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 .
Status of Claims
Claims 1-17 are pending and under examination.
Claim Objections
Claim 1 objected to because of the following informalities: the claim uses a comma to separate two elements. When separating or combining two elements, “and” is appropriate without the use of a comma. Appropriate correction is required.
Claims 5, 6, and 9 are objected to because of the following informalities: the claims use a comma after the term “comprises,” which is grammatically incorrect in this instance. Either no punctuation or a colon is proper. Appropriate correction is required.
Claim Rejections - 35 USC § 112b
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 1-17 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.
Claims 1 and 2 recite that administration of the molecular construct gives rise to an effective amount of lenalidomide that is “at least 1,000 times less,” or “about 10,000 times less” than an effective amount of lenalidomide or a combination of lenalidomide with a CD38 antibody “for the treatment of a tumor.” However, neither the claims nor the specification identifies the basis on which the two amounts are to be compared. In particular, it is unclear whether the difference refers to the amount administered, the cumulative amount over a treatment period, or some other measure. Furthermore, the claims encompass different tumor types having different responses to anti-CD38 antibodies and lenalidomide, and requiring different therapeutic amounts. Accordingly, it is unclear how the claimed fold difference values are to be determined across the full scope of the claims, and the metes and bounds are unclear. Claims 3-17 are included in this rejection for requiring the composition of claim 1 without correcting the indefiniteness.
Therefore, claims 1-17 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claims 9-14 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 9 recites “a linker unit” comprising a terminal spacer which “is linked to the C residue of the linking peptide of the anti-CD38 antibody.” Claim 6, from which it depends, discloses a pair of linking peptides comprising a plurality of C residues. As such, it is unclear which linker unit and which C residue is referenced in claim 9. To advance compact prosecution, claim 9 will be understood such that there are two linker units with each targeting a linker peptide, as this appears consistent with the drawings, and “the C residue” is understood to mean “a C residue.” Claims 10-14 are included in this rejection for requiring the composition of claim 9 without correcting the indefiniteness. Appropriate correction is required.
Therefore, claims 9-14 are rejected under 35 U.S.C. 112(b) as indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, and 5-17 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al., US Patent 11203614.
Claims 1, 2, and 5-17 are drawn to a method of treating a tumor by administering a molecular construct.
Of note, the instant specification defines an antibody broadly, and includes fragments that bind antigens.
Chang et al. teaches an antibody drug conjugate (ADC) comprising a 2-chain (scFV α CD38)-Fc—MBM-1 fusion protein conjugated with two Mal-Peptide-4-Lenalidomide bundles [see specification, p. 60, col. 43, example 44]. The two chain fusion protein comprises the variable heavy (VH) and variable light (VL) chains of the monoclonal antibody daratumumab (instant claim 1) linked to the N terminal of a pair of CH2-CH3 segments (instant claims 5 and 6), and further comprise an additional pair of metal binding motifs (MBMs, also known as linking peptides) fused to the C terminal of the CH2-CH3 segments [see p. 53, col. 29, example 10]. Chang et al. teaches that the two Mal-Peptide-4-Lenalidomide bundles are conjugated to the cysteine residues of the metal binding motifs [see example 44] (instant claim 1, 5, and 6). MBM-1 is disclosed to comprise the amino acid sequence ‘ACPGHA’ [see p. 58, col. 40, example 37] (instant claims 7and 8), the pair of which comprise a plurality of cysteine residues (instant claims 5 and 6). The lenalidomide bundles comprise a linear form center core containing three lysine residues, with lenalidomide molecules linked to the ε-amino groups of the lysine residues through linking arms that comprise the sequence ‘Ala-Val-PEG’ [see p. 59, col. 41, example 40] (instant claims 9, 13, 14). Chang et al. teaches that the center core comprises a maleimido-ethyl group linked to the sequence of ‘EDEDEAGGKGAGKGAGKG’ [see example 40] (instant claims 10 and 11), which further comprises at least one filler between each K residue, a terminal spacer ‘EDEDEAGG’ linked to the N terminus of the first K residue, and the other termini linked to a terminal C residue of the MBM linker peptide portion of the anti-CD38 antibody [see example 44] (instant claim 9). Chang et al. teaches that the resulting ADC selectively exhibits cytotoxic activity against CD38-positve multiple myeloma cells, including H929 and U266 cells invitro [see p. 61, col. 46, example 53].
Regarding claim 1, although Chang et al. does not expressly teach administering the ADC discussed above for the treatment of tumors or melanoma/myeloma specifically, it would have been obvious to do so with an expectation of success as the art recognized the utility of ADCs as therapeutic compositions, both anti-CD38 antibodies and lenalidomide were known therapeutics for cancers such as myeloma, and the ADC exhibited anti-tumor properties against melanoma cells in vitro (instant claims 15-17). Furthermore, the limitation of “wherein the administration gives rise to an effective amount of the lenalidomide molecules or the hydrolyzed lenalidomide molecules that is at least 1,000 times less than an effective amount of the lenalidomide molecule used alone or in combination with the anti-CD38 antibody for the treatment of the tumor” is an expected result that does not include an active step, and is interpreted as an inherent property of administering the claimed ADC to the claimed population (instant claim 1). This interpretation extends to claim 2 as it only changes the level of effectiveness (instant claim 2).
Regarding claim 12, as discussed above, Chang et al. teaches a closely related center-core sequence of EDEDE[G]AGGKGAGKGAGKG (bracketed to show missing element), having the same number and arrangement of lysine residues and the same GAG sequences separating the lysine residues. Thus, the claimed sequences differ only by the placement of a single glycine residue within the spacer region. It would have been obvious to modify the known linker sequence as a matter of routine optimization. The claimed sequence is a predictable variation of a known linker sequence, where the modification occurs in the non-functional spacer region while preserving the known lysine attachment sites and overall linker architecture. Such a modification would have been expected to retain the function of the linker because all of the critical elements remain unchanged and glycine is a known flexible component of linkers (instant claim 12).
Therefore, claims 1, 2, and 5-17 are rejected under 35 U.S.C. 103
Claims 1, 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al., US Patent 11203614, in view of Phipps et al.
The disclosure of Chang et al. is discussed above.
Chang et al. does not teach or suggest the claimed administration guidelines of claims 2 and 4.
Phipps et al. teaches administration of daratumumab to patients with relapsed/refractory multiple myeloma at doses ranging from 0.005 to 24 mg/kg [see p. 122, col. 2, par. 2] (instant claim 3). Phipps et al. teaches therapeutic effects at these doses, including dose-dependent decreases in paraprotein levels, clearance of multiple myeloma cells from bone marrow, and stable disease [see p. 122, col. 2, par. 2; see p. 123, col. 1-2]. Phipps et al. further teaches administration timelines of daily, weekly, twice-monthly, and monthly [see p. 123, col. 2, par. 1].
It would have been obvious to administer the ADC disclosed by Chang et al. above using the known dosing parameters for anti-CD38 antibodies in the treatment of cancer because the construct contains the same anti-CD38 targeting component responsible for targeting CD38 positive tumor cells. One would have reasonably expected the construct to retain the therapeutic properties associated with the CD38 binding component while providing the additional antitumor effects of lenalidomide. Accordingly, selecting a dose within the known effective range of anti-CD38 therapy would have been an obvious optimization of the treatment regimen, with a reasonable expectation of success.
Therefore, claims 1, 3 and 4 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tirone D Johnson whose telephone number is (571)272-1256. The examiner can normally be reached M-F, 9-5 ET.
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/TIRONE D. JOHNSON/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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