF1R, a small molecule targeting EGFR, a small molecule targeting ErbB2, a small molecule targeting cMET, an antimetabolite, an alkylating agent, a topoisomerase inhibitor, a microtubule targeting agent, a kinase inhibitor, a hormonal therapy, a glucocorticoid, an aromatase inhibitor, an mTOR inhibitor, and a chemotherapeutic agent.
6. The method of claim 2 wherein the second agent is panitumumab, trastuzumab or cetuximab.
7. The method of claim 5 wherein the second agent is paclitaxel.
8. The method of claim 5 wherein the second agent is cisplatin.
9. The method of claim 5 wherein the second agent is erlotinib or lapatinib.
10. The method of claim 1, wherein the antibody is a human antibody, a humanized antibody, a bispecific antibody, or a chimeric antibody.
11. The method of claim 1, wherein the antigen binding portion is a portion of a human antibody, a humanized antibody, or a chimeric antibody.
12. The method of claim 1, wherein the antigen binding portion is selected from the group consisting of a Fab, a Fab'2, and an scFv.
13. The method of claim 1, wherein the antibody is of an isotype is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgAsec, an IgD, and an IgE.
14. The method of claim 1, wherein the antibody or the antigen binding portion thereof inhibits betacellulin, heregulin, or TGF.alpha.-mediated phosphorylation of ErbB3 in AdrR cells.
15. The method of claim 1, wherein the antibody or the antigen binding portion thereof comprises a heavy chain variable region comprising SEQ ID NO:1 and a light chain variable region comprising SEQ ID NO:2.
16. The method of claim 5, wherein the kinase inhibitor is a tyrosine kinase inhibitor, a protein kinase B inhibitor, a phosphatidylinositol 3-kinase inhibitor, a cyclin dependent kinase inhibitor, or an MEK inhibitor.
17. The method of claim 1, wherein the antibody or the antigen binding portion thereof is administered parenterally.
18. The method of claim 1, wherein the antibody or the antigen binding portion thereof is contained in a pharmaceutical composition formulated with a pharmaceutically acceptable carrier.
19. The method of claim 18, wherein the pharmaceutical composition is in dosage unit form.
20. The method of claim 1, wherein the ErbB3-expressing cancer is a tumor selected from the group consisting of ovarian cancer, pancreatic cancer, renal cancer, prostate cancer, lung cancer, melanoma cancer and breast cancer.
14. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9487588.
A single invention was determined in the Restriction/Speciation of 3/4/2010 for the parent reference patent as being drawn to antibodies, compositions and methods:
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Although the claims at issue are not identical, they are not patentably distinct from each other because the inventions comprise the VH/VL CDR1-3 and/or the VH/VL for the anti-ErbB3 antibody clone, a#6, in the form of an antibody, a composition or a method of use and are rendered anticipated or obvious by the reference patent.
1. An anti-ErbB3 antibody comprising a heavy chain variable region comprising SEQ ID NO:1, or an amino acid sequence at least 90% identical thereto, and a light chain variable region comprising SEQ ID NO:2, or an amino acid sequence at least 90% identical thereto, wherein the antibody binds the ectodomain of human ErbB3, and wherein the antibody comprises: (a) variable heavy chain residues Tyr32 or Phe32, Va133, Trp57, Met102, Thr104, and Ile105 of SEQ ID NO: 1; and (b) variable light chain residues Asp28, Tyr32 or Phe32, and Tyr93 or Phe93 of SEQ ID NO: 2.
2. The anti-ErbB3 antibody of claim 1, wherein the antibody is an IgG2 isotype.
3. The anti-ErbB3 antibody of claim 1, wherein the heavy and light chain variable regions comprise amino acids sequences at least 95% identical to SEQ ID NO:1 and SEQ ID NO: 2, respectively.
4. A composition comprising the antibody of claim 1 in a pharmaceutically acceptable carrier.
15. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 9688761. The patent reference is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor restriction/speciation with the instant case. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims from the patent reference are drawn to the VH/VL CDR1-3 and VH/VL domains for the instant claimed anti-ErbB3 antibody clone, ab#6 or MM-121.
16. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 10273304. The patent reference is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor restriction/speciation with the instant case. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims from the patent reference are drawn to the VH/VL CDR1-3 and VH/VL domains for the instant claimed anti-ErbB3 antibody clone, ab#6 or MM-121.
17. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 8895001. The patent reference is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor restriction/speciation with the instant case. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims from the patent reference are drawn to the VH/VL CDR1-3 and VH/VL domains for the instant claimed anti-ErbB3 antibody clone, ab#6 or MM-121.
18. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 9518130. The patent reference is not afforded safe harbor protection under 35 USC 121 because it shares no continuity nor restriction/speciation with the instant case. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims from the patent reference are drawn to the VH/VL CDR1-3 and VH/VL domains for the instant claimed anti-ErbB3 antibody clone, ab#6 or MM-121.
Conclusion
19. No claims are allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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