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 Status
Applicant’s amendments and remarks, filed 06/25/2026, are acknowledged.
Claims 1-29, 31, 32, 35-41, 43, 45-47, 52, and 53 are canceled.
Claims 30, 33, 34, 44, and 48-51 are amended.
Claims 54-59 are new.
Claims 30, 33, 34, 42, 44, 48-51, and 54-59 are pending.
Claims 48, 51, 56, and 59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/17/2025.
As such, claims 30, 33, 34, 42, 44, 49, 50, 54, 55, 57, and 58 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/25/2026 has been entered.
Withdrawn Objection
The specification objections are withdrawn. Issues regarding minor informalities and trademarks/names have been sufficiently addressed through amendments to the specification on 06/25/2026.
The drawing objections are withdrawn. Issues regarding minor informalities have been sufficiently addressed through amendments to the specification on 06/25/2026.
Withdrawn Rejections
Applicant’s arguments, see page 11, filed 06/25/2026, with respect to claims 30-34, 40-42, 44, 49-50, and 52-53 rejected under 35 USC 112(b) as allegedly being indefinite have been fully considered and are persuasive. The issue regarding the claims comprising indefinite language have been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 31-32, 40-41, and 52-53 are canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s arguments, see pages 11 and 12, filed 06/25/2026, with respect to claims 30-34, 40-42, 44, 49-50, and 52 rejected under 35 USC 112(a) as allegedly lacking written description and claims 30-34, 42, 44, and 49-50 rejected under 35 USC 112(a) as allegedly failing to comply with the enablement requirement have been fully considered and are persuasive. The issue regarding the specification failing to disclose Applicant’s possession of the claimed method of treating have been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 31-32, 40-41, and 52-53 are canceled thus rendering the rejection moot. As such, the rejections under 35 USC 112(a) are withdrawn.
The double patenting rejections are modified in favor of the new limitations added in the amendment filed 06/25/2026. Applicant’s arguments, see pages 15 and 16, filed 06/25/2026, with respect to the double patenting rejections have been fully considered.
However, claims 30-34, 40-42, 44, 49-50, and 52 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 65-88 of copending Application No. 18/268,168 in view of Throsby et al and Prewett et al have been fully considered and persuasive. As such, the provisional double patenting rejection is withdrawn.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
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 54 and 55 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 54 and 55 recite the transitional phrase “having”, the scope of which is not defined by the specification. As such, according to MPEP 2111.03(IV), the term will be interpreted as an open-ended transitional term, similar to the transitional phrase “comprising”. For example, the structure recited in the claims can comprise additional, unrecited elements. However, this renders the claims unclear because the claims recite “having SEQ ID NO: XX” followed by limitations within parentheticals. It is not clear if the language recited in the parentheses is limiting, or if it is only exemplary (i.e., the CDR sequences are limited to the sequences recited in the parentheses or can comprise additional amino acids).
Maintained Rejections
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.
Roovers et al and Prewett et al
Claims 30, 33, 34, 42, 44, 49, 50, 54, 55, 57, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Roovers et al (Cancer Res (2017) 77 (13_Supplement): 32; previously submitted in the restriction mailed on 04/17/2025) as evidenced by ChEMBL – Petosemtamab (www.ebi.ac.uk/chembl/explore/compound/CHEMBL4297781; accessed online 3/10/2026; previously submitted in the Office action mailed on 03/25/2026), and further in view of Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
With respect to instant claims 30, 42, 44, 49, 50, 54, 55, 57, and 58, Roovers et al disclose of a preclinical evaluation of MCLA-158, a bispecific antibody targeting LGR5 and EGFR, using patient-derived colon carcinoma organoids (see Title). A cohort of 32 genetically and transcriptionally annotated patient-derived colorectal cancer and normal colon organoids were used to functionally characterize responses to antibodies based on morphological changes with high content 3D imaging (see Methods). MCLA-158, an ADCC enhanced common light chain IgG1 bispecific antibody, binds in domain III of EGFR and in the N-Cap/1st LRR of LGR5, both ligand binding regions, however, only EGF binding was blocked by MCLA-158 (see Results). MCLA-158 demonstrated inhibitory activity in 74% of tumor organoids independent of KRAS mutational status but was not active on organoids of the cohort harboring both KRAS and PIK3CA mutations (see Results). MCLA-158 significantly inhibited the growth of the tumor compared to both control and cetuximab treatment (see Results). An initial evaluation of MCLA-158 toxicity in cynomolgus monkeys did not demonstrate any pathological finding after repeated dosing at 25 mg/kg (see Results). MCLA-158 demonstrates superior activity compared to reference antibodies in both in vitro and in vivo tumor organoid based assays regardless of KRAS status and was well tolerated in non-human primates (see Conclusions). While Roovers does not disclose of the sequence structure of MCLA-158, it is known that MCLA-158 comprises the heavy chain variable region MF3755 and MF5816, and a light chain as evidenced by ChEMBL. Thus, the MCLA-158 antibody of Roover comprises the sequences recited in the instant application.
Roovers et al fails to disclose of administering a topoisomerase I inhibitors, however this is remedied by Prewett et al.
With respect to claims 30, 33, and 44, Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract).
Therefore, it would have been prima facie obvious to combine the teachings of Roovers and Prewett to develop the instant invention because Roovers et al disclose that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5 comprising the instant claimed sequences, and demonstrated inhibitory activity in patient-derived colon carcinoma organoids. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Therefore, it would have been prima facie obvious to combine the teachings of Roovers and Prewett to develop the instant invention because Roovers et al disclose that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5, and demonstrated inhibitory activity in patient-derived colon carcinoma organoids. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating colorectal cancer.
While the art does not explicitly indicate administering the antibody prior to irinotecan as recited in claim 34, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages, administration schedules, or treatment periods, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages, administration schedules, and treatment period are akin to the variables discussed in the cited MPEP passage, because said drug dosages, administration schedules, and treatment period are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages, administration schedules, and treatment period, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to administration schedule which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited administration schedule and treatment periods are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the administration schedule/treatment period recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
Throsby et al and Prewett et al
Claims 30, 33, 34, 42, 44, 49, 50, 54, 55, 57, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Throsby et al (WO 2017/069628 A2; publication date: 04/27/2017; previously submitted with the Office Action mailed 08/11/2025), and further in view of Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
In regard to clams 30, 42, 44, 49, 50, 54, 55, 57, and 58, Throsby et al disclose of an antibody (PB10651) comprising a variable domain that binds EGFR and a variable domain that binds LGR5 wherein the VH chain of the variable domain that binds EGFR comprises the amino acid sequence of VH chain MF3755 and wherein the VH chain of the variable domain that binds LGR5 comprises the amino acid sequence of VH chain MF5816 (see pg. 44, lines 1-14). Throsby et al teach that the antibodies comprise of a common light chain wherein the common light chain comprises the human kappa light chain IgVĸ1-39*01/IGJĸ1*01 or a fragment or a functional equivalent thereof (see pg. 22, lines 1-30; pg. 57, lines 16-27). Throsby et al found that MF5816 combined with MF3755 in PB10651 adds another level of tumor inhibition by potently reducing tumoroid growth and development, observable by further loss of lumen formation, cell shrinkage and rounding up of the nuclei (see pg. 137, lines 28-31). Specifically, Throsby et al demonstrated that afucosylated PB10651 showed potent inhibitory effects at 10µg/mL test dose in 75% of the 24 different colon tumoroid models; 67% of the wells treated with PB10651 at 10µg/mL showed more than 50% growth reduction; 52% showed more than 50% growth reduction upon PB10651 treatment at 2µg/mL; and PB10651 outperformed cetuximab and the EGFR/TT reference antibody PB9919 (see pg. 138, lines 9-15; pg. 146, lines 4-20). Additionally, Figure 28A shows that treatment with a mixture of anti-LGR5 and anti-EGFR antibodies results in a less potent growth inhibition of tumoroids compared to treatment with the bispecific antibody PB10651 (see pg. 147, lines 1-12). Lastly, Throsby et al teach that the afucosylated PB10651, also referred to as MV1622, displayed significantly increased ADCC activity for all cell lines in combination with the high (V158) and low (F158) FcγRIIIa receptor variant (see pg. 150, lines 17-20). In colorectal patients, MV1622 presented strong tumoristatic activity (see Example 7).
However, Throsby et al fail to disclose of administering a topoisomerase I inhibitor. This is remedied by Prewett et al.
With respect to claims 30, 33, and 44, Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract).
Therefore, it would have been prima facie obvious to combine the teachings of Throsby and Prewett to develop the instant invention because Throsby et al disclose that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5, and demonstrated inhibitory activity in patient-derived colon and colorectal tumoroids. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating colorectal cancer.
While the art does not explicitly indicate administering the antibody prior to irinotecan as recited in claim 34, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages, administration schedules, or treatment periods, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages, administration schedules, and treatment period are akin to the variables discussed in the cited MPEP passage, because said drug dosages, administration schedules, and treatment period are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages, administration schedules, and treatment period, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to administration schedule which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited administration schedule and treatment periods are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the administration schedule/treatment period recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
Applicant’s Arguments
Applicant respectfully traverses the 103 rejections (see pages 12-15 of the Remarks filed 06/25/2026).
Applicant respectfully asserts that the rejections do not establish a prima facie case of obviousness because the Office has not identified a persuasive reason why a person of ordinary skill in the art (POSA) would have been motivated to combine the cited teachings in the manner required by the claims, nor has the Office established that such a person would have had a reasonable expectation of successfully treating colorectal cancer using the claimed combination of a structurally defined EGFR/LGR5 bispecific antibody and irinotecan.
The rejection further fails because the cited art does not provide any rationale for selecting irinotecan in particular, as opposed to the numerous other chemotherapeutic and targeted agents available to a skilled artisan at the time. The Office relies on Prewett's disclosure of a specific combination of IMC-C225 with irinotecan but does not explain why a POSA would have selected irinotecan from among the wide array of known anticancer therapies when attempting to combine a different, structurally distinct EGFR/LGRS bispecific antibody with a second agent. In the absence of such a rationale, the rejection impermissibly assumes that any known chemotherapeutic agent could be substituted into the claimed method with a reasonable expectation of success… The Office's analysis instead rests on the generalization that because irinotecan was reported to enhance the activity of one specific anti-EGFR antibody (IMC-C225) in Prewett, irinotecan would have been an obvious and interchangeable partner for any EGFR-targeting antibody, including the structurally distinct bispecific antibody recited in the claims. That reasoning is legally deficient. Indeed, even if Prewett were interpreted as directing a skilled artisan toward combining an EGFR-targeting antibody with irinotecan, that teaching is limited to the specific context of IMC- C225. Prewett does not suggest that irinotecan is broadly preferred across all antibodies, much less bispecific antibodies, and does not provide any guidance regarding how a bispecific EGFR/LGR5 antibody would behave in combination with irinotecan. Thus, Prewett at most provides a single data point, not a generalizable rule. The Federal Circuit has cautioned against precisely this type of overgeneralization. In Sanofi, the court rejected the notion that success of some members of a class renders all members obvious to try, particularly where the art provides no guidance toward the claimed selection. Id. at 1360. Nor has the Office established a reasonable expectation that irinotecan, specifically, would function in the claimed combination. The requirement of a reasonable expectation of success is separate from, and in addition to, any alleged motivation to combine. Even if a skilled artisan had contemplated pairing an antibody with a chemotherapeutic agent, the art provides no basis to expect that irinotecan could be successfully used with the claimed EGFR/LGR5 bispecific antibody in colorectal cancer treatment. This is particularly true where the claimed antibody differs fundamentally from the antibody studied in Prewett, including by virtue of its bispecificity and LGR5 targeting. The rejection's reliance on substitution reasoning is therefore improper. As the Federal Circuit has explained, obviousness cannot be established by using the claimed invention as a blueprint and selectively combining prior-art teachings to match it. See, ATD Corp. v. Lydall, Inc., 159 F.3d 534 (Fed. Cir. 1998); see also Orthopedic Equip. Co. v. United States, 702 F.2d 1005 (Fed. Cir. 1983). Here, the Office has effectively started with Applicant's disclosure - specifically the pairing of the claimed bispecific antibody with irinotecan - and then located separate references disclosing (i) the antibody and (ii) irinotecan combination therapy in a different context. That reconstruction reflects hindsight, not the perspective of a skilled artisan at the time of the invention.
Response to Arguments
Applicant's arguments filed 06/25/2026 have been fully considered but they are not persuasive.
Examiner respectfully disagrees with Applicant’s assertion that the rejections do not establish a prima facie case of obviousness because the Office has not identified a persuasive reason why a person of ordinary skill in the art (POSA) would have been motivated to combine the cited teachings in the manner required by the claims, nor has the Office established that such a person would have had a reasonable expectation of successfully treating colorectal cancer using the claimed combination of a structurally defined EGFR/LGR5 bispecific antibody and irinotecan. As stated in the rejections, Roovers and Throsby teach of the claimed bispecific antibody and its efficacy in treating colorectal cancer; and, Prewett teaches that administering irinotecan not only treated colorectal cancer, but enhanced the efficacy of the anti-EGFR antibody when co-administered. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients. Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering the claimed bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating colorectal cancer.
With respect to Applicant’s arguments that the rejection further fails because the cited art does not provide any rationale for selecting irinotecan in particular as opposed to the numerous other chemotherapeutic and targeted agents available to a skilled artisan at the time, Examiner respectfully disagrees. Prewett teaches that administering irinotecan not only treated colorectal cancer, but enhanced the efficacy of the anti-EGFR antibody when co-administered. This teaching provides sufficient correlation between the art and the present invention as Prewett provides an anti-EGFR antibody and irinotecan as a method of treating colorectal cancer. Additionally, it was known in the art that irinotecan is a key chemotherapeutic drug for metastatic colorectal cancer (see Fujita et al, World J Gastroenterol 2015 November 21; 21(43): 12234-12248; and, Kobayashi et al, STEM CELLS 2012;30:2631–2644) thus it would have been obvious for one to select irinotecan as a method of treating colorectal cancer opposed to other various anticancer therapies. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Further, Applicant is reminded that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Prewett may not teach of the claimed bispecific antibody, but Roovers and Throsby do and that the antibody is effective in treating colorectal cancer. Thus, taken altogether, one would have a reasonable expectation that administering the claimed antibody with irinotecan would treat colorectal cancer as claimed.
As such, the 103 rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
11,939,394
Claims 30, 33, 34, 44, 49, 50, 54, 55, 57, and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,939,394 B2 in view of Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
The ‘394 patent is drawn to bispecific antibodies that comprise a variable domain that binds an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5 (see claims 1 and 7-30). Particularly, the ‘394 patent discloses of a bispecific antibody that comprises SEQ ID NO: 20 and SEQ ID NO: 26 (see claims 12 and 26) which shares 100% identity with instant SEQ ID NO: 89 and 107, respectively; and, consequently comprises the EGFR CDR sequences of SEQ ID Nos: 17, 19, and 21 and LGR5 CDR sequences of SEQ ID Nos: 69, 71, and 73. Additionally, the ‘394 patent discloses that the bispecific antibodies comprise a light chain variable domain comprising SEQ ID NO: 80 (see claim 2) which shares 100% identity with instant SEQ ID NO: 113.
The difference between the instant claims and the ‘394 patent is that the instant claims is drawn to a method of using a product whereas the ’394 patent is drawn to the product. However, the Federal Circuit has held that obviousness-type double patenting exists for method claims that simply claim the disclosed use of a composition in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). The instant application and the copending application are not divisional applications resulting from restriction, and therefore no protection under the provisions of 35 USC 121. The ‘394 patent discloses of utilizing the claimed bispecific antibodies to treat colorectal patients (see Example 7).
Furthermore, with respect to administering irinotecan, Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract). Therefore, it would have been prima facie obvious to combine the teachings of the ‘394 patent and Prewett to develop the instant invention because the ‘394 patent discloses that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5, and demonstrated inhibitory activity in patient-derived colon and colorectal tumoroids. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating colorectal cancer.
While the art does not explicitly indicate administering the antibody prior to irinotecan as recited in claim 34, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages, administration schedules, or treatment periods, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages, administration schedules, and treatment period are akin to the variables discussed in the cited MPEP passage, because said drug dosages, administration schedules, and treatment period are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages, administration schedules, and treatment period, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to administration schedule which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited administration schedule and treatment periods are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the administration schedule/treatment period recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
17/921,042
Claims 30, 33, 34, 42, 44, 49, 50, 54, 55, 57 and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31, 34, 37, 38, 43-44, and 47 of copending Application No. 17/921,042 in view of Throsby et al (WO 2017/069628 A2; publication date: 04/27/2017; previously submitted with the Office Action mailed 08/11/2025) and Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
With respect to instant claims 30, 42, 44, 49, 50, 54, 55, 57, and 58, the ‘042 claims are drawn to a method of treating a cancer comprising administering to a human subject in need thereof a flat dose of 1500 mg of a bispecific antibody that comprises a first antigen- binding site that specifically binds an extracellular part of epidermal growth factor receptor (EGFR) and a second antigen-binding site that specifically binds leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5); wherein said first antigen-binding site comprises at least the complementarity determining region (CDR)1, CDR2, and CDR3 sequences of the heavy chain variable region MF3755 (SEQ ID NO: 4) wherein said second antigen-binding site comprises at least the CDR1, CDR2, and CDR3 sequences of the heavy chain variable region MF5816 (SEQ ID NO: 13); and wherein the bispecific antibody comprises the CDR1, CDR2, and CDR3 sequences of a common light chain comprising SEQ ID NO: 122 (see claims 31 and 47). The ‘042 claims are drawn to the method of claim 31, wherein the antibody is ADCC enhanced (see claim 43). Lastly, the ‘042 claims are drawn to the method of claim 31, wherein the antibody is afucosylated (see claim 44).
The difference between the instant claims and the ‘042 claims is that the instant claims are drawn to a method of treating cancer wherein the method comprises administering a bispecific antibody and irinotecan. Additionally, the instant application discloses the bispecific antibody comprises a common light chain. This is remedied by Throsby and Prewett.
With respect to the common light chain, Throsby et al disclose of an antibody (PB10651) comprising a variable domain that binds EGFR and a variable domain that binds LGR5 wherein the VH chain of the variable domain that binds EGFR comprises the amino acid sequence of VH chain MF3755 and wherein the VH chain of the variable domain that binds LGR5 comprises the amino acid sequence of VH chain MF5816 (see pg. 44, lines 1-14). Throsby et al teach that the antibodies comprise of a common light chain wherein the common light chain comprises the human kappa light chain IgVĸ1-39*01/IGJĸ1*01 or a fragment or a functional equivalent thereof (see pg. 22, lines 1-30; pg. 57, lines 16-27). Throsby et al found that MF5816 combined with MF3755 in PB10651 adds another level of tumor inhibition by potently reducing tumoroid growth and development, observable by further loss of lumen formation, cell shrinkage and rounding up of the nuclei (see pg. 137, lines 28-31). Specifically, Throsby et al demonstrated that afucosylated PB10651 showed potent inhibitory effects at 10µg/mL test dose in 75% of the 24 different colon tumoroid models; 67% of the wells treated with PB10651 at 10µg/mL showed more than 50% growth reduction; 52% showed more than 50% growth reduction upon PB10651 treatment at 2µg/mL; and PB10651 outperformed cetuximab and the EGFR/TT reference antibody PB9919 (see pg. 138, lines 9-15; pg. 146, lines 4-20). Additionally, Figure 28A shows that treatment with a mixture of anti-LGR5 and anti-EGFR antibodies results in a less potent growth inhibition of tumoroids compared to treatment with the bispecific antibody PB10651 (see pg. 147, lines 1-12). Lastly, Throsby et al teach that the afucosylated PB10651, also referred to as MV1622, displayed significantly increased ADCC activity for all cell lines in combination with the high (V158) and low (F158) FcγRIIIa receptor variant (see pg. 150, lines 17-20). In colorectal patients, MV1622 presented strong tumoristatic activity (see Example 7).
Further, with respect to administering irinotecan, Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract). Therefore, it would have been prima facie obvious to combine the teachings of the ‘042 application, Throsby, and Prewett to develop the instant invention because Throsby et al disclose that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5, and demonstrated inhibitory activity in patient-derived colon and colorectal tumoroids. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating cancer.
While the art does not explicitly indicate administering the antibody prior to irinotecan as recited in claim 34, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages, administration schedules, or treatment periods, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages, administration schedules, and treatment period are akin to the variables discussed in the cited MPEP passage, because said drug dosages, administration schedules, and treatment period are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages, administration schedules, and treatment period, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to administration schedule which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited administration schedule and treatment periods are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the administration schedule/treatment period recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
This is a provisional nonstatutory double patenting rejection.
18/257,528
Claims 44, 50, 55, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-28 and 30-33 of copending Application No. 18/257,528 in view of Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
With respect to instant claims 44, 50, 55, and 58, the ‘528 claims are drawn to a method of treating head and neck cancer in a subject in need thereof, comprising administering to the subject an antibody or antigen-binding fragment thereof comprising a variable domain that binds an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5,wherein the subject is administered a flat dose of 1500 mg of the antibody or an equivalent amount of the antigen-binding fragment thereof, wherein the variable domain that binds an extracellular part of EGFR comprises a heavy chain variable region comprising the CDR1, CDR2 and CDR3 sequences of a variable region selected from the group consisting of MF3370 (SEQ ID NO: 3); MF3755 (SEQ ID NO: 4); MF4280 (SEQ ID NO: 5) or MF4289 (SEQ ID NO: 6), wherein the variable domain that binds an extracellular part of LGR5 comprises a heavy chain variable region comprising the CDR1, CDR2 and CDR3 sequences of a variable region selected from the group consisting of MF5790 (SEQ ID NO: 7); MF5803 (SEQ ID NO: 8); MF5805 (SEQ ID NO: 9); MF5808 (SEQ ID NO: 10); MF5809 (SEQ ID NO: 11); MF5814 (SEQ ID NO: 12); MF5816 (SEQ ID NO: 13); MF5817 (SEQ ID NO: 14); or MF5818 (SEQ ID NO: 15) and, wherein both variable domains comprise CDR1, CDR2 and CDR3 regions of the light chain variable region of SEQ ID NO: 122 (see claims 20-31). SEQ ID Nos: 4, 13, and 122 share 100% identity with instant SEQ ID Nos: 89, 107, and 133, respectively. Additionally, the ‘528 claims are drawn to the method of claim 20, wherein the antibody is ADCC enhanced (see claim 32). Lastly, the ‘528 claims are drawn to the method of claim 20, wherein the antibody is afucosylated (see claim 33).
The difference between the instant claims and the ‘528 application is that the instant claims are drawn to a method of inhibiting proliferation of a cell wherein the method comprises administering the claimed bispecific antibody and irinotecan.
However, Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract). Therefore, it would have been prima facie obvious to combine the teachings of the ‘528 application and Prewett to develop the instant invention because the ‘528 application discloses that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for inhibiting proliferation of a cell.
This is a provisional nonstatutory double patenting rejection.
18/431,642
Claims 30, 33, 34, 42, 44, 49, 50, 54, 55, 57 and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-55, 57, and 58 of copending Application No. 18/431,642 in view of Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
The ‘642 claims are drawn to a method for the treatment of an individual that has a cancer, specifically colorectal cancer, the method comprising administering a bispecific antibody to said individual, wherein said bispecific antibodies that comprise a variable domain that binds an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5 (see claims 29-55, 57, and 58). Particularly, the ‘642 claims disclose of a bispecific antibody that comprises SEQ ID NO: 20 and SEQ ID NO: 26 (see claims 37 and 49) which shares 100% identity with instant SEQ ID NO: 89 and 107, respectively; and, consequently comprises the EGFR CDR sequences of SEQ ID Nos: 17, 19, and 21 and LGR5 CDR sequences of SEQ ID Nos: 69, 71, and 73. Additionally, the ‘642 claims disclose that the bispecific antibodies comprise a light chain variable domain comprising SEQ ID NO: 80 (see claim 31) which shares 100% identity with instant SEQ ID NO: 113.
The difference between the instant claims and the ‘642 application is that the instant claims is drawn to a method of treating cancer comprising administering irinotecan and the bispecific antibody. However, this is remedied by Prewett et al.
Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract). Therefore, it would have been prima facie obvious to combine the teachings of the ‘642 application and Prewett to develop the instant invention because the ‘642 application discloses of a method of treating cancer comprising administering the claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating colorectal cancer.
While the art does not explicitly indicate administering the antibody prior to irinotecan as recited in claim 34, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages, administration schedules, or treatment periods, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages, administration schedules, and treatment period are akin to the variables discussed in the cited MPEP passage, because said drug dosages, administration schedules, and treatment period are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages, administration schedules, and treatment period, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to administration schedule which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited administration schedule and treatment periods are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the administration schedule/treatment period recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
This is a provisional nonstatutory double patenting rejection.
18/694,252
Claims 30, 33, 34, 42, 44, 49, 50, 54, 55, 57, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 10, 16, 18, 20, 27, 31, 36-40, and 42 of copending Application No. 18/694,252 in view of Prewett et al (Clin Cancer Res 2002;8:994-1003; previously submitted in the restriction mailed on 04/17/2025).
The ‘252 claims are drawn to a method of treating a subject having an EGFR expressing cancer, wherein said subject has progressed after having received prior treatment with an immune checkpoint inhibitor, the method comprising providing the subject with an effective amount of an antibody or functional part thereof that comprises a first variable domain that binds an extracellular part of EGFR comprising a heavy chain variable region that comprises the CDR1, CDR2 and CDR3 sequences of MF3755 (SEQ ID NO:4) and a second variable domain comprising a heavy chain variable region that comprises the CDR1, CDR2 and CDR3 sequences of MF5816 (SEQ ID NO:13) (see claims 3, 10, 16, 18, 20, 27, and 31). SEQ ID Nos: 4 and 13 share 100% identity with instant SEQ ID Nos: 89 and 107, respectively. Additionally, the ‘252 claims are drawn to the method of claim 3, wherein the first and second variable domains comprise a light chain variable region comprising the LCDR1 amino acid sequence QSISSY, the LCDR2 amino acid sequence AAS, and the LCDR3 amino acid sequence QQSYSTPPT (see claim 37). The ‘252 claims are drawn to the method of claim 37, wherein the first and second variable domains comprise a light chain variable region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 122 (see claims 38-40). SEQ ID NO: 122 shares 100% identity with instant SEQ ID NO: 113.
The difference between the instant claims and the ‘252 application is that the instant claims are drawn to a method of treating cancer wherein the method comprises administering irinotecan and the bispecific antibody. This is remedied by Prewett.
Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract). Therefore, it would have been prima facie obvious to combine the teachings of the ‘252 application and Prewett to develop the instant invention because the ‘252 application discloses of a method of treating cancer comprising administering the claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within cancer patients.
Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by administering a bispecific antibody that targets EGFR and LGR5 in combination with irinotecan as taught in the references above, one would achieve a method for treating cancer.
While the art does not explicitly indicate administering the antibody prior to irinotecan as recited in claim 34, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages, administration schedules, or treatment periods, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages, administration schedules, and treatment period are akin to the variables discussed in the cited MPEP passage, because said drug dosages, administration schedules, and treatment period are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages, administration schedules, and treatment period, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to administration schedule which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited administration schedule and treatment periods are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the administration schedule/treatment period recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
This is a provisional nonstatutory double patenting rejection.
Applicant’s Arguments
Applicant traverses the double patenting rejections (see pages 15 and 16 of the Remarks filed 06/25/2026).
As described above, the pending claims are directed to treatment of colorectal cancer with the combination of the claimed bispecific antibody and irinotecan. For the same reasons set forth above, the pending claims are patentably distinct from the claims of U.S. Patent No. 11,939,394 in view of Prewett et al., as well as the above-cited provisional rejections. Therefore, Applicant respectfully requests that this rejection be reconsidered and withdrawn. Moreover, Applicant respectfully asserts that the above-described amendments, remarks, and arguments overcome all of the outstanding objections and rejections such that all that remains are the provisional rejections under obviousness-type double patenting. Accordingly, Applicant respectfully requests that the provisional rejection be withdrawn so that the claimed invention can proceed to allowance under M.P.E.P. 804(I)(B)(1)(b).
Response to Arguments
Applicant's arguments filed 06/25/2026 have been fully considered but they are not persuasive.
As stated above, the Federal Circuit has held that obviousness-type double patenting exists for method claims that simply claim the disclosed use of a composition in the specification. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). The instant application and the copending application are not divisional applications resulting from restriction, and therefore no protection under the provisions of 35 USC 121. The ‘394 patent discloses of utilizing the claimed bispecific antibodies to treat colorectal patients (see Example 7). Further, Prewett et al disclose that anti-EGFR antibody IMC-C225 can inhibit the growth of human colon carcinoma tumor cells in vitro and xenografts of these in athymic mice (see Abstract). Prewett et al demonstrated the in vivo activity of IMC-C225 combined with the topoisomerase I inhibitor irinotecan (CPT-11) using two models of human colorectal carcinoma in nude mice resulted in significantly inhibited growth of established DLD-1 and HT-29 tumors compared with either CPT-11 or IMC-C225 monotherapy (see Abstract). Therefore, it would have been prima facie obvious to combine the teachings of the ‘394 patent and Prewett to develop the instant invention because the ‘394 patent discloses that their claimed bispecific antibody binds to an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5, and demonstrated inhibitory activity in patient-derived colon and colorectal tumoroids. Further, Prewett et al disclose that the antitumor activity of anti-EGFR antibodies is enhanced with the addition of a topoisomerase I inhibitor such as irinotecan. Thus, there is a reasonable expectation that administering the bispecific antibody and irinotecan would enhance the therapeutic activity within colorectal cancer patients.
As such, the double patenting rejections are maintained.
Conclusion
No claims are allowed.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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