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 .
Claim Rejections - Rejection under the Judicially Created Doctrine of Improper Markush Grouping
Claim 14 is rejected on the basis that it contains 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 doctrine of improper Markush grouping is a principle that prevents applicants from claiming widely disparate alternatives in a single "Markush-style" claim. To be proper, grouped elements must share a single structural similarity and possess a common use. The examiner respectfully directs the Applicant's attention to MPEP 803.02 shown below for convenience:
"A Markush-type claim recites alternatives in a format such as "selected from the group consisting of A, Band C." See Ex parte Markush, 1925 C.D. 126 (Comm'r Pat. 1925). The members of the Markush group (A, B, and C in the example above) ordinarily must belong to a recognized physical or chemical class or to an art-recognized class. However, when the Markush group occurs in a claim reciting a process or a combination (not a single compound), it is sufficient if the members of the group are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. Inventions in metallurgy, refractories, ceramics, pharmacy, pharmacology and biology are most frequently claimed under the Markush formula but purely mechanical features or process steps may also be claimed by using the Markush style of claiming. (See MPEP § 2173.05(h))."
Furthermore, the members of a proper Markush grouping " ... ordinarily must belong to a recognized physical or chemical class or to an art-recognized class." MPEP 803.02 also states that members of a Markush grouping are " ... sufficiently few in number or so closely related that a search and examination of the entire claim can be made without serious burden." This paragraph of the MPEP is shown below for convenience: "If the members of the Markush group are sufficiently few in number or so closely related that a search and examination of the entire claim can be made without serious burden, the examiner must examine all the members of the Markush group in the claim on the merits, even though they may be directed to independent and distinct inventions. In such a case, the examiner will not follow the procedure described below and will not require provisional election of a single species. (See MPEP § 808.02.)"
A Markush claim contains an "improper Markush grouping" if:
1. The species of the Markush group do not share a "single structural similarity,"
- Meaning they do not belong to the same recognized physical or chemical class
or same art-recognized class (see explanation supra), or
2. The species do not share a common use,
- Meaning they are not disclosed in the specification or known in the art to be
functionally equivalent.
If 1 or 2 above apply to a Markush grouping, a rejection under the judicially approved "improper Markush grouping" doctrine is proper.
The CRD in claim 14 have no common peptide core due to the wide range of combinations. For a Markush grouping to be proper, the alternatives represented by the grouping must have a "significant structural element that is shared by all of the alternatives" or the species must all share a common use and recognized as "functionally equivalent". A significant structural element that is shared by all of the alternatives refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. Each alternative does not have a common chemical structure which occupies a large portion of the structure or have a structurally distinctive portion in view of the prior art which is essential to the claimed common activity/properties.
Here, claim 14 does not offer any commonality between the peptides prepared from the CDR combinations.
Additionally, as a result of the wide range of combinations possible by the instant CDR’s, each peptide does not belong to the same recognized physical or chemical class or to the same art-recognized class and no credible evidence for a common use amongst all claimed compounds exists. A person of ordinary skill in the art would understand that peptides with such greatly varied structure cannot be expected to have predictable properties. This is a central concept to basic organic chemistry and common knowledge of those with ordinary skill. Therefore, in the absence of evidence to the contrary, all peptides within the metes and bounds of the extraordinarily large Markush grouping of the instant claims cannot be individually envisioned and each expected to be functionally equivalent.
This rejection may be overcome by either amending the claims to include only the species that share a single structural similarity and a common use such as the compounds which have a constant core and are clearly enabled by the instant specification.
Claim Rejections - 35 USC § 112
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 3, 5, 6, 8-28, 30-32, 34 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.
The claims and specification do not provide structural or functional definitions of “cold tumor”.
The claims are replete with preferred terminology (e.g.). It is unclear if Applicant intends to limit the claims to the preferred embodiments.
It is unclear what sequences Applicant considers CDR’s in claim 13
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 3, 5, 6, 8-28, 30-32, 34 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/178101 (WO 101) or Wang et al., (2018); Cancer Res. 78(13 S):LB306 (Wang) or Ratte, (2019); J. Exp. Clin. Caner Res. 38(1):255 (Rotte) or Marabelle et al., (2013); Clin. Cancer Res. 19(19):5261-5263 (Marabelle) or WO 2018/170133 (WO 133); each in view of:
WO 2018/195552 (WO 552).
The primary references teach treating cancer by administering an oncolytic virus capable of expressing a first antibody molecule that specifically binds to CTLA-4; and a second antibody molecule that specifically binds to PD-1 and/or PD-L1:
WO 101, example 10, provides for the treatment of cancer using a combination of intratumorally injected oncolytic virus expressing a CTLA4 antibody, and systemic administration of anti-PD1/PO-L1 blockade antibodies. This reference provides for the treatment of cancer using a combination of intratumoral injection of an oncolytic virus expressing a CTLA4 antibody, and systemic administration of anti-PD1/PD-L1 blockade antibodies. The virus is a mutant vaccinia lacking functional TK.
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Wang provides a concrete oncolytic vaccinia vector expressing a CTLA-4 antibody for intratumoral delivery; it reports that it is safe and effective to enhance antitumor therapy (in models).
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Rotte teaches the use of combined CTLA-4 and PD1 blockade for the treatment of cancer; it reports the problem of bad side effects of systemic CTLA-4 antibody therapy.
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Marabelle teaches that anti-CTLA-4 therapy is better and causes less toxicity if the antibody is delivered intratumorally.
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WO 133 teaches the treatment of cancer, including cold cancers, using an oncolytic virus and a CTLA-4 blocker; or using the oncolytic virus and a PD-L1 blocker.
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The primary references may not provide treatment of a cold cancer, using CTLA-4 and PD1/PD-L1 blockade and oncolytic virus, wherein the CTLA-4 blocking antibody is encoded by the oncolytic virus itself.
However, WO 552 [237]-[238] reports treatment of a model tumor by injection of CTLA-4 antibodies, PD-1 antibodies and an oncolytic virus:
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At [231] it is foreseen to use the regimen also in cold cancers, predicted to respond because the virus will turn them into hot cancers.
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In this way, those of ordinary skill could have applied an oncolytic virus capable of expressing a first antibody molecule that specifically binds to CTLA-4; and a second antibody molecule that specifically binds to PD-1 and/or PD-L1in a predictable fashion for the purposes of treating a cold tumor. As outlined above, the primary references teach treating cancer by administering an oncolytic virus capable of expressing a first antibody molecule that specifically binds to CTLA-4; and a second antibody molecule that specifically binds to PD-1 and/or PD-L1. WO 552 is added for the proposition that this method of treatment is applicable to cold tumors. Specifically, WO 552 teaches that the particular known technique of treating cold tumors with CTLA-4 antibodies, PD-1 antibodies and an oncolytic virus was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to methods of providing CTLA-4 antibodies with an oncolytic virus would have yielded predictable results. Accordingly, treating cold tumors with the recited method would have been prima facie obvious.
The claims recite functions of the antibodies. However, the references teach administration of the recited antibodies and any observed effect is an invariable aspect of this administration, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”).
The claims also recite SEQ ID NO’s of the antibodies and vaccina virus that may not be explicitly taught by the references. However, the references substantially teach the recited antibodies and virus. The molecular structures and sequences of these antibodies and viruses are well known. Therefore, in the absence of any unexpected result, the recite anti-CTLA-4, andti-PD-1/PD-L1 antibodies and virus would have been prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646
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