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
The amendment filed January 27, 2026, is acknowledged and has been entered. Claims 1 and 9 have been amended. Claims 4, 6, 10, 13 and 23 have been canceled.
Claims 1, 9, 16, 19-20, 22, 24, 26, 29, 31, 34, 38, 41, 43 and 46 are pending. Claims 26, 29, 31, 34, 38, 41, 43 and 46 are withdrawn from further consideration by the examiner, under 37 CFR 1.142(b), as being drawn to a non-elected invention or species of election.
Claims 1, 9, 16, 19-20, 22 and 24 are under examination.
Grounds of Rejection Withdrawn
Unless specifically reiterated below, Applicant’s amendments have obviated or rendered moot the grounds of objection and rejection set forth in the previous Office action mailed.
Grounds of Rejection Maintained
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 9, 16, 19-20, 22 and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a HER2 positive tumor by a method comprising the steps of claim 1, does not reasonably provide enablement for the full scope of the claimed methods such as preventing or alleviating a HER2 positive tumor by a method comprising the steps of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The amount of guidance, direction, and exemplification disclosed in the specification, as filed, would not be sufficient to enable the skilled artisan to use the claimed invention at the time the application was filed without undue experimentation. MPEP § 2164.01 states: “The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).”
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors, which have been outlined in the Federal Circuit decision of In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), include, but are not limited to, the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed. See also Ex parte Forman, 230 USPQ 546 (BPAI 1986).
Nature of the invention / Breadth of the claims
The nature of the claims at issue encompass methods of preventing or alleviating a HER2 positive tumor by a method comprising the steps of claim 1 (see claim 1 and its dependents).
State of the prior art / Predictability of the prior art
Clinical trials aimed at proving preventative cancer activity by a specific intervention are largely infeasible, due to the impossibly large number of subjects and an equally impossibly long timeframe. Although cancer is a common disease, specific types of cancer are still relatively infrequent events in an otherwise healthy population. Therefore, trials with cancer incidence as endpoints would necessarily involve several thousands of subjects followed for several decades. Such logistic difficulties have precluded cancer prevention trials with cancer incidence as an endpoint in all but a select few malignancies with treatments such as tamoxifen and finasteride (reviewed by Lee (Nature Reviews Cancer (2011) 11: 211-218), see page 211; Cancer Prevention Overview (PDQ®)–Patient Version, National Cancer Institute).
Working examples / Guidance in the specification
The specification discloses treating cancers that expresses HER2 with a HER2 bispecific antibody comprising a first light chain, a second light chain, a first heavy chain and a second heavy chain, wherein said first light chain and said second light chain is capable of assembling with a heavy chain of Pertuzumab and a heavy chain of Trastuzumab, respectively; wherein variable region of said first light chain and said second light chain comprises an amino acid sequence as set forth in SEQ ID NO: 7 which comprises the variable region of SEQ ID NO: 1 (see page 26).
While the specification does provide an exemplary embodiment of treating a cancer that expresses HER2 using with a HER2 bispecific antibody comprising a first light chain, a second light chain, a first heavy chain and a second heavy chain, wherein said first light chain and said second light chain is capable of assembling with a heavy chain of Pertuzumab and a heavy chain of Trastuzumab, respectively; wherein variable region of said first light chain and said second light chain comprises an amino acid sequence as set forth in SEQ ID NO: 1 and wherein variable region of said first heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 13 and variable region of said second heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 14, the disclosure does not provide a showing that such an antibody prevents or alleviates any cancer. Accordingly, one of skill in the art would be subject to undue and/or unreasonable experimentation to determine how to use the claimed antibodies to prevent cancer and alleviate cancer because the specification does not evidence that such antibodies would have these functions and the art does not evidence these functions in HER2 antibodies either.
Conclusion
Upon careful consideration of the factors used to determine whether undue experimentation is required, the amount of guidance, direction, and exemplification disclosed in the specification, as filed, is not deemed sufficient to have enable the skilled artisan to use the claimed invention at the time the application was filed to practice the full scope of the claims such as preventing or alleviating cancer without undue and/or unreasonable experimentation.
Applicant has submitted that claim 1 has been amended and the specification enables the claims as currently presented.
In response, the specification and the art does not provide evidence that HER2 antibodies are capable of preventing or alleviating cancer as detailed above. Notably, the tumor or cancer cell must first exist to be targeted by the antibody, so the antibody cannot prevent the cancer in a subject.
New Claim Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 9, 16, 19-20, 22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al (US 2019/0031782 A1, of record) and Clinical Trial NCT03619681 (version 4 from 10/31/2018, retrieved on 2/26/2026, https://clinicaltrials.gov/study/NCT03619681?tab=history&a=4#version-content-panel) as evidenced by Wei et al (Oncotarget, 8(31):51037-51049, 2017).
As evidenced by Wei et al, KN026 is a HER2 bispecific antibody derived from trastuzumab and pertuzumab (see page 51041).
Regarding claims 1, 19 and 22, Xu et al discloses methods of treating a breast cancer (breast cancer is a solid tumor as claimed in claim 19) that expresses HER2 by administering a HER2 bispecific antibody comprising a first light chain, a second light chain, a first heavy chain and a second heavy chain, wherein said first light chain and said second light chain is capable of assembling with a heavy chain of Pertuzumab and a heavy chain of Trastuzumab, respectively; wherein variable region of said first light chain and said second light chain comprises an amino acid sequence as set forth in SEQ ID NO: 1 which is 100% identical to instant SEQ ID NO:7 at doses of 20 mg/ml or 30 mg/ml (see pages 2-3, 14-16 and 21 and alignment).
RESULT 1
US-10-253-366-1
(NOTE: this sequence has 1268 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1, US/10253366
Publication No. US20030078388A1
GENERAL INFORMATION
APPLICANT: BASEY, CAROL D.
APPLICANT: BLANK, GREG S.
TITLE OF INVENTION: PROTEIN PURIFICATION
FILE REFERENCE: P1241R1
CURRENT APPLICATION NUMBER: US/10/253,366
CURRENT FILING DATE: 2002-09-24
PRIOR APPLICATION NUMBER: US/09/304,465
PRIOR FILING DATE: 1999-05-03
NUMBER OF SEQ ID NOS: 2
SEQ ID NO 1
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Sequence is synthesized.
Duplicate of:
US-15-541-921A-1
Filing date in PALM: 2017-07-06
Sequence 1, US/15541921A
Publication No. US20190031782A1
GENERAL INFORMATION
APPLICANT: SUZHOU ALPHAMAB CO., LTD
TITLE OF INVENTION: BISPECIFIC ANTIBODY OR ANTIIBODY MIXTURE WITH COMMON LIGHT CHAINS
FILE REFERENCE: IEC150074PCT
CURRENT APPLICATION NUMBER: US/15/541,921A
CURRENT FILING DATE: 2017-09-20
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 1
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 1110; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
With respect to claim 9, Xu et al discloses that the bispecific antibody further comprises a variable region of said first heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 13 and variable region of said second heavy chain comprises an amino acid sequence as set forth in instant SEQ ID NO: 14 and Fc regions of the Trastuzumab and Pertuzumab with knob and hole mutations which give the instant sequences of SEQ ID Nos: 15 and 16 of claim 9 (see pages 13-16 and alignments).
RESULT 1
US-09-811-123-2
(NOTE: this sequence has 411 duplicates in the database searched.
See complete list at the end of this report)
Sequence 2, US/09811123
Publication No. US20020001587A1
GENERAL INFORMATION
APPLICANT: Sharon Erickson
APPLICANT: Ralph Schwall
APPLICANT: Mark Sliwkowski
TITLE OF INVENTION: METHODS OF TREATMENT USING ANTI-ErbB
TITLE OF INVENTION: ANTIBODY-MAYTANSINOID CONJUGATES
FILE REFERENCE: GENENT.073A2
CURRENT APPLICATION NUMBER: US/09/811,123
CURRENT FILING DATE: 2001-03-16
PRIOR APPLICATION NUMBER: 60/238,327
PRIOR FILING DATE: 2000-10-05
PRIOR APPLICATION NUMBER: 09/602,530
PRIOR FILING DATE: 2000-06-23
NUMBER OF SEQ ID NOS: 11
SEQ ID NO 2
LENGTH: 119
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Humanized Antibody Sequence
US-15-541-921A-24
Filing date in PALM: 2017-07-06
Sequence 24, US/15541921A
Publication No. US20190031782A1
GENERAL INFORMATION
APPLICANT: SUZHOU ALPHAMAB CO., LTD
TITLE OF INVENTION: BISPECIFIC ANTIBODY OR ANTIIBODY MIXTURE WITH COMMON LIGHT CHAINS
FILE REFERENCE: IEC150074PCT
CURRENT APPLICATION NUMBER: US/15/541,921A
CURRENT FILING DATE: 2017-09-20
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 24
LENGTH: 119
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 634; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIY 60
Qy 61 NQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSS 119
RESULT 1
US-09-971-543-11
(NOTE: this sequence has 780 duplicates in the database searched.
See complete list at the end of this report)
Sequence 11, US/09971543
Publication No. US20020146846A1
GENERAL INFORMATION
APPLICANT: PLUCKTHUN, ANDREAS
APPLICANT: HONEGGER, ANNEMARIE
APPLICANT: WILLUDA, JORG
TITLE OF INVENTION: NOVEL METHOD FOR THE STABILIZATION OF CHIMERIC
TITLE OF INVENTION: IMMUNOGLOBULINS OR IMMUNOGLOBULIN FRAGMENTS, AND
TITLE OF INVENTION: STABILIZED ANTI-EGP-2 scFv FRAGMENT
FILE REFERENCE: PLUCK-3 CON
CURRENT APPLICATION NUMBER: US/09/971,543
CURRENT FILING DATE: 2001-10-04
PRIOR APPLICATION NUMBER: PCT/EP00/03176
PRIOR FILING DATE: 2000-04-10
PRIOR APPLICATION NUMBER: EP 99 10 7030.1
PRIOR FILING DATE: 1999-04-09
NUMBER OF SEQ ID NOS: 12
SEQ ID NO 11
LENGTH: 120
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic 4D5
peptide
US-15-541-921A-23
Filing date in PALM: 2017-07-06
Sequence 23, US/15541921A
Publication No. US20190031782A1
GENERAL INFORMATION
APPLICANT: SUZHOU ALPHAMAB CO., LTD
TITLE OF INVENTION: BISPECIFIC ANTIBODY OR ANTIIBODY MIXTURE WITH COMMON LIGHT CHAINS
FILE REFERENCE: IEC150074PCT
CURRENT APPLICATION NUMBER: US/15/541,921A
CURRENT FILING DATE: 2017-09-20
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 23
LENGTH: 120
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 645; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
With respect to claims 16, 20 and 24, Xu et al discloses that the breast cancer can be refractory to treatment (no longer responsive to conventional therapy) or metastatic (see page 2).
Xu et al does not disclose administering a HER2 antibody once every two weeks or once every three weeks (Q2W or Q3W).
Clinical Trial NCT03619681 discloses administering the KN026 HER2 bispecific antibody at a dose of 20 mg/kg to HER2 positive breast cancer patients at intervals of every week, every 2 weeks or every three weeks (see page 5)
Accordingly, it would have been prima facie obvious in the methods of Xu et al to administer the antibody once every two or three weeks because the antibody was being studied for administration every 2 weeks or every three weeks. Notably, this would be seen as combining prior art elements according to known methods to yield predictable results.
Furthermore, with respect to the interval of administration, the art taught that the interval could be varied and determined, so the interval was recognized as a variable which achieves a recognized result and as set forth in MPEP 2144.05: “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. In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977).
It is a common objective in the art to optimize result effective variables, so as achieve optimal effect and maximal benefit. See In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) (“[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” (citations omitted)). Therefore, the optimization of the interval would be seen as routine optimization, absent a showing otherwise. Furthermore, one of skill in the art would have expected success in practicing such methods because the antibody would be expected to treat HER2 expressing cancers.
Accordingly, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
Claims 1, 9, 16, 19-20, 22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al (US 2019/0031782 A1, of record) and WO 2016/022723 A1 (Geretti et al).
Regarding claims 1, 19 and 22, Xu et al discloses methods of treating a breast cancer (breast cancer is a solid tumor as claimed in claim 19) that expresses HER2 by administering a HER2 bispecific antibody comprising a first light chain, a second light chain, a first heavy chain and a second heavy chain, wherein said first light chain and said second light chain is capable of assembling with a heavy chain of Pertuzumab and a heavy chain of Trastuzumab, respectively; wherein variable region of said first light chain and said second light chain comprises an amino acid sequence as set forth in SEQ ID NO: 1 which is 100% identical to instant SEQ ID NO:7 at doses of 20 mg/ml or 30 mg/ml (see pages 2-3, 14-16 and 21 and alignment).
RESULT 1
US-10-253-366-1
(NOTE: this sequence has 1268 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1, US/10253366
Publication No. US20030078388A1
GENERAL INFORMATION
APPLICANT: BASEY, CAROL D.
APPLICANT: BLANK, GREG S.
TITLE OF INVENTION: PROTEIN PURIFICATION
FILE REFERENCE: P1241R1
CURRENT APPLICATION NUMBER: US/10/253,366
CURRENT FILING DATE: 2002-09-24
PRIOR APPLICATION NUMBER: US/09/304,465
PRIOR FILING DATE: 1999-05-03
NUMBER OF SEQ ID NOS: 2
SEQ ID NO 1
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Sequence is synthesized.
Duplicate of:
US-15-541-921A-1
Filing date in PALM: 2017-07-06
Sequence 1, US/15541921A
Publication No. US20190031782A1
GENERAL INFORMATION
APPLICANT: SUZHOU ALPHAMAB CO., LTD
TITLE OF INVENTION: BISPECIFIC ANTIBODY OR ANTIIBODY MIXTURE WITH COMMON LIGHT CHAINS
FILE REFERENCE: IEC150074PCT
CURRENT APPLICATION NUMBER: US/15/541,921A
CURRENT FILING DATE: 2017-09-20
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 1
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 1110; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
With respect to claim 9, Xu et al discloses that the bispecific antibody further comprises a variable region of said first heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 13 and variable region of said second heavy chain comprises an amino acid sequence as set forth in instant SEQ ID NO: 14 and Fc regions of the Trastuzumab and Pertuzumab with knob and hole mutations which give the instant sequences of SEQ ID Nos: 15 and 16 of claim 9 (see pages 13-16 and alignments).
RESULT 1
US-09-811-123-2
(NOTE: this sequence has 411 duplicates in the database searched.
See complete list at the end of this report)
Sequence 2, US/09811123
Publication No. US20020001587A1
GENERAL INFORMATION
APPLICANT: Sharon Erickson
APPLICANT: Ralph Schwall
APPLICANT: Mark Sliwkowski
TITLE OF INVENTION: METHODS OF TREATMENT USING ANTI-ErbB
TITLE OF INVENTION: ANTIBODY-MAYTANSINOID CONJUGATES
FILE REFERENCE: GENENT.073A2
CURRENT APPLICATION NUMBER: US/09/811,123
CURRENT FILING DATE: 2001-03-16
PRIOR APPLICATION NUMBER: 60/238,327
PRIOR FILING DATE: 2000-10-05
PRIOR APPLICATION NUMBER: 09/602,530
PRIOR FILING DATE: 2000-06-23
NUMBER OF SEQ ID NOS: 11
SEQ ID NO 2
LENGTH: 119
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Humanized Antibody Sequence
US-15-541-921A-24
Filing date in PALM: 2017-07-06
Sequence 24, US/15541921A
Publication No. US20190031782A1
GENERAL INFORMATION
APPLICANT: SUZHOU ALPHAMAB CO., LTD
TITLE OF INVENTION: BISPECIFIC ANTIBODY OR ANTIIBODY MIXTURE WITH COMMON LIGHT CHAINS
FILE REFERENCE: IEC150074PCT
CURRENT APPLICATION NUMBER: US/15/541,921A
CURRENT FILING DATE: 2017-09-20
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 24
LENGTH: 119
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 634; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTDYTMDWVRQAPGKGLEWVADVNPNSGGSIY 60
Qy 61 NQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQRFKGRFTLSVDRSKNTLYLQMNSLRAEDTAVYYCARNLGPSFYFDYWGQGTLVTVSS 119
RESULT 1
US-09-971-543-11
(NOTE: this sequence has 780 duplicates in the database searched.
See complete list at the end of this report)
Sequence 11, US/09971543
Publication No. US20020146846A1
GENERAL INFORMATION
APPLICANT: PLUCKTHUN, ANDREAS
APPLICANT: HONEGGER, ANNEMARIE
APPLICANT: WILLUDA, JORG
TITLE OF INVENTION: NOVEL METHOD FOR THE STABILIZATION OF CHIMERIC
TITLE OF INVENTION: IMMUNOGLOBULINS OR IMMUNOGLOBULIN FRAGMENTS, AND
TITLE OF INVENTION: STABILIZED ANTI-EGP-2 scFv FRAGMENT
FILE REFERENCE: PLUCK-3 CON
CURRENT APPLICATION NUMBER: US/09/971,543
CURRENT FILING DATE: 2001-10-04
PRIOR APPLICATION NUMBER: PCT/EP00/03176
PRIOR FILING DATE: 2000-04-10
PRIOR APPLICATION NUMBER: EP 99 10 7030.1
PRIOR FILING DATE: 1999-04-09
NUMBER OF SEQ ID NOS: 12
SEQ ID NO 11
LENGTH: 120
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic 4D5
peptide
US-15-541-921A-23
Filing date in PALM: 2017-07-06
Sequence 23, US/15541921A
Publication No. US20190031782A1
GENERAL INFORMATION
APPLICANT: SUZHOU ALPHAMAB CO., LTD
TITLE OF INVENTION: BISPECIFIC ANTIBODY OR ANTIIBODY MIXTURE WITH COMMON LIGHT CHAINS
FILE REFERENCE: IEC150074PCT
CURRENT APPLICATION NUMBER: US/15/541,921A
CURRENT FILING DATE: 2017-09-20
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 23
LENGTH: 120
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 645; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
With respect to claims 16, 20 and 24, Xu et al discloses that the breast cancer can be refractory to treatment (no longer responsive to conventional therapy) or metastatic (see page 2).
Xu et al does not disclose administering a HER2 antibody once every two weeks or once every three weeks (Q2W or Q3W).
Geretti et al discloses administering the HER2 antibody, trastuzumab every two weeks or every three weeks (see pages 28-29).
Accordingly, it would have been prima facie obvious in the methods of Xu et al to administer the bispecific antibody which is partially derived from trastuzumab every 2 weeks or every three weeks because one would expect the bispecific antibody to also be effective when administered every two weeks or every three weeks. Notably, this would be seen as combining prior art elements according to known methods to yield predictable results.
Furthermore, with respect to the interval of administration, the art taught that the interval could be varied and determined, so the interval was recognized as a variable which achieves a recognized result and as set forth in MPEP 2144.05: “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. In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977).
It is a common objective in the art to optimize result effective variables, so as achieve optimal effect and maximal benefit. See In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980) (“[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” (citations omitted)). Therefore, the optimization of the interval would be seen as routine optimization, absent a showing otherwise. Furthermore, one of skill in the art would have expected success in practicing such methods because the antibody would be expected to treat HER2 expressing cancers.
Accordingly, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner works a flexible schedule.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
February 26, 2026