Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of 225Ac-labeled AV203 as the species of HER3 targeting agent, and an antibody against PD-1 as the species of second therapeutic in the reply filed on 09 April 2025 is acknowledged. Applicant’s election of ovarian cancer as the species of solid in the reply filed on 15 September 2025 is also acknowledged. Claims 7 and 18-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09 April 2025.
3. The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 06 October 2023 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
5. The response filed on 15 September 2025 has been entered in full. Claims 4, 9, 17, 23 and 25-30 have been amended, and claims 7 and 18-21 have been withdrawn as indicated supra. Therefore, claims 1-30 are pending, and claims 1-6, 8-17 and 22-30 are the subject of this Office Action.
Improper Markush
6. Claims 2 and 16-17 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of radiolabeled molecules and second therapeutics is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Claims 2 and 16-17 are directed to different molecules having different structures, and thus share no structural similarity. Therefore, there is no substantial structural feature and a common use that flows from the substantial structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
7. 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. Claims 16 and 29 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.
9. Claim 16 is rejected as being indefinite for reciting “CD47 blockade”. The discussion of such at pg. 59 paragraph [0241]-[0242] is exemplary rather than limiting, and fails to breathe life and meaning into the term, and thus is insufficient to render the claims definite.
10. Claims 29 is rejected as being indefinite because it is not clear how a radionuclide labeled HER3 targeting agent can be both therapeutic and diagnostic. While one of ordinary skill in the art would understand that the same targeting agent could be used for both diagnostic purposes, the radionuclides useful for therapeutic purposes and diagnostic purposes are quite different. See for example pg. 72 of the instant Specification.
Claim Rejections - 35 USC § 112
11. 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.
12. Claims 1-6, 8-17 and 22-30 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.
13. The claims are drawn quite broadly to a method for treating a solid cancer in a mammalian subject, the method comprising: administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent. The claims also recite wherein the radiolabeled molecule comprises a radiolabel selected from 131I, 125I, 123I, 90Y, 177Lu, 186Re, 188Re, 89Sr, 153Sm, 32P, 225Ac, 213Bi, 213Po, 211At, 212Bi, 213Bi, 223Ra, 227Th, 149Tb, 161Tb, 47Sc, 67Cu, 134Ce, 137Cs, 212Pb or 103Pd, or any combination thereof. The claims also recite wherein the radionuclide labeled HER3 targeting agent comprises a monoclonal antibody comprising:(i) one or both of (a) an immunoglobulin heavy chain variable region including a CDR-H1 including SEQ ID NO:15, a CDR-H2 including SEQ ID NO:16, and/or a CDR-H3 including SEQ ID NO:17, and(b) an immunoglobulin light chain variable region including a CDR-L1 including SEQ ID NO:18, a CDR-L2 including SEQ ID NO:19, and/or a CDR-L3 including SEQ ID NO:20;(ii) one or both of an immunoglobulin heavy chain variable region including SEQ ID NO:21 and an immunoglobulin light chain variable region including SEQ ID NO:22; or (iii) one or both of an immunoglobulin heavy chain amino acid sequence of SEQ ID NO:23 and an immunoglobulin light chain amino acid sequence of SEQ ID NO:24. The claims also recite further comprising administering a therapeutically effective amount of at least one immune checkpoint therapy, a DNA damage response inhibitor (DDRi), a CD47 blockade, a chemotherapeutic agent, or a combination thereof. The claims also recite wherein the radionuclide labeled HER3 targeting agent is also specific for HER2 Thus the claims are drawn to a method of treatment utilizing a large genus of radiolabeled agents, or antibodies or antibody fragments thereof, that are only defined by the antigen to which they bind. However, the specification does not provide sufficient written description as to the structural features of the claimed genus of antibodies or antibody fragments that is encompassed by the claims, nor does it describe a representative number of species that have the recited function of being useful for treating a solid tumor in a mammalian subject.
14. A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
15. In contrast to the breadth of the claims, the specification discloses an anti-HER3 IgG monoclonal antibody consisting of heavy chain SEQ ID NO: 77 and light chain SEQ ID NO: 78 conjugated to the chelator DOTA using p-SCN-Bn-DOTA and radiolabeled with Actinum-225 which binds HER3 with high affinity (See Figure 3; pg. 22), binds to HER3-positive cancer cells NCI-H1975 and BxPC-3 (Figure 4; pg. 22), and inhibits tumor growth in a human tumor (NCI-H1975 cell) mouse xenograft model (See Figure 9; pg. 24). However, the specification does not provide sufficient written description as to the structural features of the claimed genus of radionuclide labeled HER3 targeting agents that have the same binding specificity and functional activity and be utilized in the claimed methods of treatment.
16. A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
17. It is well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression and activities. Based on the instant disclosure, one skilled in the art would not know which residues in the CDRs are critical for binding. There is insufficient guidance based on the reliance of disclosure of 1 antibody to direct a person of skill in the art to select or to predict particular residues or CDRs as essential for binding to HER3.
18. It is well established in the art that the amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff, et al. (PNAS, 1982. Vol. 79, page 1979). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum, et al. (J. Mol. Biol., 262:732-745; cited by Applicant) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column). De Pascalis, et al. (Journal of Immunology, 2002. 169:3076-3084; cited by Applicant) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column). Wu, et al. (Journal of Molecular Biology, 1999. 294:151-162) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left column) but certain residues have been identified as important for maintaining conformation.
19. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AlA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
20. While generically the structure of antibodies is known, the structure of the presently recited antibodies to be produced and screened in the instant method can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” (See p. 8, lines 3-5 of WO 2009/033743 A1). Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of claimed antibodies.
21. Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
22. An adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”). See MPEP 2163IIA3(a).
23. Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of radionuclide labeled HER3 targeting agents, nor guidance as to which of the myriad of molecules encompassed by the claimed “targeting agents, antibodies or fragments thereof would meet the limitations of the claims, particularly in view of the evidence cited supra. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
24. Furthermore, the Specification discloses that term CD47 blockade “refers to any agent that reduces the binding of CD47 (e.g., on a target cell) to SIRPa (e.g., on a phagocytic cell) or otherwise downregulates the "don't eat me" signal of the CD47-. SIRPa pathway. Non-limiting examples of suitable anti-CD47 blockades include SIRPa reagents, including without limitation SIRPa polypeptides, anti-SIRPa antibodies, soluble CD47 polypeptides, and anti-CD47 antibodies or antibody fragments.” Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of “CD47 blockades.
25. Moreover, it is noted that claims 1, 3-6, 8-11, 14-17 and 22-30 generically recite a radiolabel. While the Specification provides adequate written description for therapeutic radiolabels, including 131I, 125I, 123I, 90Y, 177Lu,186Re, 188Re, 89Sr, 153Sm, 32P, 225Ac, 213Po, 211At, 212Bi, 213Bi, 223Ra, 227Th, 149Tb, 161Tb, 47Sc, 67Cu, 134Ce, 137Cs, 212Pb or 103Pd in the claimed methods, it does not provide adequate written description for the claimed genus of radiolabels, which encompasses radiolabels that are only useful for diagnostic purposes, nor does it describe anti-HER3 antibodies having more than one radiolabel attached thereto, as recited in claim 2.
26. It is noted that while the claims here are directed to methods of using radiolabeled antibodies, rather than the radiolabeled antibodies themselves, the same standard applies with regard to the written description requirement. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916,926 (Fed. Cir. 2004):
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
In University of Rochester, the "claimed method depend[ed] upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment." Id. ( citation omitted). Similarly here, the claimed methods cannot be practiced without antibodies having the same binding specificity.
27. For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species, cannot be achieved by disclosing only one or two species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
28. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
29. With the exception of a 225Ac-labeled conjugate of p-SCN-Bn-DOTA and lintuzumab, the skilled artisan cannot envision the detailed chemical structure of the encompassed radiolabeled molecules that bind CD33, or CD33-binding antibodies or CD33-binding antibody fragments, or radiolabels, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
30. One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
31. Therefore, only a 225Ac-labeled conjugate of p-SCN-Bn-DOTA and the anti-HER3 IgG monoclonal antibody consisting of heavy chain SEQ ID NO: 77 and light chain SEQ ID NO: 78 (AV203), as well as an antibody comprising the full complement of CDRs from the heavy and light chain, but not the full breadth of the claims, meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 112 (Scope of Enablement)
32. Claims 1-6, 8-9, 11-17 and 22-26 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 methods of treating a solid cancer that expresses HER3, does not reasonably provide enablement for methods of treating every type of solid cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
33. Factors to be considered in determining whether a disclosure enables one skilled in the art to make and use the claimed invention in its full scope without resorting to undue experimentation include: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature or complexity of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. See In re Wands, 8 USPQ2d. 1400 (Fed. Cir. 1988).
34. In the instant case, the claims are broadly drawn to a method for treating a solid cancer in a mammalian subject comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent. Thus the claims encompass complex and unpredictable subject matter, involving the effects of complex biological molecules on diseased physiological states. As was found in Ex parte Hitzeman, 9 USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. This invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology”, Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert, denied, 502 U.S. 856 (1991).
35. The specification provides detailed guidance regarding an anti-HER3 IgG monoclonal antibody consisting of heavy chain SEQ ID NO: 77 and light chain SEQ ID NO: 78 conjugated to the chelator DOTA using p-SCN-Bn-DOTA and radiolabeled with Actinum-225 (225Ac-HER3-ARC) which binds HER3 with high affinity (See Figure 3; pg. 22), binds to HER3-positive cancer cells NCI-H1975 and BxPC-3 (Figure 4; pg. 22), and inhibits tumor growth in a human tumor (NCI-H1975 cell) mouse xenograft model (See Figure 9; pg. 24). However, the data presented in the Specification does not provide any guidance on the treatment of a cancer that does not express HER3. Therefore, while administration of 225Ac-HER3-ARC would be expected to treat cancers characterized by the expression of HER3, one skilled in the art would not predict that it would treat every type of solid cancer. There are no working examples provided in the instant application which demonstrate the treatment of a solid cancer that does not express HER3.
36. Thus, in view of the breadth of the claims, the lack of guidance, and the lack of working examples, the instant specification is not found to be enabling for a method of treating every type of solid cancer in a mammalian subject comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent. It would require undue experimentation and making a substantial inventive contribution for the skilled artisan to discover how to make and/or use the claimed invention in its full scope.
Claim Rejections - 35 USC § 102
37. 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.
38. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
39. Claim(s) 1, 3, 8-10, 14, 22, 27-28 and 30 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ward et al. (U.S. Pat. No. 10,519,247; issued 31 December 2019).
40. Ward et al. teach a bispecific antibody which binds HER2 and HER3, as well as said antibody coupled to a radionuclide (See column 6, lines 7-12), as well as methods for treating a solid tumor that expresses HER2 or HER3 with said conjugate, including ovarian cancer (See column 6, lines 15-27). Ward et al. also teach dosages of 0.1 mg/kg-100mg/kg (See Column 16, lines 45-63). Ward et al. also teach methods for diagnosing HER2/HER3-expressing solid tumors with said antibody with a radiolabel attached thereto (See column 6, lines 43-67). Thus, the Ward et al. reference meets all the limitations of claims 1, 3, 8-10, 14, 22, 27-28 and 30.
Double Patenting
41. 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 claims at issue 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
42. 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
43. The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
44. Claims 1, 3, 8-10 and 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 24-34 of copending Application No. 17/702,648 (reference application).
45. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims recite a method for treating a solid cancer, including ovarian cancer, comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent and an immune checkpoint therapy. The claims also recite wherein the HER3 targeting agent is a 225Ac-labeled monoclonal antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
46. Claims 1-3, 8-17 and 23-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-11, 14 and 17-28 of copending Application No. 17/293,663 (reference application).
47. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims recite a method for treating a proliferative disorder, including ovarian cancer, comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent and an immune checkpoint therapy including a PD-1 inhibitor. The claims also recite wherein the HER3 targeting agent is a 225Ac-labeled monoclonal antibody conjugated with DOTA.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
48. Claims 1-3, 8-10 and 12-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-5, 9-11, 16-17 and 20-21 of copending Application No. 17/726,296 (reference application).
49. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims recite a method for treating a proliferative disorder, including ovarian cancer, comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent and an immune checkpoint therapy including a PD-1 inhibitor. The claims also recite wherein the HER3 targeting agent is a 225Ac-labeled monoclonal antibody conjugated with DOTA.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
50. Claims 1-6, 8-17 and 23-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 and 23 of copending Application No. 18/146,149 (reference application).
51. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims recite a method for treating a solid cancer, including ovarian cancer, comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent and an immune checkpoint therapy including a PD-1 antibody. The claims also recite wherein the HER3 targeting agent is a 225Ac-labeled monoclonal antibody conjugated with DOTA.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
52. Claims 1-6, 8-17 and 23-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 15-18 of copending Application No. 18/392,556 (reference application).
53. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims recite a method for treating a solid cancer, including ovarian cancer, comprising administering to the subject a therapeutically effective amount of a radionuclide labeled HER3 targeting agent and an immune checkpoint therapy including a PD-1 antibody. The claims also recite wherein the HER3 targeting agent is a 225Ac-labeled monoclonal antibody conjugated with DOTA.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
54. No claim is allowed.
Advisory Information
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/JON M LOCKARD/Examiner, Art Unit 1647 December 23, 2025