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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 4, 2026 has been entered.
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Claims 3-4, 8-10, and 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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, 18-23 and new claim 24 are under consideration in this office action.
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 18-23 and new claim 24 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 claims 2, 18-20, and new claim 24.
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), as in the new limitation of claim 24 drawn to pH of 5.8. The claimed concentrations of the excipients and pH of the histidine buffer 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.
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).
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 June 4, 2026 and June 5, 2026 regarding the rejections under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant asserts that the claimed antibody-drug conjugate (ADC) formulation achieves superior and unexpected technical effects that would not have been reasonably predicted by the ordinary artisan based on the prior art teachings (remarks, pg 10). Specifically, applicant has identified a specific pH range where the formulation exhibits superior stability at 1 week, as assessed by monomer content and aggregate content levels in the sample (pg 11-12). Because Kamii teaches that pH has a limited effect on monomer and aggregate content, applicant concludes that pH variation has a limited impact on stability and the results associated with the claimed formulation are unexpected (remarks, pg 11-15). However, Kamii expressly teaches the composition and pH range for the claimed ADC formulation and teaches methods for assessing ADC stability. The pH range is not a newly discovered parameter or a value outside the prior art teachings. Moreover, selecting and optimizing the pH of an ADC formulation represents routine optimization of a result effective-variable. Kamii teaches pH values [pH 4.0-7.0 (pg 8) and pH 5.8 (pg 87)], and metrics for assessing the stability of liquid formulations (pg 78), demonstrating that Kamii recognizes pH of the formulation as a result-effective variable, which one would modify in order to achieve the desired stability. Where the prior art identified pH as a formulation parameter and provides a range encompassing the claimed range, optimization of that parameter to achieve improved stability does not, without more, render the resulting formulation non-obvious. Evidence of improved or superior stability is not sufficient to establish non-obviousness, because the improvement is a matter of degree and not kind.
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). An exception in the case where the prior art teaches “range that is so broad in light of the dissimilar characteristics of the members of the range as to not invite optimization by one of skill in the art” (MPEP 2144.05.III.D). In the instant case, the narrow range claimed is taught by Meghdad in view of Chen and Kamii and properties related to stability have been considered.
In the response filed June 5, 2026, applicant addresses remarks from the Advisory Action filed June 1, 2026. Applicant’s arguments (pg 10-11) are persuasive, and any commentary related to the linear changes in stability related to pH in Kamii has been removed from the discussion. This concession does not, however, negate the finding of obviousness.
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. 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.
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. Thus, one of ordinary skill in the art would have a reasonable and predictable expectation of arriving at the claimed formulation. The rejection under 35 U.S.C. 103 is maintained.
Conclusion
No claim is allowed.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
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