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 11/20/2025, are acknowledged.
Claims 1-120 are canceled.
Claim 130 is new.
Claims 121-130 are pending.
As such, claims 121-130 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/20/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
The objections to the drawings are withdrawn in part. Issues regarding minor informalities have been sufficiently addressed through amendments to the drawings and specification on 11/20/2025. Specifically, the following objections are withdrawn:
Fig. 9A recites “CTG-0707” but the specification recites “CTG-0353” (see [00105]);
Fig. 9B recites “CTF-0353” but the specification recites “CTG-0707” (see [00105]);
Fig. 10A recites “HN2564” but the specification recites “HN2574” (see [00106]);
Fig. 11B recites “ES0214” but the specification recites “ES0147” (see [00107]); and,
Fig. 11C recites “ES0147” but the specification recites “ES0214” (see [00107]).
The specification objections are withdrawn in part. Issues regarding minor informalities and trademarks/names have been sufficiently addressed through amendments to the specification on 11/20/2025.
Withdrawn Rejections
Applicant’s remarks, see pages 52 and 53, filed on 11/20/2025, with respect to claims 121-129 provisionally rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over claims 72-74, 77, 92, 114, 115, 117, 118, 120-123, 125, 141, 163, 164, 166, 167, 226, 287, 288, 358-360, 363, 378, 400, 401, 403, 404, and 461-503 of co-pending US Application No. 19/000,442 in view of Winters et al have been fully considered and are persuasive. Examiner acknowledges that the ‘442 application claims were amended to no longer recite the sequences recited in the present invention. As such, the provisional rejection of claims 121-129 on the ground of nonstatutory double patenting is withdrawn.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.
Claim 130 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 130 recites the limitation “wherein the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 are determined according to the Kabat numbering system, Chothia numbering system, AbM numbering system, Contact numbering system, IMGT numbering system, or a combination thereof”. This limitation incorporates a reference in the claim (e.g., Kabat and Chothia numbering systems are based on specific papers). MPEP2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Further, claim 130 contains the trademark/trade name IMGT. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an amino acid numbering system and, accordingly, the identification/description is indefinite.
As such, claim 130 is rejected. Examiner suggests amending the claim to recite the EU numbering system.
Maintained Objections and Rejections
Drawings
The drawings are objected to because:
Fig. 9C recites “CTG-1076 Bladder” but the specification recites “CTG-0786… head & neck cancer” (see [00105]); and
Fig. 9D recites “CTG-0786 Head and Neck” but the specification recites “CTG-1076… bladder” (see [00105]
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Applicant’s Arguments
Applicants respectfully submit that the specification is amended to correct the inadvertent obvious errors in the specification in “Brief Description of Drawings” section for Figs. 9A, 9B, 9C, 9D, 11B and 11C. See page 41 of the Remarks filed 11/20/2025.
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive. Examiner acknowledges the amendments made to the specification; however, a discrepancy remains with the descriptions of Fig. 9C and Fig. 9D. Specifically, the description of Fig. 9C recites “head & neck cancer” while the drawing says “bladder”, and the description of Fig. 9D recites “bladder” while the drawing says “head and neck”. As such, the objections of Fig. 9C and Fig. 9D is maintained.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 41, 114, 115, and 116). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Applicant’s Arguments
Applicant requests reconsideration and withdrawal of the hyperlink objection (see pages 41 and 42 of the Remarks filed 11/20/2025). Applicant asserts that pages 114-115, paragraph [00401] and page 116, paragraph [00410] to remove the prefix “http://”. With respect to the objection to page 41 of the specification, Applicants respectfully submit that there are no embedded hyperlinks and/or other form of browser-executable codes on this page. Paragraph [00158] on page 41 refers to an online book by listing the top-level domain name without any prefix such as http:// or other browser-executable code as: www.ncbi.nlm.nih.gov/books/NBK92434/.
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive. Examiner acknowledges the amendments to the specification. However, the amendments do not overcome the rejection because even without the http:// prefix, the hyperlinks remain browser-executable by listing the “.html” at the end of the link. As stated in MPEP 608.01(VII): When a patent application with embedded hyperlinks and/or other forms of browser-executable code issues as a patent (or is published as a patent application publication) and the patent document is placed on the USPTO webpage, when the patent document is retrieved and viewed via a web browser, the URL is interpreted as a valid HTML code and it becomes a live web link. When a user clicks on the link with a mouse, the user will be transferred to another webpage identified by the URL, if it exists, which could be a commercial website. USPTO policy does not permit the USPTO to link to any commercial sites since the USPTO exercises no control over the organization, views or accuracy of the information contained on these outside sites.
As such, the specification objection is maintained.
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 121-122, 124-125, and 128-130 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 121 and 125 require complementarity determining regions (CDRs) from heavy and light chain sequences without actually setting forth the CDR sequences. There are several well-established methods to determine CDRs. Using common methods to identify the CDRs produces variable CDR sequences. For example, numbering by the Chothia method produces CDRs that differ in residues than numbering by the Kabat method. Therefore, the methods do not name the same CDRs, and one of skill in the art would not know which of these embodiments would meet the requirements of the claims. The differences in CDRs may have different affinities that would not be capable of the required functions. While the specification discloses the CDR sequences for different numbering methods (e.g., see Table 8), Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant’s Arguments
Applicant respectfully traverses the 112(b) rejection (see pages 46 and 47 of the Remarks filed on 11/20/2025).
Applicants respectfully submit that the instant claims set out and circumscribe the features of the claimed antibody-drug conjugate, with a reasonable degree of clarity. The claims clearly recite that the antigen binding protein (Ab) has the features of a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH-CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 151, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 152. As described in the specification, CDRs are well recognized in the art and have been defined by the Kabat, Chothia, AbM, Contact, IMGT and Exemplary numbering methods… Accordingly, a person skilled in the art could readily understand the metes and bounds of the CDR sequences in the claimed antibody-drug conjugate.
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive.
Examiner acknowledges new claim 130 which recites several numbering systems. However, the content of the claims and Applicant’s remarks provide evidence that the antigen binding protein could create CDRs in multiple ways making the exact CDRs unclear. As stated above, the methods [of numbering] do not name the same CDRs, and one of skill in the art would not know which of these embodiments would meet the requirements of the claims. The differences in CDRs may have different affinities that would not be capable of the required functions. As such, the 112(b) rejection is maintained. Examiner suggests amending the claims to recite the EU numbering system.
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.
12,215,167
Claims 121-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,215,167 B2 in view of Winters et al (WO 2015/095953 A1, publication date: 07/02/2015; provided in the IDS filed 08/11/2025).
The ‘167 patent is drawn to an antibody which binds to the extracellular domain of human Tissue Factor (TF), wherein the antibody comprises a VH-CDR1, a VH-CDR2, and a VH-CDR3 comprising the amino acid sequences of the VH- CDR1, the VH-CDR2, and the VH-CDR3, respectively, as set forth in a VH comprising the amino acid sequence of SEQ ID NO: 151, and a VL-CDR1, a VL-CDR2, and a VL-CDR3 comprising the amino acid sequences of the VL-CDR1, the VL-CDR2, and the VL-CDR3, respectively, as set forth in a VL comprising the amino acid sequence of SEQ ID NO: 152 (see claims 1-11). SEQ ID Nos: 151 and 152 shares 100% identity to instant SEQ ID Nos: 151 and 152, respectively. Consequently, the CDR sequences in the ‘167 patent share 100% identity with the instant CDR sequences comprising the same SEQ ID NO. identifier (i.e., the ‘167 patent SEQ ID NO: 115 shares 100% identity with instant SEQ ID NO: 115, etc.). Additionally, the ‘167 patent is drawn to a pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable excipient (see claim 4).
The difference between the instant claims and the ‘167 patent is that the instant claims are drawn to an antibody-drug conjugate comprising an antigen binding protein and one or more linker-toxin moieties. However, as stated above, the ‘167 patent is drawn to an antibody that shares the same sequence identity as the instant application. Further, with respect to the linker-toxin moiety, Winters et al disclose of sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates (see Abstract). Specifically, Winters et al disclose of antibodies conjugated to Compound O which shares the same structure as the linker-toxin moiety as the instant application (see Example 16 and pg. 195). Furthermore, Winters et al disclose that an antibody conjugated to Compound O had a relatively low EC50 against killing human gastric carcinoma cell line NCI-N87 (see Biological Example 1 and Table 1). Additionally, Winters et al disclose that conjugates comprising Compound O released by cathepsin B in vitro (see pg. 194 and 195).
As such, it would have been obvious to modify the antibody of the ‘167 patent with the linker-toxin described by Compound O to develop the present invention because the art has demonstrated that this particular linker-toxin enhanced the potency of the antibody to which it is conjugated. Lastly, 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, antibody-drug conjugates, 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-drug conjugates are akin to the variables discussed in the cited MPEP passage, because said antibody-drug conjugates 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 antibody-drug conjugates which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited antibody-drug conjugates 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 antibody-drug conjugates recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
18/015,532
Claims 121-130 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 12, 13, 23, 50, 51, 63, 102, 103, 110, 112, 114, 140, and 143 of copending Application No. 18/015,532 in view of Winters et al (WO 2015/095953 A1, publication date: 07/02/2015; provided in the IDS filed 08/11/2025).
The ‘532 application is drawn to a method of treating an inflammatory disease in a subject in need thereof comprising administering to the subject an isolated antibody wherein the antibody binds to Tissue Factor (TF), wherein the antibody binds human TF at a human TF binding site that is distinct from a human TF binding site bound by human FVIIa (see claim 1). The ‘532 application is drawn to the method of claim 1, wherein: (a) the antibody does not inhibit human thrombin generation as determined by thrombin generation assay (TGA); and/or (b) the isolated human antibody does not inhibit or inhibits human thrombin generation to a lesser extent, as determined by thrombin generation assay (TGA), compared to a reference antibody comprising a heavy chain variable domain (VH) sequence of SEQ ID NO:821 and a light chain variable domain (VL) sequence of SEQ ID NO:822, optionally wherein binding between the isolated antibody and a variant TF extracellular domain comprising a mutation at amino acid residue 149 of the sequence shown in SEQ ID NO:810 is less than 50% of the binding between the isolated antibody and the extracellular domain of TF of the sequence shown in SEQ ID NO:810, as determined by the median fluorescence intensity value of the isolated antibody relative to an isotype control in a live cell staining assay; and/or (c) the antibody comprises:(i) all three heavy chain Complementary Determining Regions (CDRs) and all three light chain CDRs from an antibody group in Table 35 wherein the all three heavy chain CDRs and the all three light chain CDRs are from the same antibody group, or (ii) all three heavy chain CDRs and all three light chain CDRs from an antibody in any one of Tables 15-34, wherein the all three heavy chain CDRs and the all three light chain CDRs are from the same antibody, optionally comprising all three heavy chain CDRs and all three light chain CDRs from: the antibody designated 25A, the antibody designated 25A5, the antibody designated 25A5-T, the antibody designated 25G. the antibody designated 25G1, the antibody designated 25G9, the antibody designated43B, the antibody designated 43B1, the antibody designated 43B7, the antibody designated 43D,the antibody designated 43D7, the antibody designated 43D8, the antibody designated 43E, or the antibody designated 43Ea; or(iii) a VH sequence and VL sequence from Table 14, wherein the VH and VL sequences are from the same group in Table 14; or (iv) a VH sequence and VL sequence from Table 13, wherein the VH and VL sequences are from the same clone in Table 13 (see claim 13). Table 13 discloses of clone 25A3 which comprises SEQ ID Nos: 151 and 152. SEQ ID Nos: 151 and 152 share 100% identity with instant SEQ ID Nos: 151 and 152, respectively. The ‘532 application is drawn to the antibody comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID Nos: 926 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 927 (see claim 23). SEQ ID Nos: 926 and 927 share 100% identity with instant SEQ ID Nos: 926 and 927, respectively.
The difference between the instant claims and the ‘532 application is that the instant claims are drawn to an antibody-drug conjugate whereas the ‘532 application is drawn to a method of using a claimed antibody. 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.
Additionally, with respect to the antibody-drug conjugate, Winters et al disclose of sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates (see Abstract). Specifically, Winters et al disclose of antibodies conjugated to Compound O which shares the same structure as the linker-toxin moiety as the instant application (see Example 16 and pg. 195). Furthermore, Winters et al disclose that an antibody conjugated to Compound O had a relatively low EC50 against killing human gastric carcinoma cell line NCI-N87 (see Biological Example 1 and Table 1). Additionally, Winters et al disclose that conjugates comprising Compound O released by cathepsin B in vitro (see pg. 194 and 195).
As such, it would have been obvious to modify the antibody of the ‘532 antibody with the linker-toxin described by Compound O to develop the present invention because the art has demonstrated that this particular linker-toxin enhanced the potency of the antibody to which it is conjugated. Lastly, 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, antibody-drug conjugates, 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-drug conjugates are akin to the variables discussed in the cited MPEP passage, because said antibody-drug conjugates 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 antibody-drug conjugates which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited antibody-drug conjugates 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 antibody-drug conjugates 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 respectfully disagrees with the rejections (see pages 47-52 of the Remarks filed 11/20/2025).
With respect to the ‘167 patent, Applicant argues that the claims of the ‘167 patent do not recite anti-TF ADCs comprising one or more linker-toxin moieties represented by Formula VIII, as recited in independent claim 121 or an antibody-drug conjugate of Formula IX as recited in independent claims 126 and 127… Applicant argues that Winters et al do not teach or suggest conjugates comprising the antibodies of the antibody drug conjugates of the amended claims of the instant application. Winters et al purportedly describe the claimed linker-toxin moiety in Example 16, page 195, however the Office Action fails to recognize or acknowledge that a total of about 30 linker-toxins are described in Winters et al. With respect to the low EC50 of Compound O against killing human gastric carcinoma cell line NCI-N87, the Office Action fails to recognize or acknowledge the fact that there are at least three other linker toxins in Winters et al., i.e., Compound P, Q and that have equal or lower EC50 as that of Compound O, against killing human gastric carcinoma cell line NCI-N87… With respect to release of antibody-drug conjugates by cathepsin B in vitro, the Office Action fails to recognize or acknowledge that Winters et al describe at least 15 other antibody drug-conjugates … As such, Applicants respectfully submit that the Office is only able to select and combine the particular antibody of the claims of the instant application with the specific linker-payload of Example 16 based on impermissible hindsight of the claims of the instant application, and the double patenting rejection should be withdrawn for this reason alone… The instant application provides significant amount of experimental data that would rebut a presumption that the conjugates of the amended claims are obvious variants of the antibodies of the claims of the ‘167 patent. In this regard, the Federal Circuit has made clear that in analyzing a nonstatutory double patenting rejection, just like obviousness under § 103, a court must consider objective indicia evidence.
With respect to the ‘532 application, Applicant argues that the ‘532 application is not a proper non-statutory double patenting reference. A later-filed, later expiring unrelated patent is not a proper non-statutory double patenting reference… In addition, MPEP Section 804 (1)(b)(i) (Ninth Edition, Revision 11.2024) states: If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent… Relying on the Federal Circuit's recent decision in Allergan, the Patent Trial and Appeal Board recently decided in Exparte Baurin that a later- filed, but earlier-issued patent was not a proper reference patent for a non-statutory double patenting rejection of an application in a different patent family. Ex Parte Baurin, Appeal 2024- 002920, Appl. No. 17/135,529 (PTAB Nov. 6, 2024). The '532 Application was filed on January 10, 2023, which is a national stage of International Patent Application No. PCT/US2021/041192, filed July 10, 2021, which claims priority to a US Provisional Application filed on July 10, 2020. The patent issuing from the '532 Application expires no earlier than July 10, 2041. In contrast, the subject application was filed on January 3, 2022, and is a national stage of International Patent Application No. PCT/US2020/040711, filed on July 2, 2020, which claims priority to a US Provisional Application filed on July 3, 2019. The subject application if issued would have an expiration date July 2, 2040 without PTA or PTE, i.e., before the expiration date (July 10, 2041) of the '532 Application without PTA or PTE.
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, 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). As stated in the rejection, the ‘167 patent recite the anti-TF antibody of the present application and Winters et al disclose of the structure of the instant linker-toxin moieties. As such, it would have been obvious to modify the antibody of the ‘167 patent with the linker-toxin described by Winters et al to develop the present invention because the art has demonstrated that this particular linker-toxin enhanced the potency of the antibody to which it is conjugated.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). While Winters et al recites several species of linker toxins, only four linker toxins had equal to low EC50 values and released to cathepsin B in vitro: Compounds O, P, Q, and Z; see Table 1 and page 195, lines 7-11). Further, it is noted that these four compounds are structurally similar (i.e., each comprise (S)-1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,6,9-trioxa-13-azadecanamido)), thus it would have been obvious to try any of the four compounds, including Compound O, to conjugate to the claimed antibody because one of skill in the art would have a reasonable expectation that any of these species would function similarly (see MPEP 2143(I)(E) and 2144.08).
Applicant is reminded that a rejection under double patenting precludes the identification of allowable subject matter. Applicant has not filed a terminal disclaimer, and the claims remain rejected for reasons set forth above.
The Examiner acknowledges that MPEP 1490 states that if the provisional ODP rejections in both applications are the only rejections remaining in those applications, the examiner should then withdraw the provisional ODP rejection in the earlier-filed application thereby permitting that application to issue without need of a terminal disclaimer. The instant application has an effective filing date of July 3, 2019, while the copending application has an effective filing date of July 10, 2020. The instant application is therefore the earlier filed application. Further, with respect to Applicant’s arguments regarding Ex Parte Baurin, Appeal 2024- 002920, Appl. No. 17/135,529 (PTAB Nov. 6, 2024), the present application does not reflect the facts of the ‘529 case because the ‘529 ODP rejections in question were the only rejections remaining whereas this provisional double patenting rejection is not the only rejection remaining, and therefore the rejection is maintained.
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As such, the double patenting rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANAYA L MIDDLETON whose telephone number is (571)270-5479. The examiner can normally be reached M-F 9:30AM - 6PM with flex.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674