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 .
DETAILED ACTION
Applicant’s election without traverse of anti-VEGF/VEGFR therapy as a type of prior treatment in the reply filed on 12/05/2025 is acknowledged.
Claims 1-26 are pending.
Claims 20-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/05/2025.
Claims 1-19, 25, and 26 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-19, 25, and 26 have an effective filing date of 05/05/2022, corresponding to PRO 63/338,807.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/11/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections
35 U.S.C. 102(a)(1)
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-10, 13-16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017).
At columns 4 and 5, Chiu et al. disclose an “isolated bispecific EGFR/c-Met antibody, comprising: combining an isolated monospecific bivalent anti-EGFR antibody comprising two heavy chains of SEQ ID NO: 199 and two light chains of SEQ ID NO: 200 and an isolated monospecific bivalent anti-c-Met antibody comprising two heavy chains of SEQ ID NO: 201 and two light chains of SEQ ID NO: 202 in a mixture of about 1:1 molar ratio; introducing a reducing agent into the mixture; incubating the mixture about ninety minutes to about six hours; removing the reducing agent; and purifying the bispecific EGFR/c-Met antibody that comprises a first heavy chain of SEQ ID NO: 199 and a second heavy chain of SEQ ID NO: 201, a first light chain of SEQ ID NO: 200 and a second light chain of SEQ ID NO: 202, wherein the first heavy chain of SEQ ID NO: 199 pairs with the first light chain of SEQ ID NO: 200 to form the first binding domain that specifically binds EGFR, and the second heavy chain of SEQ ID NO: 201 pairs with the second light chain of SEQ ID NO: 202 to form the second binding domain that specifically binds c-Met.”
SEQ ID NO: 199 of Chiu et al. is an anti-EGFR heavy chain that shares 100% sequence homology with the instant SEQ ID NO: 17, which comprises the heavy chain variable region (VH) of the instant SEQ ID NO: 13, which comprises the complementarity determining regions (CDRs) of SEQ ID NO(s): 1-3.
SEQ ID NO: 200 of Chiu et al. is an anti-EGFR light chain that shares 100% sequence homology with the instant SEQ ID NO: 18, which comprises the light chain variable region (VL) of the instant SEQ ID NO: 14, which comprises the CDRs of SEQ ID NO(s): 4-6.
SEQ ID NO: 201 of Chiu et al. is an anti-c-Met heavy chain that shares 100% sequence homology with the instant SEQ ID NO: 19, which comprises the heavy chain variable region (VH) of the instant SEQ ID NO: 15, which comprises the CDRs of SEQ ID NO(s): 7-9.
SEQ ID NO: 202 of Chiu et al. is an anti-c-Met light chain that shares 100% sequence homology with the instant SEQ ID NO: 20, which comprises the heavy chain variable region (VH) of the instant SEQ ID NO: 16, which comprises the CDRs of SEQ ID NO(s): 10-12.
At column 53, Chiu et al. disclose that “[e]xemplary cancers that are amenable to treatment by the bispecific molecules of the invention such as the bispecific EGFR/c-Met antibodies of the invention include epithelial cell cancers, breast cancer, ovarian cancer, lung cancer, non-small cell lung cancer (NSCLC), lung adenocarcinoma, small cell lung cancer, colorectal cancer, anal cancer, prostate cancer, kidney cancer, bladder cancer, head and neck cancer, pharynx cancer, cancer of the nose, pancreatic cancer, skin cancer, oral cancer, cancer of the tongue, esophageal cancer, vaginal cancer, cervical cancer, cancer of the spleen, testicular cancer, gastric cancer, cancer of the thymus, colon cancer, thyroid cancer, liver cancer (hepatocellular carcinoma (HCC)) or sporadic or hereditary papillary renal cell carcinoma (PRCC) (emphasis added).”
Therefore Chiu discloses a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202. SEQ ID NO: 199 of Chiu et al. is an anti-EGFR heavy chain that shares 100% sequence homology with the instant SEQ ID NO: 17, which comprises the heavy chain variable region (VH) of the instant SEQ ID NO: 13, which comprises the complementarity determining regions (CDRs) of SEQ ID NO(s): 1-3. SEQ ID NO: 200 of Chiu et al. is an anti-EGFR light chain that shares 100% sequence homology with the instant SEQ ID NO: 18, which comprises the light chain variable region (VL) of the instant SEQ ID NO: 14, which comprises the CDRs of SEQ ID NO(s): 4-6. SEQ ID NO: 201 of Chiu et al. is an anti-c-Met heavy chain that shares 100% sequence homology with the instant SEQ ID NO: 19, which comprises the heavy chain variable region (VH) of the instant SEQ ID NO: 15, which comprises the CDRs of SEQ ID NO(s): 7-9. SEQ ID NO: 202 of Chiu et al. is an anti-c-Met light chain that shares 100% sequence homology with the instant SEQ ID NO: 20, which comprises the heavy chain variable region (VH) of the instant SEQ ID NO: 16, which comprises the CDRs of SEQ ID NO(s): 10-12. The invention of Chiu et al. meets the limitations of claims 1-4 and 6.
With respect to claim 5, at column 42, Chiu et al. disclose that bispecific antibodies of the invention may comprise heavy chains of the IgG1 isotype.
With respect to claim 7, at column 49, Chiu et al. disclose that “[i]n some embodiments described herein, the bispecific EGFR/c-Met antibody of the invention has a biantennary glycan structure with fucose content of about between 1% to about 15%...”
With respect to claim 8-10, at column 58, Chiu et al. disclose that the bispecific EGFR/c-Met antibody of the invention may be administered intravenously at a dosage of 500 mg or 1000 mg.
With respect to claims 13 and 14, at column 58, Chiu et al. disclose that “[t]he bispecific EGFR/c-Met antibodies of the invention may be administered to a patient by any suitable route, for example parentally by intravenous (IV) infusion or bolus injection, intramuscularly or subcutaneously or intraperitoneally. IV infusion can be given over as little as 15 minutes, but more often for 30 minutes, 60 minutes, 90 minutes or even 2 or 3 hours. The bispecific EGFR/c-Met antibodies of the invention may also be injected directly into the site of disease (e.g., the tumor itself). The dose given to a patient having a cancer is sufficient to alleviate or at least partially arrest the disease being treated (“therapeutically effective amount”)…”
With respect to claims 15 and 16, at column 59, Chiu et al. disclose that “[a]dministration of the bispecific EGFR/c-Met antibody of the invention may be repeated after one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, one month, five weeks, six weeks, seven weeks, two months, three months, four months, five months, six months or longer.”
With respect to claim 18, at column 54, Chiu et al. disclose that “[i]n some methods described herein, the antibodies of the invention may be used to treat a subject having cancer that is resistant or has acquired resistance to treatment with one or more EGFR inhibitors.”
Therefore the disclosure of Chiu et al. meets the limitations of claims 1-10, 13-16, and 18.
35 U.S.C. 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-18 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017).
As indicated above the disclosure of Chiu et al. meets the limitations of claims 1-10, 13-16, and 18.
Claims 11 and 12 recite dosages of the claimed bispecific EGFR/c-Met antibody, and claim 17 encompasses administration schedules for the claimed bispecific EGFR/c-Met antibody. With respect to these antibody dosages and administration schedules, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation, which states that:
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, antibody dosages and administration schedules, 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 antibody dosages and administration schedules are akin to the variables discussed in the cited MPEP passage, because antibody dosages and administration schedules are optimizable variables that would affect at least efficacy and safety. 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 antibody dosages and administration schedules, because such optimization would produce a more effective/safer 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, claims 11, 12, and 17 are drawn to antibody dosages and administration schedules, and these variables achieve a recognized result, such as drug efficacy and/or drug toxicity. Accordingly the recited antibody dosages and administration schedules are result-effective variables that achieve a recognized result, such as drug efficacy and/or drug toxicity, and it is submitted that since one of ordinary skill in the art would have been motivated to determine the optimum or workable ranges of said variables, the recited antibody dosages and administration schedules were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
With respect to claim 26, one of ordinary skill in the art would have had a reasonable expectation that the invention of Chiu et al. is effective in treating liver cancer. One of ordinary skill in the art would also appreciate that the invention of Chiu et al. would provide a therapeutic benefit to individuals that are treatment naïve, as well as 1) patients who have either not responded to prior treatment or 2) patients who have relapsed following prior treatment.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claims 19 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017), as applied to claims 1-18 and 26, and further in view of Wang et al. (Exp Hematol Oncol, 10(45): 1-5, 2021).
As indicated above Chiu et al. teach a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202. Chiu et al. do not teach or suggest a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, wherein said subject has received a prior treatment of anti-VEGF/VEGFR therapy (bevacizumab). This deficiency is remedied by Wang et al.
At p. 1 and 2, Wang et al. teach that a patient with unresectable HCC was treated with atezolizumab/bevacizumab therapy but progressed after 40 weeks - “after 40 weeks of atezo/bev, follow-up computed tomography (CT) scans revealed progression of the huge tumor.” Based upon the teachings of Wang et al., one of ordinary skill in the art would appreciate that some HCC patients who are treated with atezolizumab/bevacizumab therapy will progress following treatment, and these patients will be in need of other treatments to address said cancer progression.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Chiu et al., with those of Wang et al. to arrive at a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202, wherein said subject has received a prior treatment of anti-VEGF/VEGFR therapy (bevacizumab). One of ordinary skill in the art would have been motivated to do so, because Chiu et al. teach a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202. Further based upon the teachings of Wang et al., one of ordinary skill in the art would appreciate that some HCC patients who are treated with atezolizumab/bevacizumab therapy will progress following treatment, and these patients will be in need of other treatments to address said cancer progression. One of ordinary skill in the art would have had ample motivation to administer the treatment method of Chiu et al. to HCC patients who have progressed following atezolizumab/bevacizumab therapy, because there would have been a reasonable expectation that the treatment method of Chiu et al. would provide a therapeutic benefit to HCC patients who have progressed following atezolizumab/bevacizumab therapy.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Nonstatutory 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.
Claims 1-18 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claim 1 of U.S. Patent No. 9,593,164 and 2) claim 1 of U.S. Patent 9,695,242 in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017).
The conflicting claims recite a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20).
The teachings of Chiu et al. are disclosed above.
One of ordinary skill in the art would have been motivated to modify the conflicting claims to recite a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20). One of ordinary skill in the art would have been motivated to do so, because in view of the teachings of Chiu et al., there would have been a reasonable expectation that the bispecific EGFR/c-Met antibody of the instant claims would provide a therapeutic benefit to liver cancer (HCC) patients. The invention of the conflicting claims and Chiu et al. meets the limitations of claims 1-4 and 6.
With respect to claim 5, at column 42, Chiu et al. disclose that bispecific antibodies of the invention may comprise heavy chains of the IgG1 isotype.
With respect to claim 7, at column 49, Chiu et al. disclose that “[i]n some embodiments described herein, the bispecific EGFR/c-Met antibody of the invention has a biantennary glycan structure with fucose content of about between 1% to about 15%...”
With respect to claim 8-10, at column 58, Chiu et al. disclose that the bispecific EGFR/c-Met antibody of the invention may be administered intravenously at a dosage of 500 mg or 1000 mg.
Claims 11, 12, and 17 are drawn to antibody dosages and administration schedules, and these variables achieve a recognized result, such as drug efficacy and/or drug toxicity. Accordingly the recited antibody dosages and administration schedules are result-effective variables that achieve a recognized result, such as drug efficacy and/or drug toxicity, and it is submitted that since one of ordinary skill in the art would have been motivated to determine the optimum or workable ranges of said variables, the recited antibody dosages and administration schedules were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
With respect to claims 13 and 14, at column 58, Chiu et al. disclose that “[t]he bispecific EGFR/c-Met antibodies of the invention may be administered to a patient by any suitable route, for example parentally by intravenous (IV) infusion or bolus injection, intramuscularly or subcutaneously or intraperitoneally. IV infusion can be given over as little as 15 minutes, but more often for 30 minutes, 60 minutes, 90 minutes or even 2 or 3 hours. The bispecific EGFR/c-Met antibodies of the invention may also be injected directly into the site of disease (e.g., the tumor itself). The dose given to a patient having a cancer is sufficient to alleviate or at least partially arrest the disease being treated (“therapeutically effective amount”)…”
With respect to claims 15 and 16, at column 59, Chiu et al. disclose that “[a]dministration of the bispecific EGFR/c-Met antibody of the invention may be repeated after one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, one month, five weeks, six weeks, seven weeks, two months, three months, four months, five months, six months or longer.”
With respect to claim 18, at column 54, Chiu et al. disclose that “[i]n some methods described herein, the antibodies of the invention may be used to treat a subject having cancer that is resistant or has acquired resistance to treatment with one or more EGFR inhibitors.”
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al.
Claims 19 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claim 1 of U.S. Patent No. 9,593,164 and 2) claim 1 of U.S. Patent 9,695,242 in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017), as applied to claims 1-18 and 26, and further in view of Wang et al. (Exp Hematol Oncol, 10(45): 1-5, 2021).
The teachings of Wang et al. are detailed above.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of the conflicting claims and Chiu et al. with those of Wang et al. to arrive at a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20), wherein said subject has received a prior treatment of anti-VEGF/VEGFR therapy (bevacizumab). One of ordinary skill in the art would have been motivated to do so, because the conflicting claims and Chiu et al. teach a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20). Further based upon the teachings of Wang et al., one of ordinary skill in the art would appreciate that some HCC patients who are treated with atezolizumab/bevacizumab therapy will progress following treatment, and these patients will be in need of other treatments to address said cancer progression. One of ordinary skill in the art would have had ample motivation to administer the treatment method of the conflicting claims and Chiu et al. to HCC patients who have progressed following atezolizumab/bevacizumab therapy, because there would have been a reasonable expectation that the treatment method of the conflicting claims and Chiu et al. would provide a therapeutic benefit to HCC patients who have progressed following atezolizumab/bevacizumab therapy.
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al. and Wang et al.
Claims 1-4 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 9,580,508.
Although the claims at issue are not identical, they are not patentably distinct from each other, because both sets of claims encompass a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20).
Claims 5, 7-18, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 9,580,508, as applied to claims 1-4 and 6, and further in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017).
The teachings of Chiu et al. are disclosed above. It would have been prima facie obvious to modify the conflicting claims to include the bispecific EGFR/c-Met antibody characteristics recited in the following claims, because the resultant invention would be expected to provide a therapeutic benefit to HCC patients.
With respect to claim 5, at column 42, Chiu et al. disclose that bispecific antibodies of the invention may comprise heavy chains of the IgG1 isotype.
With respect to claim 7, at column 49, Chiu et al. disclose that “[i]n some embodiments described herein, the bispecific EGFR/c-Met antibody of the invention has a biantennary glycan structure with fucose content of about between 1% to about 15%...”
With respect to claim 8-10, at column 58, Chiu et al. disclose that the bispecific EGFR/c-Met antibody of the invention may be administered intravenously at a dosage of 500 mg or 1000 mg.
With respect to claims 13 and 14, at column 58, Chiu et al. disclose that “[t]he bispecific EGFR/c-Met antibodies of the invention may be administered to a patient by any suitable route, for example parentally by intravenous (IV) infusion or bolus injection, intramuscularly or subcutaneously or intraperitoneally. IV infusion can be given over as little as 15 minutes, but more often for 30 minutes, 60 minutes, 90 minutes or even 2 or 3 hours. The bispecific EGFR/c-Met antibodies of the invention may also be injected directly into the site of disease (e.g., the tumor itself). The dose given to a patient having a cancer is sufficient to alleviate or at least partially arrest the disease being treated (“therapeutically effective amount”)…”
With respect to claims 15 and 16, at column 59, Chiu et al. disclose that “[a]dministration of the bispecific EGFR/c-Met antibody of the invention may be repeated after one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, one month, five weeks, six weeks, seven weeks, two months, three months, four months, five months, six months or longer.”
With respect to claim 18, at column 54, Chiu et al. disclose that “[i]n some methods described herein, the antibodies of the invention may be used to treat a subject having cancer that is resistant or has acquired resistance to treatment with one or more EGFR inhibitors.”
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al.
Claims 19 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 9,580,508 and Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017), as applied to claims 1-18 and 26, and further in view of Wang et al. (Exp Hematol Oncol, 10(45): 1-5, 2021).
The teachings of Wang et al. are detailed above.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of the conflicting claims and Chiu et al. with those of Wang et al. to arrive at a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20), wherein said subject has received a prior treatment of anti-VEGF/VEGFR therapy (bevacizumab). One of ordinary skill in the art would have been motivated to do so, because the conflicting claims and Chiu et al. teach a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 199 (shares 100% sequence homology with the instant SEQ ID NO: 17), SEQ ID NO: 200 (shares 100% sequence homology with the instant SEQ ID NO: 18), SEQ ID NO: 201 (shares 100% sequence homology with the instant SEQ ID NO: 19), and SEQ ID NO: 202 (shares 100% sequence homology with the instant SEQ ID NO: 20), wherein the subject has received a prior treatment. Further based upon the teachings of Wang et al., one of ordinary skill in the art would appreciate that some HCC patients who are treated with atezolizumab/bevacizumab therapy will progress following treatment, and these patients will be in need of other treatments to address said cancer progression. One of ordinary skill in the art would have had ample motivation to administer the treatment method of the conflicting claims and Chiu et al. to HCC patients who have progressed following atezolizumab/bevacizumab therapy, because there would have been a reasonable expectation that the treatment method of the conflicting claims and Chiu et al. would provide a therapeutic benefit to HCC patients who have progressed following atezolizumab/bevacizumab therapy.
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al. and Wang et al.
Claims 1 and 2 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11 and 16 of copending Application No. 17/398,294 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other, because both sets of claims encompass a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 5, 7-18, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11 and 16 of copending Application No. 17/398,294 (reference application), as applied to claims 1 and 2, and further in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017).
The teachings of Chiu et al. are disclosed above. It would have been prima facie obvious to modify the conflicting claims to include the bispecific EGFR/c-Met antibody characteristics recited in the following claims, because the resultant invention would be expected to provide a therapeutic benefit to HCC patients.
With respect to claim 5, at column 42, Chiu et al. disclose that bispecific antibodies of the invention may comprise heavy chains of the IgG1 isotype.
With respect to claim 7, at column 49, Chiu et al. disclose that “[i]n some embodiments described herein, the bispecific EGFR/c-Met antibody of the invention has a biantennary glycan structure with fucose content of about between 1% to about 15%...”
With respect to claim 8-10, at column 58, Chiu et al. disclose that the bispecific EGFR/c-Met antibody of the invention may be administered intravenously at a dosage of 500 mg or 1000 mg.
With respect to claims 13 and 14, at column 58, Chiu et al. disclose that “[t]he bispecific EGFR/c-Met antibodies of the invention may be administered to a patient by any suitable route, for example parentally by intravenous (IV) infusion or bolus injection, intramuscularly or subcutaneously or intraperitoneally. IV infusion can be given over as little as 15 minutes, but more often for 30 minutes, 60 minutes, 90 minutes or even 2 or 3 hours. The bispecific EGFR/c-Met antibodies of the invention may also be injected directly into the site of disease (e.g., the tumor itself). The dose given to a patient having a cancer is sufficient to alleviate or at least partially arrest the disease being treated (“therapeutically effective amount”)…”
With respect to claims 15 and 16, at column 59, Chiu et al. disclose that “[a]dministration of the bispecific EGFR/c-Met antibody of the invention may be repeated after one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, one month, five weeks, six weeks, seven weeks, two months, three months, four months, five months, six months or longer.”
With respect to claim 18, at column 54, Chiu et al. disclose that “[i]n some methods described herein, the antibodies of the invention may be used to treat a subject having cancer that is resistant or has acquired resistance to treatment with one or more EGFR inhibitors.”
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 19 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11 and 16 of copending Application No. 17/398,294 (reference application), in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017), as applied to claims 1, 2, 5, 7-18 and 26, and further in view of Wang et al. (Exp Hematol Oncol, 10(45): 1-5, 2021).
The teachings of Wang et al. are detailed above.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of the conflicting claims and Chiu et al. with those of Wang et al. to arrive at a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, wherein said subject has received a prior treatment of anti-VEGF/VEGFR therapy (bevacizumab). One of ordinary skill in the art would have been motivated to do so, because the conflicting claims and Chiu et al. teach a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, wherein the subject has received a prior treatment. Further based upon the teachings of Wang et al., one of ordinary skill in the art would appreciate that some HCC patients who are treated with atezolizumab/bevacizumab therapy will progress following treatment, and these patients will be in need of other treatments to address said cancer progression. One of ordinary skill in the art would have had ample motivation to administer the treatment method of the conflicting claims and Chiu et al. to HCC patients who have progressed following atezolizumab/bevacizumab therapy, because there would have been a reasonable expectation that the treatment method of the conflicting claims and Chiu et al. would provide a therapeutic benefit to HCC patients who have progressed following atezolizumab/bevacizumab therapy.
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al. and Wang et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-4 and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 15, and 17 of copending Application No. 18/222,093 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other, because both sets of claims encompass a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody comprising: SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 20, and SEQ ID NO: 21.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 5, 7-18, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 15, and 17 of copending Application No. 18/222,093 (reference application), as applied to claims 1-4 and 6, and further in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017).
The teachings of Chiu et al. are disclosed above. It would have been prima facie obvious to modify the conflicting claims to include the bispecific EGFR/c-Met antibody characteristics recited in the following claims, because the resultant invention would be expected to provide a therapeutic benefit to HCC patients.
With respect to claim 5, at column 42, Chiu et al. disclose that bispecific antibodies of the invention may comprise heavy chains of the IgG1 isotype.
With respect to claim 7, at column 49, Chiu et al. disclose that “[i]n some embodiments described herein, the bispecific EGFR/c-Met antibody of the invention has a biantennary glycan structure with fucose content of about between 1% to about 15%...”
With respect to claim 8-10, at column 58, Chiu et al. disclose that the bispecific EGFR/c-Met antibody of the invention may be administered intravenously at a dosage of 500 mg or 1000 mg.
With respect to claims 13 and 14, at column 58, Chiu et al. disclose that “[t]he bispecific EGFR/c-Met antibodies of the invention may be administered to a patient by any suitable route, for example parentally by intravenous (IV) infusion or bolus injection, intramuscularly or subcutaneously or intraperitoneally. IV infusion can be given over as little as 15 minutes, but more often for 30 minutes, 60 minutes, 90 minutes or even 2 or 3 hours. The bispecific EGFR/c-Met antibodies of the invention may also be injected directly into the site of disease (e.g., the tumor itself). The dose given to a patient having a cancer is sufficient to alleviate or at least partially arrest the disease being treated (“therapeutically effective amount”)…”
With respect to claims 15 and 16, at column 59, Chiu et al. disclose that “[a]dministration of the bispecific EGFR/c-Met antibody of the invention may be repeated after one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, one month, five weeks, six weeks, seven weeks, two months, three months, four months, five months, six months or longer.”
With respect to claim 18, at column 54, Chiu et al. disclose that “[i]n some methods described herein, the antibodies of the invention may be used to treat a subject having cancer that is resistant or has acquired resistance to treatment with one or more EGFR inhibitors.”
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 19 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 15, and 17 of copending Application No. 18/222,093 (reference application), in view of Chiu et al. (US PAT 9,593,164, issue date: 03/14/2017), as applied to claims 1-18 and 26, and further in view of Wang et al. (Exp Hematol Oncol, 10(45): 1-5, 2021).
The teachings of Wang et al. are detailed above.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of the conflicting claims and Chiu et al. with those of Wang et al. to arrive at a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, comprising: SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 20, and SEQ ID NO: 21, wherein said subject has received a prior treatment of anti-VEGF/VEGFR therapy (bevacizumab). One of ordinary skill in the art would have been motivated to do so, because the conflicting claims and Chiu et al. teach a method of treating liver cancer, specifically, hepatocellular carcinoma, comprising administering to a subject in need thereof a bispecific EGFR/c-Met antibody, wherein the subject has received a prior treatment. Further based upon the teachings of Wang et al., one of ordinary skill in the art would appreciate that some HCC patients who are treated with atezolizumab/bevacizumab therapy will progress following treatment, and these patients will be in need of other treatments to address said cancer progression. One of ordinary skill in the art would have had ample motivation to administer the treatment method of the conflicting claims and Chiu et al. to HCC patients who have progressed following atezolizumab/bevacizumab therapy, because there would have been a reasonable expectation that the treatment method of the conflicting claims and Chiu et al. would provide a therapeutic benefit to HCC patients who have progressed following atezolizumab/bevacizumab therapy.
Therefore the instant claims are prima facie obvious over the conflicting claims in view of Chiu et al. and Wang et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-19, 25, and 26 are rejected under non-statutory double patenting over the reference patents listed in the following table:
Patent Number
Brief Description of the Invention
Pertinent Claims
12,448,455
Combination Therapies with Bispecific Anti-EGFR/c-met Antibodies and Third Generation EGFR Tyrosine Kinase Inhibitors
1, 6, and 7
The patent specified above comprises/recites the same/similar active steps for treating a subject with a bispecific EGFR/c-Met antibody. Even if the method of treating with a bispecific EGFR/c-Met antibody is not identical to the instant application, the inventions are analogous to Chiu et al., who teaches the instant method of treating a subject with a bispecific EGFR/c-Met antibody. Thus, the above-mentioned reference patent, in view of Chiu et al. and Wang et al. would render any method of treating HCC with a bispecific EGFR/c-Met antibody obvious. The additional limitations of the instant claims would further be rendered obvious under the same art references utilized above.
In the interest of compact prosecution, Applicant is invited to indicate whether or not the differences between the instant claims and the patented claims are obvious in view of the cited references as they read on treating subjects with a bispecific EGFR/c-Met antibody.
Similarly, claims 1-19, 25, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the copending applications listed in the following table:
Application Number
Brief Description of the Invention
Pertinent Claims
18/990,769
Combination Therapies and Patient Stratification with Bispecific Anti-EGFR/c-Met Antibodies
1-3, 5, and 15
19/338,193
Combination Therapies with Bispecific Anti-EGFR/c-Met Antibodies and 3rd Generation Tyrosine Kinase Inhibitors4
1, 2, 8, and 9
19/338,613
Bispecific EGFR/c-MET Antibodies
1, 11, and 16
The applications specified above comprises/recites the same/similar active steps for treating a subject with a bispecific EGFR/c-Met antibody. Even if the method of treating with a bispecific EGFR/c-Met antibody is not identical to the instant application, the inventions are analogous to Chiu et al., who teaches the instant method of treating a subject with a bispecific EGFR/c-Met antibody. Thus, the above-mentioned reference applications, in view of Chiu et al. and Wang et al. would render any method of treating HCC with a bispecific EGFR/c-Met antibody obvious. The additional limitations of the instant claims would further be rendered obvious under the same art references utilized above.
In the interest of compact prosecution, Applicant is invited to indicate whether or not the differences between the instant claims and each of the copending sets of claims are obvious in view of the cited references as they read on treating subjects with a bispecific EGFR/c-Met antibody.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642