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 .
Claims Status
Claims 3-4, 8-10, and 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on September 11, 2025.
Claims 2, 14 and new claims 18-23 are under consideration in this office action.
Withdrawn Rejections
Any objection or rejection of record pertaining to cancelled claims 1 and 5 are rendered moot by applicant’s cancellation of said claims.
The rejection of claims 2 and 14 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of applicant’s amendment.
The rejection of claim 14 under 35 U.S.C. 112(d) as being of improper dependent form in withdrawn in view of applicant’s amendment.
The rejection of claims 2 and 14 under 35 U.S.C. 112(a) for failing to comply with the written description requirement is withdrawn in view of applicant’s amendment to limit the anti-CD20 antibody to the species rituximab.
Modified Rejection Necessitated by Amendment
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 2, 14 and new claims 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Meghdad et al, published March 9, 2018 (IDS from 11/2/2022) in view of CN103254317 (“Chen”; IDS from 11/2/2022), machine translation retrieved from Patentscope on 10/10/2025 (see PTO-892 from 10/17/2025) and AU2018320470 (“Kamii”; see PTO-892 from 10/17/2025).
The claims are directed to an antibody-drug conjugate comprising an anti-CD20 monoclonal antibody conjugated to the cytotoxic agent MMAE and the linker MC-vc-PAB, wherein the drug/antibody ratio is between 3.3 and 4.3.
Meghdad et al teaches the structure of an antibody-drug conjugate where the anti-CD20 antibody rituximab is linked to MMAE via the linker MC-vc-PAB (pg 52, column 2, para 2), as in instant claim 2. The drug/antibody ratio of this ADC is approximately 6 (figure 3; pg 53, column 1, para 3)
Meghdad et al does not teach that q (i.e. the drug/antibody ratio) is between 3.3 and 4.3.
Chen teaches an anti-CD20 antibody-MMAE conjugate, wherein the linking arm is maleimide modified valine-citrulline dipeptide (pg 2, ln 15). Each antibody can be coupled to 3-8 toxin molecules (pg 2, ln 32-33). Given that Meghdad et al teaches an ADC comprised of anti-CD20 antibody, MMAE, and MC-vc-PAB and further given that Chen teaches that an anti-CD20 antibody-MMAE conjugate can be linked to 3-8 drug molecules, it would have been obvious to one of ordinary skill to modify the ADC of Meghdad et al, with the guidance of Chen, to achieve the claimed ADC where q is 3.3-4.3. One would do so with a reasonable expectation of success, because the claimed range of q lies completely within the range taught by Chen et al. In the absence of a showing of unexpected results, such a difference would have been obvious to one of ordinary skill in the art as a routine modification of the product.
The combined teachings of Meghdad et al and Chen teach the antibody-drug conjugate comprising an anti-CD20 monoclonal antibody conjugated to the cytotoxic agent MMAE and the linker MC-vc-PAB, wherein the drug/antibody ratio is between 3.6 and 4.0. Furthermore, as Meghdad et al in view of Chen teach an ADC with a range of antibody-drug ratio of 3-8 and, thus, teach the limitation of instant claim 2 and new claims 21-12 directed to a q (antibody-drug ratio) of 3.3-4.3, 3.6-4.0, 3.7, 3.9, and 3.8 as well as the pharmaceutical formulation. This combination of references, however, does not teach a pharmaceutical composition comprised of the excipients and concentrations thereof of instant claim 2 and new claims 18-20.
Kamii teaches an antibody-drug conjugate comprising MMAE [0004] and stable compositions thereof. Kamii teaches a stable composition comprising an ADC with a concentration of 20 mg/ml ADC, 10 mM histidine, 9% sucrose, 0.02% or 0.03% polysorbate 80 (i.e. Tween-80), and pH 6 (pg 67-68), as in the preparation of instant claim 2 comprised of 1 to 60 mg/ml ADC, 5-35 mM histidine, 2-10% sucrose, and 0.01-0.1% Tween-80 and pH 5.8-6.2. Kamii also teaches an ADC formulation comprised of the same excipients with a pH range of 5.8-6.1 (pg 68-69). The claimed concentrations completely overlap with those of Kamii. The concentrations of the ADC and excipients of Kamii also overlap with the narrower concentrations of the ADC and excipients in new claims 18-20.
Given that Meghdad et al in view of Chen teach the claimed ADC and Kamii teaches a pharmaceutical formulation for ADCs, it would have been obvious to use the formulation of Kamii with the antibody-drug conjugate of Meghdad et al in view of Chen, because the artisan has good reason to pursue the known options within their technical grasp to obtain predictable results. Such would amount to the simple substitution of one structurally equivalent element for another (i.e. the ADC of Meghdad for the ADC of Kamii) to obtain predictable results. The motivation to do so comes from Kamii, which teaches that the formulation was associated with decreased protein aggregation and decreased generation of decomposition products (pg 29), which are desirable feature when developing a protein formulation.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one product, and a person of ordinary skill would recognize that it would be used in similar products in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to one of ordinary skill in the art to apply a known pharmaceutical formulation to a known product that is ready for improvement to yield predictable results. Thus, the prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Response to Arguments
Applicant's arguments filed January 12, 2026 regarding the rejections under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant asserts that the combination of cited references fail to teach or suggest a formulation comprising the claimed ADS and a histidine buffer of pH 5.8-6.2 (remarks, pg 12). Further, applicant provides WO2019/197428 to demonstrate that the prior art teaches away from using a ADC formulation with a pH of 5.8-6.2. In brief, WO‘428 teaches that the stability of ADC formulations of pH 6.5 is superior to formulations with pH of 5.5 (remarks, pg 14). However, in the modified rejection set forth above, it is clear that Kamii also teaches a different ADC formulation with the narrower pH scope now claimed. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Any evidence of unexpected results, however, may render the claims nonobvious. In the absence of unexpected results, such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical.
Applicant argues that the claimed subject matter is unexpectedly superior, because stability is greater at pH 5.8 and 6.2 compared to pH 6.7 and 7.0 (remarks, pg 15-17). However, this argument is not persuasive for nonobviousness because the identification of the pH could have been achieved through routine optimization. Kamii recognizes that pH is a result-effective variable, which can be routinely determined and optimized in the pharmaceutical arts. Routine optimization is comprised of methods that are well-understood and conventional activities previously known to the industry. When considering whether the determination of the optimum or workable ranges of a variable (e.g., pH) might be characterized as routine experimentation, the particular parameter must first be recognized as a result-effective variable (see MPEP 2144.05(I)-(II). KSR International Co. v. Teleflex held that “obvious to try” was a valid rational for an obviousness finding when the invention is directed to a result-effective variable. In this case, an artisan prior to the effective filing date of the invention would have a reason to vary the pH of an antibody formulation because pH was recognized as a result-effective variable in the field of ADC formulation with respect to stability (see Kamii). Thus, one of ordinary skill in the art would have a reasonable and predictable expectation of arriving at the claimed formulation.
Because Meghdad et al in view of Chen and Kamii teach the ADC and the ADC formulation concentrations and pH values that fall within the claimed range, it would have been obvious to the ordinary artisan to select the recited carriers, excipients, surfactants, and stabilizers of Kamii to produce a stable pharmaceutical formulation of the ADC of Meghdad et al. One would have been motivated to do so, in view of the art-recognized need to optimize formulations of therapeutic ADCs and have a reasonable expectation of success, based on the knowledge and skill in the art. One of ordinary skill in the art would expect, in view of the routine nature of the experimentation involved, that using the formulation of Kamii with the ADC of Meghdad et al in view of Chen would provide a stable and quality formulation necessary to maintain the bioactivity of the ADC during long-term storage.
As stated in MPEP 2144.05, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Applicant argues that Chen and Kamii are directed to ADC of different antibodies and that Kamii teaches a different linker from those claimed, and thus it would not be obvious to use combine the cited references, as there is no motivation to do so (remarks, pg 13). However, while Wang does not teach a pharmaceutical formulation of the claimed ADC, it is not necessary for this secondary reference to do so, because the 103 rejection was based on the combined teachings of Meghdad et al, Chen, and Kamii. It would have been obvious to one of ordinary skill in the art to modify the composition of Kamii using the ADC of Meghdad et al in view of Chen to achieve the desired results, especially since the formulation is comprised of components at concentrations that routinely used in the art of antibody pharmaceutical formulation. Meghdad et al in view of Chen and Kamii teach the ADC and the pH values that fall within the claimed range.
Furthermore, absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. “Good science and useful contributions do not necessarily result in patentability.” PharmaStem Therapeutics, Inc. v. Viacell, Inc., 491 F.3d 1342 (Fed. Cir. 2007).
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675