DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's preliminary amendment filed on 12/28/2023 is acknowledged.
Claims 64-81 are pending.
3. 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.
4. Claims 64-81 are 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 regards as the invention.
(i) Claim 64 is indefinite in the recitation of a “first” chimeric protein, because the second, etc. chimeric protein(s) is/are not defined.
(ii) Claim 64 is further indefinite in the recitation of a “sequence selected from SEQ ID NO: 1 or 2,” as being in improper Markush format. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" rather than "or" in listing the species. See MPEP 803.02.
(iii) Claims 65, 74 and 77 are indefinite in the recitation of (the) signaling agents lacks proper antecedent basis in the base claim.
(iv) Claim 71 is indefinite in the recitation of “a microprotein,” because the nature, properties, or identity of microproteins within the scope of the claim are unknown.
(v) Claim 71 is further indefinite in the recitation of exemplary language “e.g.,” because it is unclear whether the limitation(s) following the language are part of the claimed invention. See MPEP § 2173.05(d).
(vi) Claims 65-81 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
5. The following is a quotation of 35 U.S.C. 112(d):
REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
6. Claim 74 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 74 depends on claim 64 which is recites one or more mutations comprised within human IFNa2, whereas claim 74 encompasses mutations in one or more generically recited “signaling agents.” Therefore, dependent claim 74 may be infringed without infringing the base claim, and as such, claim 74 fails to further limit, and fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place it in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
7. The following is a quotation 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.
8. Claims 64-81 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a method for treating cancer comprising administering a chimeric protein comprising:
a human IFNa2 having at least 98% identity with SEQ ID NO: 1 or 2 and having one or more mutations at positions 144-154, and
at least one targeting moiety comprising a recognition domain which specifically binds to a generically recited non-cellular tenascin tenascin-CA1,
wherein the one or more mutations confer reduced affinity or activity to IFNα2 that is restorable by attachment to the one or more targeting moieties,
does not reasonably provide enablement for a method for treating cancer comprising administering a chimeric protein comprising:
(i) a human IFNa2 having one or more mutations at positions 144-154, in the absence of recitation of any functional properties of the mutant molecule; or
(ii) a human IFNa2 having at least 95% identity with SEQ ID NO: 1 or 2; or
(iii) a targeting moiety comprising a recognition domain which specifically binds to a generically recited non-cellular “tenascin molecule.”
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 use the invention commensurate in scope with these claims without undue experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
The specification describes experiments indicating that in a mouse B16 melanoma model, a chimeric protein comprising Q124R mutant interferon fused to anti-mouse tenascin-CA1 VHH reduced tumor growth while being less toxic than wild-type interferon (Example 1).
(i) Claim 64 recites IFNa2 having at least 95% identity with SEQ ID NO: 1 or 2 and having one or more mutations at positions 144-154. Each of SEQ ID NOS: 1 and 2 is 165 amino acids-long, i.e. the claim encompasses IFNa2 variants with up to 8 mutations at positions 144-154. A skilled artisan would be cognizant of the fact that as a general rule, most mutations inactivate functions of a protein. Therefore, in the absence of a limitation specifying some functional properties that mutant IFNa2 must possess, most IFNa2 embodiments within the scope of the claim would be ineffective to treat cancer.
Given the low expectation of success, the resource-intensive nature of the required experimentation and the risks involved, a person skilled in the art would reasonably conclude that this experimentation would be unnecessarily, and improperly, extensive and undue.
(ii) As noted in subsection 8(i) above, IFNa2 variants with the scope of claim 64 can have up to 8 mutations (the proviso that at least one of the mutations is at positions 144-154 does not significantly reduce the number of possible variants). Substituting 1 amino acid with each of the other amino acids or a deletion in a 165 amino acid-long polypeptide results in 20x165=3,300 variants; substituting 2 amino acids yields (20x164)x3,300=10,824,000, or over 10 million variants; substituting 8 amino acids produces over 1020 variants.
To make and use the invention as claimed, a person skilled in the art would have to produce variant polypeptides within the cope of the claims and test them for their ability to treat cancer, or for some property which correlates with the ability to treat cancer. The number of compounds that can be screened by present-day ultrahigh throughput methods does not exceed 109, or one billion variants (e.g. Gantz et al. 2024).
Based on this, a skilled artisan would inescapably conclude that the number of variant polypeptides which those skilled in the art would need produce and test for the requisite functional properties is vastly beyond the reach of technology available at present, and for years to come. Accordingly, the required experimentation would be unnecessarily, and improperly, extensive and undue.
(iii) Claim 64 encompasses chimeric proteins comprising a recognition domain which binds to any non-cellular tenascin molecule. A person of skill in the art would be aware that among the various forms of tenascin, which include tenascin-C, tenascin-R, tenascin-X, and tenascin-W, only tenascin-C expression is associated with tumor tissues (as reviewed e.g. by Chiovaro et al. 2015). Based on this, a skilled artisan would reasonably conclude that chimeric proteins that bind to tenascins other than tenascin-C would be ineffective to treat cancer. Accordingly, practicing the method as claimed would most likely be unsuccessful, and so experimentation to that end would be unnecessarily, and improperly, extensive and undue.
9. 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)(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.
10. Claims 64-81 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Tavernier et al. (US 20190352406; see entire document).
It is noted that during prosecution of application USSN 16/301299, now US Patent No. 11753463, of which the present application is a continuation, Applicant provided a statement of common ownership of Tavernier (Applicant’s submission dated 06/12/2023), invoking the Prior Art Exception under 35 U.S.C. 102(b)(2)(C), thereby disqualifying Tavernier as prior art under 35 U.S.C. 102(a)(2).
It is further noted that affidavits and declarations filed during prosecution of the parent or priority application(s) do not automatically become a part of the record of a later-filed application. Where it is desired to rely on an earlier filed affidavit, Applicant should make the remarks of record in the later application and include a copy of the original affidavit filed in the parent application.
Tavernier teaches a method of treating cancer comprising administering a chimeric protein comprising:
a human IFNα2 having at least 98% sequence identity with SEQ ID NO: 86 or 87, having one or more mutations at positions R149, L153, and M148,
a targeting moiety that binds Clec9A, and
an additional targeting moiety (e.g. claims 73, 84 and 88),
wherein the additional targeting moiety binds tenascin-CA1 (e.g. [0309]-[0310]).
SEQ ID NOS: 86 or 87 are identical to instant SEQ ID NOS: 1 and 2, respectively (see SCORE).
Tavernier further teaches that IFNa2 comprises mutations M148A, R149A, and/or L153A (e.g. claim 74), and has reduced affinity or activity as compared to wild type human IFNα2, which is restorable by the targeting moiety (e.g. claim 83). The targeting moieties are single-domain antibodies such as VHH (e.g. claims 78-80), and connected to IFNα2 with linkers (e.g. [0320]-[0335]).
Limitations of claims 66-68 are taught by Tavernier e.g. at [0387], and limitations of claims 80-81 are taught e.g. at [0185]-[0186]. Accordingly, Tavernier teaches all of the limitations of claims 64-78 and 80-81.
Claim 79 is included in the rejection, because there is no manipulative difference between the method taught by Tavernier and the instantly claimed method; therefore, the outcomes of practicing the methods are inherently the same.
11. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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.
12. Claims 64-65 and 69-81 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11753463 .
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of US ‘463.
The present application was filed as a continuation of USSN 16301299, which issued as US ‘463.
Claims 1 and 11 of US ‘463 recite a method of treating cancer comprising a chimeric protein within the scope of instant claims. Specifically, the limitations of instant claims are recited in the following claims of US ‘463:
Instant claims US ‘463
64-65, 69-70, 74 1, 11
71-73 2-3
75-76 5-6
77-78 6-7
79 12
80-81 13
13. Conclusion: no claim is allowed.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644