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
Claims 1, 3, 4, 10, 11, 13, 17, 18, 32, 35, 36, 42, 46, 49, 50, and 75-77 are pending and being examined the merit.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/26/2026 has been entered.
Specification
The use of the term TriNKET®, BiTE®, and Nanobody® which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. All trademarks referenced herein should be identified as such with the appropriate notation:
TriNKET® (page 5, ¶ [0015]; page 6, ¶ [0017]; page 30, ¶ [00115], etc.);
BiTE® (page 5, ¶ [0015]; page 6, ¶ [0017]; page 30, ¶ [00114], etc.);
Nanobody® (page 19, ¶ [0074])
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1, 32 and 36 are objected to because of the following informalities:
“engater” should read “engager” in claim 1, part (h);
“Cusatuzumab” should read “Cuzatuzumab” in claims 32 and 36 to maintain consistency with the specification.
Appropriate correction is required.
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.
Claims 1, 3-4, 10-11, 13, 17-18, 32, 35-36, 42, 46, 49-50, and 75-77 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.
Claim 1 contains the trademark/trade name TriNKET® and BiTE®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a CD70 targeting molecule and, accordingly, the identification/description is indefinite.
Claims 3-4, 10-11, 13, 17-18, 32, 35-36, 42, 46, 49-50, and 75-77 are dependent on claim 1, and thus are also indefinite.
Rejections Maintained
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Claims 1, 3, 4, 10, 11, 13, 17, 18, 32, 35, 36, 42, 46, 49-50, and 75-77 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. This is a NEW MATTER rejection.
Base claim 1 has been amended to treat EGFR TKI resistant NSCLC that is negative for a EGFR T790M mutation comprised of administering a CD70 targeting molecule, wherein the CD70 targeting molecule is:
(a) a cell expressing a CD70 targeting chimeric antigen receptor (CAR),
(b) a CD70 targeting molecule conjugated to a toxic molecule,
(c) a CD27 ligand conjugated to a toxic molecule,
(d) a cell expressing a CAR comprising a CD27 polypeptide or fragment thereof fused to a CAR molecule, or
(e) an anti-CD70 antibody, or antigen binding fragment thereof, conjugated to a toxic molecule,
(f) an anti-CD70 single chain variable fragment (scFv),
(g) an anti-CD70 bi-specific T cell engager (BiTE), or
(h) an anti-CD70 tri-Specific natural killer cell engager therapy (TriNKET).
Applicant cited paragraph 0031, figure 7, and example 2 of the instant specification for providing support for administering a CD70 targeting molecule to treat EGFR TKI resistant NSCLC that is negative for a EGFR T790M mutation. However, figure legend (paragraph 0031) and figure 7 showed that EGFR TKI resistant NSCLC cells have increased CD70 expression in cells with and without EGFR T790M mutation. Example 2 discussed EGFR TKI resistant cells have an increased in CD70 expression and concluded that “these findings that CD70 expression is enhanced in EGFR TKI resistant cells suggests that targeting CD70 may be clinically useful in the setting of EGFR TKI resistant NSCLC” (paragraph 00216).
These sections of the specification do not states administering a CD70 molecules to treat EGFR TKI resistant NSCLC cells that is negative for the EGFR T790M mutation, where in the CD70 molecule is (a) a cell expressing a CD70 targeting chimeric antigen receptor (CAR), (b) a CD70 targeting molecule conjugated to a toxic molecule, (c) a CD27 ligand conjugated to a toxic molecule, (d) a cell expressing a CAR comprising a CD27 polypeptide or fragment thereof fused to a CAR molecule, (e) an anti-CD70 antibody, or antigen binding fragment thereof, conjugated to a toxic molecule, (f) an anti-CD70 single chain variable fragment (scFv), (g) an anti-CD70 bi-specific T cell engager (BiTE), or (h) an anti-CD70 tri-Specific natural killer cell engager therapy (TriNKET).
Other sections of the specification disclosed “[[A]]aspects of the disclosure relate to a method for treating EGFR-mutant non-small- cell lung cancer (NSCLC) in a patient comprising administering a CD70 targeting molecule to the patient. Further aspects of the disclosure relate to a method for treating an epithelial-to- mesenchymal transition (EMT)-positive NSCLC in a patient comprising administering a CD70-targeting molecule to the patient” (paragraph 0006). This and other sections of the speciation that discussed administering a CD70-targeting molecule does not distinguish treating patients with EGFR TKI resistant NSCLC cells that is negative for the EGFR T790M mutation.
Thus, the instant claimed limitations of administering a CD70 molecule to treat EGFR TKI resistant NSCLC cells that is negative for the EGFR T790M mutation, wherein the CD70 molecule is (a) a cell expressing a CD70 targeting chimeric antigen receptor (CAR), (b) a CD70 targeting molecule conjugated to a toxic molecule, (c) a CD27 ligand conjugated to a toxic molecule, (d) a cell expressing a CAR comprising a CD27 polypeptide or fragment thereof fused to a CAR molecule, (e) an anti-CD70 antibody, or antigen binding fragment thereof, conjugated to a toxic molecule, (f) an anti-CD70 single chain variable fragment (scFv), (g) an anti-CD70 bi-specific T cell engager (BiTE), or (h) an anti-CD70 tri-Specific natural killer cell engager therapy (TriNKET) lacks support in the original disclosure.
Response to Arguments
Applicant's arguments filed 6/26/2026 have been fully considered but they are not persuasive. The rejection under 35 U.S.C. §112(a) is maintained for the reasons set forth below.
In regards to the New Matter Rejection, Applicant argues that the claims are supported by the original disclosure by asserting that the specification expressly links (1) T790M-negative TKI-resistant NSCLC with (2) high CD70 expression and (3) susceptibility to CD70-targeting therapies, referencing para. [0031], Figure 7; Example 1 (para. [0235]); and Example 2 (paras. [0243-0244]).
Paragraph [0031] is a brief description of Figure 7 reporting CD70 expression measured by RNAseq and flow cytometry in EGFR TKI resistant cell lines. It reports an observation regarding cells; however, it does not describe determining the EGFR T790M status of a patient or selecting a patient for treatment on the basis of that status. Moreover, the paragraph is directed to the mechanism by which resistance arose rather than to tumor genotype. Additionally, paragraph [0031] discloses that CD70 expression was minimal in cells where acquired resistance to EGFR TKIs was mediated by secondary EGFR mutations (T790M) or MET amplification. Claim 1 recites that the NSCLC in the patient is negative for the EGFR T790M mutation, which refers to the genotype. Applicant restates this passage as teaching that CD70 is elevated in T790M-negative resistant cells but not in T790M-positive resistant cells. However, this is not what paragraph [0031] teaches. A patient whose NSCLC harbors the T790M mutation but whose acquired resistance arose through EMT falls within the population paragraph [0031] associated with elevated CD70, yet is excluded by claim 1. Conversely, a patient whose NSCLC is negative for T790M but exhibits MET amplification is encompassed by claim 1 while falling within the population paragraph [0031] identified as exhibiting minimal CD70 expression.
Paragraph [0235] of the instant specification is directed to EGFR mutant, TKI resistant tumors, wherein it states that approaches targeting CD70 may be effective for EGFR mutant, TKI resistant tumors. However, it makes no reference to the EGFR T790M mutation and does not distinguish T790M-negative from T790M positive tumors. Therefore, paragraph [0235] of the instant specification addresses element (3) of the Applicant’s arguments above with respect to the linkage with the general population of EGFR mutant, TKI resistant tumors, but not with respect to the T790M-negative subset recited in the claim(s). Additionally, paragraph [0235] teaches the selection of patients for treatment with CD70-targeting therapies by identifying EGFR mutations as a biomarker for the selection of patients to be treated with agents targeting CD70 as well as identifying the mesenchymal status as determined by gene expression or protein markers as a biomarker for selecting patients for treatment. However, a negative EGFR T790M genotype is not among the criteria identified.
Example 2 describes treating osimertinib resistant H1975 OR5 and OR16 cells with the ADCs cuzatuzumab-MMAE and vorsetuzumab-MMAE. However, Example 2 does not teach the EGFR T790M status of the H1975 OR5 and OR16 cells.
Taken together, the references in the instant specification that Applicant cites set forth two separate teachings. First, paragraph [0031] discloses that CD70 expression was elevated in certain EGFR TKI resistant cell lines and was minimal where resistance was mediated by secondary EGFR mutations or MET amplification, corresponding to elements (1) and (2) of Applicant’s asserted linkage. Paragraph [0235] and Example 2 disclose that CD70-directed therapies may be effective against EGFR mutant, TKI resistant tumors, corresponding to element (3) of Applicant’s asserted linkage. However, the specification as filed does not state that a patient whose NSCLC is negative for the EGFR T790M mutation is to be administered a CD70 targeting molecule, and does not identify T790M status as a criterion for selecting patients for such treatment. Further, Applicant acknowledges the absence of such a statement in arguing that the specification “need not explicitly recite every permutation of this teaching” and that the linkage “follows necessarily from the disclosed mechanism of action.” A description that renders the claimed invention obvious does not satisfy the written description requirement. The inquiry is whether the specification as filed reasonably conveys that the inventors had possession of the claimed subject matter, not whether a skilled artisan could have derived it from what was disclosed. See MPEP 2163.
Accordingly, the New Matter rejection is maintained.
Claims 1, 3-4, 10-11, 13, 17-18, 42, 49, 50, and 75-76 remained rejected and new claim 77 is 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. This is a written description rejection.
The claims are drawn to a method for treating a patient with EGFR-mutant NSCLC and/or EMT-positive NSCLC comprising administering a CD70-targeting molecule that inhibits CD70 activity to treat the cancer. Dependent claim 17 further limits the patient to one that has been previously treated for NSCLC via an EGFR TKI therapy comprising a list of antibodies. Dependent claim 35 further limits the CD70-targeting molecule to comprise an anti-CD70 antibody or CD70-binding fragment that is linked to a toxic molecule comprising a list of toxic molecules.
The specification discloses that anti-CD70 antibody drug conjugates, such as cuzatuzumab-MMAE or vorsetuzumab-MMAE, are a valid approach for targeting EGFR TKI-resistant cells because EGFR TKI-resistant cells are known to enhance expression of CD70. In addition, the inclusion of osimertinib alongside anti-CD70 antibody drug conjugates improved the anti-tumor cell effect (see entire document, but specifically page 55, Example 2, lines 16-22). The specification further discloses that, besides anti-CD70 antibody drug conjugates, anti-CD70 CAR-T cells, TriNKETs, EGFR-CD70 BiTEs, Axl-CD70 BiTEs, or other CD70-directed therapies alone or in combination with other treatments may be effective for EGFR mutant, TKI-resistant tumors (page 53, Example 1, lines 16-20). Finally, the specification also discloses that the secondary antibody binds to the CD70-targeting antibody while conjugated to a toxic molecule linked through a cleavable linker (page 5, paragraph 14).
However, there is insufficient written description in the specification as-filed of the genus of anti-CD70 single variable fragment (scFv) as required by the instant claims.
To satisfy the written description requirement, a patent 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. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See MPEP 2163.
Here, Applicant has claimed a method for treating a patient with EGFR-mutant NSCLC and/or EMT-positive NSCLC comprising administering a genus of anti-CD70 single chain variable fragment. The specification discloses working examples of treating EGFR TKI-resistant cells with increasing concentrations of the CD70 antibody drug conjugate cuzatuzumab-MMAE or vorsetuzumab-MMAE (page 56, Example 2, lines 16-28).
Artisans are well aware that knowledge of a given antigen (for instance CD70) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Briney et al. (Nature 2019. 566:393-399, of record) teaches that “the diversity of naïve antibody repertoire in humans is estimated to be at least 1012 unique antibodies” and that “the circulating B cell population samples only a small fraction of this diversity” (paragraph 1, lines 3-6). In other words, without complete structural information, consisting at least of both heavy and light chain CDRs 1, 2, and 3, an immune response to a single antigen can produce a vast array of unique antibody configurations. As such, the two species of specific anti-CD70 antibody disclosed in the specification is not sufficient to support the entire genus of the anti-CD70 scFv that can be administered to induce a therapeutic effect. Identifying an antibody simply on the basis of what it binds rather than by identifying the sequence/structure of the antibody in question is generally insufficient to provide sufficient written description of the antibody in question.
It does not appear based upon the limited disclosure of the anti-CD70 antibody drug conjugates cuzatuzumab-MMAE and vorsetuzumab-MMAE that Applicant was in possession of the claimed genus of the methods of treating a patient with EGFR-mutant NSCLC and/or EMT-positive NSCLC of for the composition comprising the claimed genus of anti-CD70 scFv.
In the absence of disclosure of relevant, identifying characteristics of a method of treating comprised of administering an anti-CD70 scFv, there is insufficient written disclosure under 35 U.S.C. 112, first paragraph.
Response to Arguments
Applicant's arguments filed 6/26/2026 have been fully considered but they are not persuasive. The rejection under 35 U.S.C. §112(a) is maintained for the reasons set forth below.
Regarding the written description rejection, Applicant argues that the claims satisfy the written description by asserting that the specification provides explicit written description support for anti-CD70 scFvs, referencing paras. [0013], [0101], [0015] and a non-patent literature document by Nilsson.
First, instant claim 1(f) recites “an anti-CD70 single chain variable fragment (scFv)” without any structural limitation; therefore, the claim encompasses the entire genus of scFv molecules capable of binding CD70, irrespective of sequence or structure. Applicant references paragraph [0013] of the specification, asserting that the specification does not merely disclose cuzatuzumab and vorsetuzumab as full length antibodies but it expressly contemplates and discloses scFvs derived from these antibodies. However, paragraph [0013] discloses only a subgenus defined by two parent antibodies, cuzatuzumab and vorsetuzumab, wherein the specification discloses a CD70 targeting molecule may comprise a scFv, and further discloses embodiments in which the CD70 targeting molecule comprises CDR1-3 from the heavy chain variable region of cuzatuzumab or vorsetuzumab and/or from the light chain variable region of cuzatuzumab or vorsetuzumab. Possession of a subgenus defined by two parent antibodies does not establish possession of the genus of all anti-CD70 scFvs. Written description of a genus requires disclosure of either a representative number of species or structural features common to the members of the genus such that one skilled in the art can visualize or recognize the members. See MPEP §2163(II)(A)(3)(a)(ii). Notably, the CD70-targeting species disclosed in the instant specification is a full-length antibody (or an antibody drug conjugate), wherein examples of species are disclosed in paragraphs [0012] and [0015], and working examples are disclosed in paragraphs [0243]-[0244]. However, as discussed in the 112a rejection reproduced above, no anti-CD70 scFv species are identified by sequence, structure, or name anywhere in the disclosure as filed and therefore, is insufficient to provide sufficient written description of the antibody in question.
Second, paragraph [00101] defines scFvs as comprising the VH and VL domains of an antibody present in a single polypeptide chain, optionally joined by a peptide linker. This definition, however, does not identify which VH and VL sequences confer binding to CD70, and therefore does not describe the members of the claimed genus.
Third, paragraphs [0015] and [00101] describe an scFv as a component of a CAR, not as the administered CD70 targeting molecule. Paragraph [0015] of the instant specification discloses that the CD70 targeting molecule may comprise a BiTE, a CAR, a T cell comprising a CAR, or a TriNKET. However, instant claim 1(f) does not recite a CAR, a BiTE, or a TriNKET. Instead, it recites administration of an anti-CD70 scFv as the CD70 targeting molecule itself. Moreover, description of an scFv within a larger molecule does not describe the administration of the scFv as the therapeutic agent.
Fourth, the specification contemplates variants that it does not describe. Paragraph [00102] states that the variable regions of the antigen binding domains of the polypeptides of the disclosure can be modified by mutating amino acid residues within the VH and/or VL CDR1-3 regions to improve one or more binding properties, such as affinity, and that such mutations may be introduced by site-directed mutagenesis or PCR-mediated mutagenesis. However, no mutated variant is identified, no structural feature common to operative variants is set forth, and no correlation between structure and CD70 binding is established. Moreover, this contemplates a population of anti-CD70 binding molecules extending beyond cuzatuzumab and vorsetuzumab, confirming that the claimed genus of anti-CD70 scFv is broader than the subject matter described in the specification.
Lastly, a publication that postdates the filing date cannot supply a description absent from the specification as filed. See MPEP 2163. Further, the submitted reference is authored by the named inventors and is directed to CD70-targeting CAR T and CAR NK cells employing an scFv derived from cuzatuzumab. The reference, therefore, speaks to the same subgenus already discussed and does not evidence possession of the full genus of anti-CD70 scFvs.
Accordingly, the Written Description rejection is maintained.
Conclusion
No claims are allowed.
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/J.H./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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