DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/17/25 has been entered.
3. Claims 1, 7-10, 12-37, 43, 44 and 52-58 are pending upon entry of amendment filed on 9/17/25.
Claims 14-37 stand withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to nonelected invention.
Claim 1, 7-10, 12, 13, 43-44 and 52-58 readable upon SEQ ID NO:1-2 are under consideration in the instant application.
4. The following rejections remain.
5. 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 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.
6. 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 of this title, 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.
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.
7. Claim 1, 7-10, 12, 13, 43-44 and 52-58 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pub. 2015/0352224 (IDS reference, of record) in view of U.S. Pub.2007/0031402 (of record) for the reasons set forth in the office action mailed on 3/17/25.
The ‘224 publication teaches antibody drug conjugates set forth in claimed formula I (p. 79-129) with various antibody of interests (claims 1-52) and pharmaceutical compositions thereof. The ‘224 publication further teaches exatecan conjugates (e.g. a part of conjugate of the claimed formula I) acts as topoisomerase I inhibitor exhibiting antitumor effect ([0002]).
The disclosure of the ‘224 publication differs from the instant claimed invention in that it does not teach the use of histidine buffer, sucrose, and or surfactant as in claim 1 and use of SEQ ID NO:1-2 as in claims 7-9 of the instant application, respectively.
The ‘402 publication teaches immunoconjugate compositions comprising trastuzumab, 5-20 mM of histidine buffer at pH 5-6 in the presence of 5-10% sucrose and 0.005-0.2 % polysorbate (claims 1-21). The concentration of conjugate ranges from 0.01-25mg ([126]). Given that the trastuzumab (note p. 46-47 of the instant application) comprises claimed SEQ ID NO:1-2, it meets the limitations of claims 7-9 of the instant application.
Further, the ‘402 publication teaches cytotoxic effect of immunoconjugates (p. 9-10) and the formulation improves stability by reducing particles and aggregates (examples). IN example 1, black background container is used and claim 43 reciting brown vial is included in this rejection.
In addition, the ‘402 publication teaches that the composition may be frozen, lyophilized (p. 11) and the administration routes include injections ([0117-119]) as well as the aqueous injection (e.g. intravenous) as in claim 39 of the instant application.
Claims 12-13 reciting specific excipient concentrations are included in this rejection as optimization within prior art condition or through routine experimentation is not inventive. See MPEP 2144.05.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, sucrose, polysorbate and trastuzumab as in the ‘402 publication into the immunoconjugate taught by the ‘224 publication.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the excipients are known to improve stability by reducing aggregates and utilization of trastuzumab extends therapeutic applicability.
From the teachings of references, it would have been obvious to one of ordinary skill in art to combine the teachings of the references and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of the ordinary in the art at the time of invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that the combination of the references fails to teach all the limitations of claimed invention. Applicant has further asserted that the prior art formulation cannot be relied on the lyophilized form while the claimed formulation is lyophilized and the claimed pH is not taught.
Applicant has asserted that the ADC of the claimed invention requires GGFG while the ‘224 publication includes hydrophilic amino acid other than glycine at N terminus and does not disclose GGFG (p. 10 of the response filed on 6/11/24). The combination of the references does not provide no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
In addition, the exhibits provided discuss unique challenges and the linker in antibody drug conjugate (ADC) dictates stability and one of the ordinary skill would not select the formulations that is suitable for one linker to another. The linkers induce aggregations in ADC and the linkers of the ‘402 publication and the ‘224 publication are different.
Unlike Applicant’s assertion, the lyophilized form of ADC is widely known as evidenced by the ‘224 publication as well as the ‘402 publication.
The exatecan derivatives of drugs may be lyophilized [1584-1585] and the ‘402 publication teaches lyophilization is available (p.11-12). Regardless, the actual injection is deemed in reconstituted form and the lyophilized form of ADC is supported by the cited prior art.
Further, the ‘224 publication teaches addition of buffering agent corresponding to administration ([1581-1582]) and physiological pH encompassed by the claimed pH is suggested. Indeed, pH 6 in PBS is used throughout the examples and pH 5-6 is supported by the ‘402 publication (claims). Applicant is reminded that the structure and characteristics are inseparable and the combination of the prior art is expected to show the properties. Although the drug conjugate is dissolved in water and exhibits pH of 5-6, the claimed composition is in lyophilized form. If the criticality relies on the pH of intermediate form of the ADC, the unexpected property should be recited.
In addition, Applicant’s assertion that the ‘224 publication does not teach or suggest GGFG, [400-423] of the ‘224 publication suggests GGFG motives the additional amino acid such as D or K on the N terminus is where the linker is conjugated and the GGFG motives is suggested. As such, the GGFG motif required by the claimed invention it taught by the ‘224 publication and the combination of the references remains obvious.
However, the exhibits are silent about specific linker. The linker is defined to include SPDB, SMCC by the ‘402 publication ([109-111]) share the same structures or inclusive of the derivatives (p.9-11, 32). The ‘224 publication discusses formulation of ADC in any buffer solution or bolus for administration (p. 68). As such, one of the ordinary skill in the art would have expected reasonable success in combining the references. The linker reads on moiety linking a drug and antibody.
Unlike Applicant’s assertion, the ‘402 publication teaches the addition of polysorbate and excipients reduce aggregates in immunoconjugate formulations (p. 1-2) and specific concentrations of polysorbate 20 or polysorbate 80 upto 1% (Examples, claims 1-21) in the presence of 0.5-10mg of immunoconjugate. As studied in the ‘402 publication, the nature of antibody is also critical in maintaining the stability. The antibodies with different binding activity and different conjugate are stable in buffer comprising histidine, sucrose and polysorbate. If Applicant attempts to argue each specific composition is required for each drug conjugate, specific concentrations of excipients is required to be recited (note p. 14 of the ‘402 publication or claims).
Unless specific concentrations of histidine buffer at specific pH and sucrose in immunoconjugate formulations of target antibody, there is reasonable expectation of success in producing the claimed antibody by adding histidine, sucrose as stabilizing excipients in light of the ‘402 publication.
Further, the ‘224 publication discloses that the composition may be lyophilized ([1583], p.68). As such, the limitations of the currently amended claims are met.
The asserted unexpected properties of showing reduction of particles deemed an expected property of the immunoconjugate with histidine, sucrose and polysorbate as the formulations of the ‘402 publication shows “substantially free of particles”. The rejection is maintained.
8. Claim 1, 7-10, 12, 13, 43-44 and 52-58 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pub.2007/0031402 (of record) in view of U.S. Pub. 2015/0352224 (IDS reference, of record) for the reasons set forth in the office action mailed on 3/17/25.
The teachings of the ‘402 and 224 publications have been discussed, supra.
The disclosure of the ‘402 publication differs from the claimed invention in that it does not use the claimed Formula I as in claim 1 of the instant application.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize the different immunoconjugate as taught by the ‘224 publication into the immunoconjugate composition taught by the ‘402 publication.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the immunoconjugate taught by the ‘224 publication is known to acts as topoisomerase I inhibitor exhibiting antitumor effect ([0002]) with different mechanism of antitumor effect.
From the teachings of references, it would have been obvious to one of ordinary skill in art to combine the teachings of the references and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of the ordinary in the art at the time of invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that there is no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
IN light of the discussion above in section 7 of this office action, the rejection is maintained.
9. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
10. Claims 1, 7-10, 12, 13, 43-44 and 52-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. 9,872,924 in view of U.S. Pub.2007/0031402.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘924 patent recite an antibody conjugate set forth in the claimed formula I and the pharmaceutical compositions thereof.
The claims of the ‘924 patent differ from the claimed invention in that it does not teach the use of histidine, sucrose and surfactant as in claim 1 of the instant application.
The ‘402 publication teaches use of histidine, sucrose and polysorbate in the immunoconjugate formulation and the excipients stabilize immunoconjugate by reducing aggregates and improve stability.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, sucrose, polysorbate and trastuzumab as in the ‘402 publication into the immunoconjugate taught by the ‘924 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the excipients are known to improve stability by reducing aggregates and utilization of trastuzumab extends therapeutic applicability.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that there is no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
IN light of the discussion above in section 7 of this office action, the rejection is maintained.
11. Claims 1, 7-10, 12, 13, 43-44 and 52-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-14 of U.S. 9,850,312 in view of U.S. Pub.2007/0031402.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘312 patent recite an antibody conjugate set forth in the claimed formula I and the pharmaceutical compositions thereof.
The claims of the ‘312 patent differ from the claimed invention in that it does not teach the use of histidine, sucrose and surfactant as in claim 1 of the instant application.
The ‘402 publication teaches use of histidine, sucrose and polysorbate in the immunoconjugate formulation and the excipients stabilize immunoconjugate by reducing aggregates and improve stability.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, sucrose, polysorbate and trastuzumab as in the ‘402 publication into the immunoconjugate taught by the ‘312 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the excipients are known to improve stability by reducing aggregates and utilization of trastuzumab extends therapeutic applicability.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that there is no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
IN light of the discussion above in section 7 of this office action, the rejection is maintained.
12. Claims 1, 7-10, 12, 13, 43-44 and 52-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 18 of U.S. 9,808,537 in view of U.S. Pub.2007/0031402.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘537 patent recite an antibody conjugate set forth in the claimed formula I and the pharmaceutical compositions thereof.
The claims of the ‘537 patent differs from the claimed invention in that it does not teach the use of histidine, sucrose and surfactant as in claim 1 of the instant application.
The ‘402 publication teaches use of histidine, sucrose and polysorbate in the immunoconjugate formulation and the excipients stabilize immunoconjugate by reducing aggregates and improve stability.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, sucrose, polysorbate and trastuzumab as in the ‘402 publication into the immunoconjugate taught by the ‘537 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the excipients are known to improve stability by reducing aggregates and utilization of trastuzumab extends therapeutic applicability.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that there is no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
IN light of the discussion above in section 7 of this office action, the rejection is maintained.
13. Claims 1, 7-10, 12, 13, 43-44 and 52-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-14 of U.S. 10,227,417 in view of U.S. Pub.2007/0031402.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘417 patent recite an antibody conjugate set forth in the claimed formula I and the pharmaceutical compositions thereof.
The claims of the ‘417 patent differs from the claimed invention in that it does not teach the use of histidine, sucrose and surfactant as in claim 1 of the instant application.
The ‘402 publication teaches use of histidine, sucrose and polysorbate in the immunoconjugate formulation and the excipients stabilize immunoconjugate by reducing aggregates and improve stability.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, sucrose, polysorbate and trastuzumab as in the ‘402 publication into the immunoconjugate taught by the ‘417 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the excipients are known to improve stability by reducing aggregates and utilization of trastuzumab extends therapeutic applicability.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that there is no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
IN light of the discussion above in section 7 of this office action, the rejection is maintained.
14. Claims 1, 7-10, 12, 13, 43-44 and 52-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 18 of U.S. 10,195,288 in view of U.S. Pub.2007/0031402.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘288 patent recites an antibody conjugate set forth in the claimed formula I and the pharmaceutical compositions thereof.
The claims of the ‘288 patent differ from the claimed invention in that it does not teach the use of histidine, sucrose and surfactant as in claim 1 of the instant application.
The ‘402 publication teaches use of histidine, sucrose and polysorbate in the immunoconjugate formulation and the excipients stabilize immunoconjugate by reducing aggregates and improve stability.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize histidine, sucrose, polysorbate and trastuzumab as in the ‘402 publication into the immunoconjugate taught by the ‘288 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the excipients are known to improve stability by reducing aggregates and utilization of trastuzumab extends therapeutic applicability.
Applicant’s response filed on 9/17/25 has been fully considered but they were not persuasive.
Applicant has asserted that there is no motivation to combine the references and lack reasonable expectation of success. Applicant has further asserted that the claimed formulations possess unexpected advantages in reducing fine particles disclosed in Table 8 and Fig 7.
IN light of the discussion above in section 7 of this office action, the rejection is maintained.
15. No claims are allowable.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached on Mon-Fri 8:30-5. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Yunsoo Kim
Patent Examiner
Technology Center 1600
December 4, 2025
/YUNSOO KIM/Primary Examiner, Art Unit 1641