DETAILED ACTION
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 .
The response and amendment to the claims filed 2-4-2026 has been entered into the record.
Status of Claims
Claims 1, 3, 5, 8, 10, 12-16, 27, 30, 31, 33, 44, 45, 53, 55, 69, 70, 71, 72 and 73 are pending.
Election/Restrictions
Applicant’s election of Group II, species of SEQ ID NO:2 and 4 and conjugate MMAE in the reply filed on 2-4-2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant submits that new claims 70-73 also read on the elected invention. This is not persuasive as claims 70-73 are drawn to a method of making the conjugate and not to a method of use of the conjugate for treatment of cancer by providing the conjugate per the elected Group II.
As such claims 1, 3, 5, 8, 10, 12-16, 27, 30, 31, 33, 45, 53, 55, 69, 70, 71, 72 and 73 are withdrawn from consideration. Claim 44 is under examination.
Information Disclosure Statement
The information disclosure statement has been considered. An initialed copy is enclosed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 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.
Claim 44 is rejected under 35 U.S.C. 112(a), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims are drawn to methods of treating cancer using an endolysosomal targeting conjugate that require a targeting component is configured to bind to a cell surface molecule of a selected type of tumor target cell and a cargo component where the targeting component is fused directly or indirectly to the cargo component that has efficacy for suppressing growth of the selected tumor target cell. The targeting component is configured to bind to a cell surface molecule of a target cell with a lower dissociation constant in an extracellular space than in an endolysosomal compartment of the target cell and is also configured to dissociate from the cell surface molecule in the endolysosomal compartment. Additionally, the conjugate is configured to deliver the cargo molecule to the endolysosomal compartment of the target cell. Beyond the functional language of the claim the class of targeting components broadly comprise any protein, protein fragment, protein domain including antibodies, fragments thereof and nanobodies. The breadth of the targeting components that bind cell surface molecules is enormous, even before considering the functional limitations imposed by the “configured to” language of the claims.
The term “configured to” is not defined in the claim and encompass innumerable structural changes to the targeting component and to the conjugate per se, in order to perform the requisite functions. The specification provides for no singular structure-function correlation that provides for the configured functions. While there are numerous antibodies that bind cell surface molecules, those structural changes that provide for a lower dissociation constant in an extracellular space than in the endolysosomal compartment and dissociate therefrom when present in the endolysosomal compartment are limited to two very specific changes on two known anti-HER2 antibodies having particular structures (see SG-MMAE and YS-MMAE, Figure 4Aand 4B) which are two mutations of the known antibody pertuzumab (see Table 2). The changes were particular to the pertuzumab antibody and the same changes were not performed on any other antibody that binds a cell surface molecule in order to demonstrate that the mutations provided for similar function (e.g. dissociation constant, pH dependence and function in the endolysosomal compartment). No other structural changes were made to the antibody fragment was made to provide for the configured functions of dissociation constant/pH dependence and dissociation from the cell surface molecule were apparently made. Therefore, the specification provides 2 examples of an anti-HER2 antibody MMAE conjugate that meets the “configured to” functional properties. A single structural component or motif that provide for a correlation with the claimed “configured to” is not set forth in the specification as filed. The skilled artisan given any particular targeting molecule would be unable to ascertain which changes should be made to provide for the change in binding, dissociation constant and pH properties and other functional properties of the claimed conjugate.
These generically claimed targeting and HER2 specific conjugates lack written description for the following reasons. The specification does not teach what structural changes to cell surface molecule binding antibodies or fragments thereof would necessarily provide for binding to a cell surface molecule and have the functional characteristics recited in the claims as it relates to the binding and dissociation properties. The specification does not teach what a representative number of structural changes to a representative number of antibodies or fragments thereof that bind the HER-2 cell surface molecule that would provide for the functional characteristics recited in the claims as it relates to the binding and dissociation properties in general.
The structures of the claimed targeting components comprising antibodies, antibody domains, antibody fragments, nanobodies, proteins, protein fragment or protein domains having the “configured to” properties are not adequately described. In AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., Ill USPQ2d 1780 (Fed. Cir. 2014) AbbVie had claims to functionally claimed antibodies and Centocor presented evidence that the antibodies described in AbbVie's patents were not representative of other members of the functionally claimed genus. The decision states, “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.’ Id. at 1349. We have held that 'a sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus.’ Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). Here, the claimed invention is a class of fully human antibodies that bind and unlimited chimeric and humanized variants of murine monoclonal antibody 12G4 that are only defined by their binding specificity to AMHR-II. AbbVie's expert conceded that the '128 and '485 patents do not disclose structural features common to the members of the claimed genus.”
The AbbVie decision considers how large of a genus is involved and what species of the genus are described in the patent. With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and ... cover any compound later actually invented and determined to fall within the claim's functional boundaries.”).
In the instant application, the specification and claims draw a fence around a perceived genus but the genus is not adequately described. The specification exemplifies two specific scFv antibodies that bind HER2 having the properties recited in the claims; however, the claims are not limited to these antibodies and the structural variability of the claimed genus of antibodies, antibody fragments, antibody domains, nanobodies is vast. While a number of targeting components are known to the art, no “configuration” changes thereto that provide a reasonable structure-function correlation with the functional properties as claimed has been established in the specification that is commensurate in scope with the claims. The specification does not describe representative examples of changes to a single anti-HER2 antibody, antibodies in general, nanobodies, proteins, protein domains to support the full scope of the claims. Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, states that 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, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). A review of the language of the claim indicates that these claims are drawn products whose targeting specificity relies upon the antibodies which have specific functional characteristics.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus OR of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(1), the court states, “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Thus, given the level of skill and knowledge and predictability in the art, those of skill in the art would not conclude that the applicant was in possession of the claimed genera of endolysosomal targeting conjugates based on disclosure. "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). For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly.
Further, it is not sufficient to define the genus solely by its principal biological property, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. Per the Enzo court's example, (Enzo Biochem, Inc. v. Gen-Probe Inc., 63 USPQ2d 1609 (CA FC 2002) at 1616) of a description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) couched "in terms of its function of lessening inflammation of tissues" which, the court stated, "fails to distinguish any steroid from others having the same activity or function" and the expression "an antibiotic penicillin" fails to distinguish a particular penicillin molecule from others possessing the same activity and which therefore, fails to satisfy the written description requirement. Similarly, the function of the variant as claimed does not distinguish a particular variant from others having the same activity or function and as such, fails to satisfy the written-description requirement. Applicant has not disclosed any relevant, identifying characteristics, such as structure or other physical and/or chemical properties, sufficient to show possession of the claimed genus. Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required. A description of what a material does, rather than what it is, usually does not suffice. (Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406). Possession of a genus may not be shown by merely describing how to obtain members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus, which are antibodies or fragments which have the recited characteristics pointed out above. The skilled artisan cannot provide for cancer treatment a conjugate that has not been adequately described. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. 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). 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 44 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claim 44, the claim preamble recites providing a conjugate for the treatment of cancer, but never provides the selected conjugated to a patient having cancer. The first two steps are mental "selecting” and the step of “providing” never provides the targeting conjugate to a patient having cancer having the selected type of tumor target cell. Therefore, the “providing” a targeting conjugate comprising the targeting component fused directly or indirectly to do nothing does not meet the goal of the preamble e.g. the treatment of cancer. What or to whom is the conjugate provided to ?
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 44 is rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Bhakta et al (US 2015/0098946, April 2015).
Bhakta et al teach the “known potent” antibody drug conjugate anti-HER2 pertuzumab-vc-PAB-MMAE at paragraph [0309]. The specification teaches that wild type (WT) pertuzumab inherently binds to HER2 (e.g. a cell surface molecule on tumor cells) with a lower dissociation constant in an extracellular space than in an endolysosomal compartment and has a lower dissociation constant at near neutral pH than at an acidic endolysosomal pH (see Figure 4B). Pertuzumab is inherently an IgG1 recombinant humanized monoclonal antibody, well known to the art. The conjugate is administered to a cancer tumor model in at a single IV dose of 5 mg/kg (Figure 23). As such the conjugate and method step of administering inherently meets the functional limitations of the claims and conjugate.
Conclusion
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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