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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/12/2026 has been entered.
The rejection under improper Markush Grouping is maintained:
Claim Rejections - Rejection under the Judicially Created Doctrine of Improper Markush Grouping
Claims 44 and 65-71, 73-75, 77 remain rejected under the judicially created doctrine of "improper Markush grouping". The Markush group of Formula (VIII) contains a plethora of nested variables. This is an improper grouping of alternatively useable species. MPEP 803.02 describes a Markush grouping as " ... "selected from the group consisting of A, Band C." 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 compounds of Formula (III) do not share a "single structural similarity". 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 there is no common structure that occupies a significant portion of the compounds of Formula (III) since the entire structure is highly variable:
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138
256
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See definitions in claim 44.
Additionally, as a result of the wide range of compounds possible by the instant Markush formula, each compound 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 compounds 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 in the art and taught in the first chapter of the organic text CAREY, FA. Organic Chemistry 6th Ed. McGraw Hill. 2006, chapter 1, p. 9. Therefore, in the absence of evidence to the contrary, all compounds 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.
Applicant argues that claim 44 has been amended to redefine the variables in Formula (III) including W, L1, L₂, V₁, and V₂ so that the compounds of Formula (III) share a substantial common chemical structure. As described in the specification of the present application, an antibody-drug conjugate (ADC) which consists of an antibody linked to a cytotoxic drug via a releasable linking molecule has been used for the treatment of cancers, infection, autoimmune disorder and the other drug-resistant diseases.
However, all the groups in Formula (III) are still highly variable. Despite the amendments, a common chemical structure which occupies a large portion of Formula (III) cannot be identified. Therefore, the rejection is maintained.
The rejection under section 102 is maintained:
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, 65-69, 71, 73, 74 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jain et al., Pharm Res (2015) 32:3526–3540 (Jain).
Jain teaches the mc-vc-PABC-MMAE conjugate at page 3531:
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836
1140
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The above conjugate anticipates the rejected claims wherein:
V2, L2, W-D2 are absent (w’ is “absent”);
V1 is mc:
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78
414
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see new claim 66;
L1 is val-cit (vc, wherein L1 is (Aa)r r = 2);
W is the self-immolative spacer PBAC;
D1 is MMAE; and
Q1 is side chain citrulline (vc).
Some of rejected dependent claims recite groups that are not present in the above structure but may be absent in the definitions recited in claim 44. The ependant claims do not explicitly require these groups to be present, and therefore, these structures are not actually required by the dependent claims.
Applicant argues that claim 44 of the present application specifically recites that "w and w' are independently 1, 2 or 3." That is, w' is not 0 (absent). As such, the conjugate disclosed in Jain et al. does not meet all the features recited in claim 44. In other words, Jain et al. does not teach or anticipate claim 44.
However, the requirement that w' is not 0 is present in the conjugate of Jain. Specifically, the self immolative linker, PAB, is present in the conjugates of Jain which corresponds to the instant group W, and w’=1. Therefor the rejection is maintained.
The rejection under section 112(b) is withdrawn in view of Applicant’s amendments. The following are new grounds of rejection:
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 44 and 65-77 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.
L1 and L2 must bind at least 3 groups, but the groups that define L1 and L2 cannot bind at least 3 groups since they do not have at least 3 open valencies.
In claim 66 it is unclear if any of W, V1 or V2 can have the recited groups, or if the recited groups make up W, V1 and V2.
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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