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
Status of the Claims
1. Claims 1-23 are the original claims filed on 4/22/2022. In the Preliminary Amendment of 12/15/2022, claims 1-6 and 8-23 are amended and claim 7 is canceled. In the Response of 11/26/2025, Claims 1, 10, 14, 18, and 20-23 are amended, and Claims 17 and 19 are canceled.
Claims 1-6, 8-16, 18, and 20-23 are all the claims.
The amendments to the claims raise new grounds for objection. The Office Action is final.
Priority
2. USAN 17/755,196, filed 04/22/2022, is a National Stage entry of PCT/
NL2020/050656, International Filing Date: 10/23/2020, claims foreign priority to NL 2024097, filed 10/24/2019.
Information Disclosure Statement
3. As of 1/14/2026, a total of three (3) IDS are filed: 4/22/2022; 12/15/2022; and 9/18/2024. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Specification
4. The objections to the disclosure because of informalities is withdrawn. Both clean and marked-up copies of the specification are provided in the response.
a) The replacement specification rectifies the deficiencies for the improper use of the term, e.g., GenBank, Oncomine, MedDRA, UniProt, ENSEMBL, OMIM, which is a trade name or a mark used in commerce.
b) The replacement specification rectifies the deficiencies for the figure legend to each of Figures 1-4 for failing to identify the sequence identifier for the nucleic acid sequence > 10 nucleotides in length and/or the amino acid sequence > 4 amino acids in length as shown in the corresponding figure.
c) The replacement specification rectifies the deficiencies for the spacing of the lines of the specification.
d) See p. 39, lines 24-25 in the as-filed version of the specification. Add the sequence identifiers for the corresponding CDR1-3 sequences shown in the text.
e) The replacement specification rectifies the deficiencies for p. 30, lines 37-38 to add the sequence identifiers for the corresponding CDR1-3 sequences shown in the text.
f) The replacement specification rectifies the deficiencies for p. 6, lines 13-16 to add the sequence identifiers for the corresponding CDR1-3 sequences shown in the text.
Claim Objections
5. The objections to the Claims 1-6 and 8-23 because of informalities are moot for the canceled claims and withdrawn for the pending claims.
a) Claims 1-6 and 8-23 are amended for consistency to recite “in a subject that has … cancer.”
b) Claim 10 is amended to recite “wherein the cancer is
c) Claims 14-15 are amended to delete the second Markush group in claim 14.
d) Claim 17 is canceled.
e) Claim 20 is amended to recite:
“The method of claim 16, wherein the variable domain for the antibody that comprises the first antigen binding site and the variable domain for the antibody that comprises the second antigen binding site comprise a light chain variable region comprising the IgVKI-39 gene segment, wherein the rearranged germline human kappa light chain is IgVK1-39*01/IGJK1*01.”
f) Claim 21 is amended to recite:
“The method of any one of the preceding claims, wherein the variable domain for the antibody that comprises the first antigen binding site and the variable domain for the antibody that comprises the second antigen binding site comprise a light chain variable region comprising a CDR1 according to SEQ ID NO: 1, a CDR2 according to SEQ ID NO: 2, and a CDR3 according to SEQ ID NO: 3, which numbering is according to KABAT.”
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 14-15, and 22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claim 22 is amended to recite the broad recitation “taxane”, and to delete the recitation “docetaxel or paclitaxel” which is the narrower statement of the range/limitation.
b) Claim 14 is amended to delete the phrase "such as".
c) Claim 22 is amended to delete the phrase "such as.”
d) Claim 22 is amended to delete parenthetical text and text defined by the term “(i.e.,..)”.
Double Patenting
7. The provisional rejection of Claims 1-6 and 8-23 on the ground of nonstatutory double patenting as being unpatentable over claims 36, 40, 49, 51, 53-56, 58-71 of copending Application No. 17/675,431 (reference application US 20220348683) is moot and withdrawn. Abandonment of record from 12/22/2025 is corroborated.
Rejections Maintained
Claim Rejections - 35 USC § 112(b)
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.
8. The rejection of Claims 9-10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is maintained.
a) A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05©.
In the present instance, claim 9 recites the broad recitation “a lung cancer”, and the claim also recites “non-small cell lung cancer (NSCLC)” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The response is incomplete. The rejection is maintained.
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
9. The rejection of Claims 1-6, 8-16, 18, and 20-23 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 is moot for the canceled claims and maintained for the pending claims.
Applicants allege the claims are amended to methods comprising administration of an antibody that comprises the CDR1, CDR2 and CDR3 sequences of the ErbB 2 specific heavy chain variable region of MF3958 and the CDR1, CDR2 and CDR3 sequences of the ErbB 3 specific heavy chain variable region of MF3178.
Applicants’ response is incomplete. Applicants have not addressed the outstanding grounds for rejection set forth in the Office Action of 5/28/2025 incorporated in full herein below. The amendments to the claims and the comments in the response do not even address the outstanding matters concerning whether and/or what light chain is paired with the VH for MF3958 and the VH for MF3178 and the demonstrated use thereof for the breadth cancer treatment.
Claim construction/ interpretation
The invention relates to a treatment using a bispecific antibody that comprises a first antigen-binding site that binds an extracellular part of ErbB-2 and a second antigen-binding site that binds an extracellular part of ErbB-3 for subjects that have a ErbB-2+/ErbB-3+ NRG1 fusion gene-associated cancer that has progressed after receiving a prior treatment. The prior treatment comprises a chemotherapy, a monospecific bivalent antibody & comprising antigen-binding sites that bind an extracellular part of ErbB-2 or an extracellular part of ErbB-3, or a prior treatment with Na tyrosine kinase inhibitor (TKI) of ErbB-2 or with a combination thereof.
“antigen-binding site”: the specification is unequivocal that the binding site can be single domain such as a VVH or VL from an antibody.
[0122] In one embodiment an antibody variable domain comprises a heavy chain variable region (VH) and a light chain variable region (VL). The antigen-binding site can be present in the combined VH/VL variable domain, or in only the VH region or only the VL region. When the antigen-binding site is present in only one of the two regions of the variable domain, the counterpart variable region can contribute to the folding and/or stability of the binding variable region, but does not significantly contribute to the binding of the antigen itself.
“treatment” or “treating”: the specification supports the prevention of progression or recurrence of extant cancer growth but does not imply that the bispecific antibody is cancer preventative in a naïve subject:
[0118] The term “therapeutic amount” or “effective amount” refers to an amount of an agent or combination of agents that provides the desired biological, therapeutic, and/or prophylactic result. That result can be reduction, amelioration, palliation, lessening, delaying, and/or alleviation of one or more of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. In some embodiments, a therapeutic amount is an amount sufficient to delay tumor development. In some embodiments, a therapeutic amount is an amount sufficient to prevent or delay tumor recurrence.
The claimed method is interpreted as requiring the bispecific antibody not only overcome tolerance of the subject to the prior art therapies but is treatment effective, in vivo, for the NRG1 fusion-gene, ErbB2+, ErbB3+ cancer.
Status of single domain antibodies in the art
The current field of art for single domain antibodies (VH or VL dAb) recognizes the potential for these structures in numerous applications as well as the unpredictability of their binding absent some engineering of residues to maintain specificity or stability. See for example, Krah et al. (Immunopharmacology and Immunotoxicology, 38:1, 21-28 (2016)):
“In contrast to the naturally evolved equivalent in camelids and sharks, early studies
revealed that single human VH domains are prone to aggregation and exhibit poor solubility, which is caused by solvent exposure of hydrophobic patches in the absence of an interacting VL domain. The unfavorable properties were tackled in a variety of
mutational approaches and initial attempts aimed at the transfer of VHH key elements that attributed aggregation resistance and good solubility to camelid VHHs.”
“Nowadays, convenient generation of human dAbs with desired properties and specificities has been achieved using molecular evolution approaches (e.g. phage display) and repertoires of I or synthetic human VH or VL dAbs. However, most of the human dAb affinity reagents have been isolated from synthetic libraries that are
usually constructed with engineered single scaffolds and CDR-based diversities.”
Kim et al. (Biochimica et Biophysica Acta 1844 (2014) 1983–2001):
“Aggregation and denaturation is a concern in the manufacturability and efficacy of human diagnostic and therapeutic antibodies, as antibody aggregation has been implicated in reduced in vivo efficacy and increased immunogenicity [30–33]. Therapeutic antibodies must possess the ability to withstand physical and chemical stresses, and mechanical agitations, such as high protein concentrations, elevated temperature, extreme pH and ionic strength, freeze drying/filtration/centrifugation,
and exposure to detergents, organic solvents and proteases [34].”
“The physical stability of an antibody encompasses both colloidal [35,36] and conformational (thermodynamic) stabilities, which governs an antibody’s resistance to aggregation and unfolding. Inter- and intramolecular forces determine a protein’s propensity to aggregate — a complex process where proteins form non-native, but energetically favorable states [37]. This process can occur through multiple pathways
depending on the proteins’ biophysical properties.”
Applicants have not characterized a single example of the single domain VH or VL for the antigen-binding site in the application and use for a cancer treatment method of Claim 1 and 23, that bind the corresponding antigens much less provide the instant claimed outcome, i.e., overcoming tolerance and therapeutic effectiveness, in vivo. The ordinary artisan could reasonably conclude that Applicants were not in possession of the claimed method invention using the single domain VH or VL antibodies meeting all of the structural and functional properties required of the claims.
Status of Selecting Common Light Chains
Claims 17(i) and/or (ii), 18(i) and/or (ii) and 19 are drawn to specific VH domains that recognize the ErbB2 (i) and/or the ErbB3 (ii) antigens, respectively.
Claim 20 is drawn the light chain variable domain from the rearranged germline human kappa light chain.
Claim 21 is drawn to a light chain variable region comprising specific CDRs and that is common to/shared with both the VH for an ErbB-2 antigen and the VH for a ErbB-3 antigen in the bispecific antibody construct.
The art recognizes the unpredictability of pairing just any light chain with just any heavy chain to effectuate a common light chain being a structural/functional equivalent to the natural VL of the VH domain.
US 20150203591 (USAN 14/417,863) realizes the complexity in selecting just any common light chains as follows:
[000134] alludes to the possible difficulty (or difficulties) in selecting a light chain, or that one that interferes with binding of one or both of the heavy chains with its antigen, or fails to associate satisfactorily with one or both of the heavy chains:
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[000135] alludes to the fact that there exists a form of light chain considered to be universal and that it contains no more than four (4) somatic hypermutations so long as it allows binding and/or activation with respect to both epitopes in its association with the heavy chains:
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Finally, [000132-000133] allude to the importance of the selection means for the light chain portion by “surveying usage statistics” to identify the most frequent light chains employed in human antibodies:
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“[T]he 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 specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
Summary of species disclosed in the specification
Applicant’s specification discloses a single antibody clone, namely, “the bispecific antibody, MF3958 × MF3178, a full length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients with Solid Tumors” (Example 1) in all of Examples 1-4. The specification does not specifically teach the VL domain for the clone but by implication, that the antibody is full, a VL domain is presumably present. Thus, it is not clear if the light chain or VL domain of the full antibody corresponds to the LC VL of either claims 20 or 21 of the instant claims. Thus, it is not clear if the light chain or VL domain of the of either claims 20 or 21 of the instant claims is common to each of the binding domains for MF3958 × MF3178.
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 most generic claims encompass any ErbB-2 (HER2) and any ErbB-3 (HER3) binding entity that is defined only by the function without an accompanying structure. The specification does not identify which VL domain, which combination of all six VLCDRs, or which subset of residues in the combination of CDRs is essential for the recited function of binding either one or both of ErbB-2 and/or ErbB-3 for the MF3958 × MF3178 clone. 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 ErbB-2 and erbB-3 having a common or shared VL domain. The disclosed species therefore does not represent the claimed genus.
Has Applicant provided a common structure sufficient to visualize the genus?
Applicant has not provided a common structure sufficient to visualize the genus of all possible bispecific antibody constructs. While the disclosure provides the examples of anti-ErbB-2 VH domains and anti-ErbB-3 VH domains the specification is deficient in showing the ability of single domain antibodies being specific in binding much less capable of overcoming tolerance in extant cancer subjects and possessing therapeutic outcomes for the genus of NRG1 fusion-gene, ErbB-2+, ErbB3+ cancers. One of ordinary skill in the art would have known which of the anti-ErbB-2 VH domains and anti-ErbB-3 VH domains could be combined into a single bispecific antibody with or without a specific or common VL domain, and that would still maintain antigen selectivity and affinity.
Even in 2021, therapeutic 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 ErbB-2/HER2 and ErbB-3/HER3 was known in the art, this would not have translated into knowledge of the genus of antibodies that could possibly engage the corresponding proteins. 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 one antibody clone, which would support the premise that the inventors possessed the full scope of the claimed invention.
The rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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, 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
10. The rejection of Claims 1, 6, 8-15,
a) Applicants allege the reference patents do not teach or suggest the claimed methods are efficacious following a failed therapy.
Response to Arguments
Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
b) Applicants allege there is no reasonable expectation of success with, nor is there any incentive provided for, this approach. Monospecific antibodies target a single receptor. Bispecific antibodies target two receptors that must be in close enough contact for antibody binding. If there is cross-reactivity between the epitopes recognized by the monospecific and bispecific antibody, switching from a monospecific therapy to a bispecific therapy may not overcome any tolerance or resistance issue. Moreover, even when there is no cross-reactivity a second therapy targeting the same receptor can be ineffective as shown in the case where patients who developed neutralizing antibodies to infliximab failed to respond to adalimimab or other TNF inhibitors. (Holmstrom et al. (2018); Exhibit A).
Response to Arguments
Applicants’ comments on mono-specificity versus bi-specificity are confusing and inapposite of what is taught/ claimed in the reference patent and instant claimed herein. Both are directed to a bi-specific comprising identical MF3958 and MF3178 antigen binding domains.
No copy of Exhibit A (Holmstrom) is on file for the prosecution history of this application. None is provided in the response nor with the IDS of record history.
The response is incomplete.
Taken together and in view of the foregoing arguments and observations, the rejection of the claims is maintained.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
11. The rejection of Claims
The reference patent is not afforded safe harbor protection under 35 USC 121 because the claim set does not share continuity or a common restriction/speciation with the instant claim set. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
12. The provisional rejection of claims
The reference application is not afforded safe harbor protection under 35 USC 121 because the claims do not share continuity or a common restriction/speciation with the claim set for the instant application. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
13. The rejection of Claims
The reference patent is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or a restriction/speciation with the claims of the instant application. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
14. The rejection of Claims
The reference patent is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or a restriction/speciation with the claims of the instant application. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
15. The provisional rejection of Claims
The reference is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or a restriction/speciation with the claims of the instant application.
The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. The rejection of Claims
The reference patent is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or a restriction/speciation with the claims of the instant application. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
17. The rejection of Claims
The reference patent is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or restriction/speciation with the claims of the instant application. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
18. The provisional rejection of Claims copending Application No. 18/419,492 (reference application US 20240158531) is moot for the canceled claims and maintained for the pending claims.
The reference is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or restriction/speciation with the claims of the instant application. The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
19. The provisional rejection of Claims
The reference is not afforded safe harbor protection under 35 USC 121 because the reference does not share continuity or restriction/speciation with the claims of the instant application.
The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
20. The provisional rejection of Claims reference does not share continuity or restriction/speciation with the claims of the instant application.
The claim sets are not restricted nor speciated from a common parent or as between themselves and are unrelated in continuity. As evidenced by Throsby et al (US 11780925 or US 12247078) set forth herein above, Throsby teaches selection criteria for patients “following a failed therapy” [Applicants’ comment on p. 11 of the Response]:
[0322] General Inclusion Criteria for Part 2 at [0344] 14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit.
[0017] Preferably, the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody, which is preferably cetuximab.
Throsby teaches methods for determining HER2/HER3 receptor density for the patient populations at
[0061] Preferably, the methods disclosed herein further comprise determining the ErbB-2 cell-surface receptor density for said cell or tumor. Patients may be classified using immunohistochemistry or fluorescence in situ hybridization. The HercepTest™ and/or HER2 FISH (pharm Dx™), marketed both by Dako Denmark A/S, and/or using a HERmark® assay, marketed by Monogram Biosciences are examples of suitable assays for determining ErbB-2 or ErbB-3 cell surface receptor density.
Throsby in the abstract “The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells.”
Throsby teaches examples of RTK inhibitors such as small molecules and antibodies
[0033] This RTK has therefore been extensively used as target for cancer therapy. Both small-molecule inhibitors targeting the RTK and monoclonal antibodies (mAbs) directed to the extracellular ligand-binding domains have been developed and have shown hitherto several clinical successes, albeit mostly for a select group of patients.
Throsby teaches and claims NRG-1 fusion gene expression of a protein comprising HRG1 EGF-like domain.
Throsby teaches subjects of the method having undergone a previous a therapy targeted towards EGFR inhibition. While EGFR, ErbB-2 and ErbB-3 are distinct proteins with different roles and functions, they are all members of the human epidermal growth factor receptor (HER) family. EGFR (HER1), HER2 (ErbB2), and HER3 (ErbB3) are all receptor tyrosine kinases. While EGFR and HER2 are often overexpressed in various cancers, they are also known to form heterodimers with HER3, which can influence the activation of downstream signaling pathways.
Examples under the decision of KSR, 550 U.S. at 418, 82 USPQ2d at 1396 to support a conclusion of obviousness include
“Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Claim 1(d)(4) of Maki is a therapeutic combination that consists of the same two elements inherent to the method invention.
Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention- Claims and teaching of Throsby is a therapeutic combination that consists of the same two elements inherent to the method invention in view of the patient selection criteria for those having failed prior therapies.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
21. No claims are allowed.
22. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
23. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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 ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643