Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant’s election without traverse of Group II, claims 84-123 in the reply filed on January 16, 2026 is acknowledged.
Applicant’s election without traverse of species: i) the ADC of Trastuzumab Deruxtecan (DS-8201); and ii) breast cancer, which reads on claims 84-101, 103-121,and 123, in the reply filed on January 16, 2026 is acknowledged.
Claims 1, 21, 41, 62, and 84-123 are pending.
Claims 1, 21, 41, 62, 102, and 122 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 84-101, 103-121, and 123 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of International Application of PCT/IB2021/058273 filed September 11, 2021, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/077,604 filed September 12, 2020. The priority date has been established as September 12, 2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 03/11/2023 and 11/26/2025 have been considered and entered by examiner.
Claim Rejections - 35 USC § 112
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 87-90, 109, 110 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 87 recites the limitation "wherein the staining intensity of each cytoplasm" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim.
Claim 89 depending on claim 88, recites “
a
k
l
r
j
-
r
i
=
A
k
l
*
e
x
p
(
-
r
j
-
r
i
/
r
n
o
r
m
)
with predefined constant coefficients
A
00
,
A
10
,
A
01
,
A
11
,
A
20
,
A
02
” which lacks antecedent basis for
a
10
r
j
-
r
i
and
a
01
r
j
-
r
i
and renders the claim indefinite. Claim 88 recites only functions of
a
00
,
a
11
,
a
20
,
a
02
. It is unclear how the predefined constant coefficients
A
10
,
A
01
, and functions
a
10
r
j
-
r
i
and
a
01
r
j
-
r
i
are used in the claimed method.
Claim 90 also recites
A
10
,
A
01
. As set forth above, is unclear how the predefined constant coefficients
A
10
,
A
01
, and functions
a
10
r
j
-
r
i
and
a
01
r
j
-
r
i
are used in the claimed method.
Claim 109 depending on claim 108, recites “
a
k
l
r
j
-
r
i
=
A
k
l
*
e
x
p
(
-
r
j
-
r
i
/
r
n
o
r
m
)
with predefined constant coefficients
A
00
,
A
10
,
A
01
,
A
11
,
A
20
,
A
02
” which lacks antecedent basis for
a
10
r
j
-
r
i
and
a
01
r
j
-
r
i
and renders the claim indefinite. Claim 108 recites only functions of
a
00
,
a
11
,
a
20
,
a
02
. It is unclear how the predefined constant coefficients
A
10
,
A
01
, and functions
a
10
r
j
-
r
i
and
a
01
r
j
-
r
i
are used in the claimed method.
Claim 110 also recites
A
10
,
A
01
. As set forth above, is unclear how the predefined constant coefficients
A
10
,
A
01
, and functions
a
10
r
j
-
r
i
and
a
01
r
j
-
r
i
are used in the claimed method.
Claim 88 is also rejected because it depends on claim 87.
Claim Rejections - 35 USC § 112
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 84-101, 103-121, and 123 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The instant claims are drawn to a method of treating cancer involving administering to a cancer patient an antibody drug conjugate (ADC) that includes an ADC payload and an ADC antibody that targets a protein on a cancer cell, wherein the protein is human epidermal growth factor receptor 2 (HER2), the method comprising: staining a tissue sample of the cancer patient immunohistochemically using a dye linked to a diagnostic antibody, wherein the diagnostic antibody binds to the protein on the cancer cells in the tissue sample; acquiring a digital image of the tissue sample; detecting cancer cells in the digital image; computing for each cancer cell a single-cell ADC score based on the staining intensities of the dye in the membrane; generating a treatment score by aggregating all single-cell ADC scores of the tissue sample using a statistical operation; and administering a therapy involving the ADC to the cancer patient if the treatment score exceeds a predetermined threshold (claim 84),
or a method of treating cancer involving administering to a cancer patient an antibody drug conjugate (ADC) that includes an ADC payload and an ADC antibody that targets a protein on a cancer cell, wherein the protein is human epidermal growth factor receptor 2 (HER2), the method comprising: administering a therapy involving the ADC to the cancer patient if a response score exceeds a predetermined threshold, wherein the response score was generated by aggregating single-cell ADC scores of a tissue sample of the cancer patient using a statistical operation, wherein each single-cell ADC score was computed for each cancer cell based on staining intensity of a dye in the membrane, wherein the cancer cells were detected in a digital image of the tissue sample of the cancer patient, wherein the tissue sample was immunohistochemically stained using the dye linked to a diagnostic antibody, and wherein the diagnostic antibody binds to the protein on the cancer cells in the tissue sample (claim 104). Thus, the claims encompass unlimited number of ways to generate single-cell ADC score and/or response score (as evidenced by claims 88-90 and 108-110). Other than general description of several possible mathematical formula, the specification only provides very limited working examples for specific methods (e.g. HER2+ cell density; neighborhood scores with
d
=
20
o
r
25
μm) for generating single-cell ADC scores and response scores for one ADC: Trastuzumab deruxtecan (e.g. Figs 33-41, [0178-0187] of the instant publication US 2024/0301512 A1). Thus, the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed".
Even for claims 88-90 and 108-110, which limit the method of generating a single cell ADC score, the method would encompass: 1) unlimited options of
d
(distance); 2) unlimited options for functions of
a
00
,
a
11
,
a
20
,
a
02
; 3) unlimited options for predefined constant coefficients
A
00
,
A
11
,
A
20
,
A
02
. In addition, because different ADCs would have different physical/chemical properties such as stability and/or permeability, different ADCs may have different therapeutic activities to the neighboring cells. Thus, the choices of distance (unlimited), functions (unlimited) and coefficients (unlimited) need to be tested and optimized for each cancer (unlimited), for each ADC (unlimited), for each different cohort of training patients, as evidenced by claims 90 and 110.
In view of above, Fig. 34 of the instant specification describes “QCS Positive” if at least 90% of cell exhibit an optical density of HER2 membrane staining above an optical density cut-off of 0.0365; Figs. 35 and 36 shows that patients with more than 95% of cells had an optical density above a cut-off of 0.04077 or within a minimum distance (20 μm) of a positive cells have higher survival probability ([0187], [0188]); Fig. 38 uses HER2-positve cell density and a neighborhood score based on a distance of 25 μm to ([0195]); Fig. 39 uses HER2-positve cell density and a neighborhood score based on a distance of 20 μm, the distance dependent weighting is calculated by
e
x
p
(
-
0.5
*
(
d
i
s
t
/
s
i
g
m
a
)
^
2
)
([0196]). It is noted that the function used for Fig. 39 is different from the function recited by claims 88, 89, 108 or 109. Figs. 40 and 41 uses HER2-positve cell density and a neighborhood score based on a distance of 20 μm ([0197], [0198]). All results are based on the same ADC: Trastuzumab deruxtecan. Taken together, the specification mainly describes methods of select patient population based on HER2-positive cell density and a neighborhood score based on the total number of cells within 20 μm or 25 μm of HER2-positive cells. Based on the limited examples presented in the specification, one of ordinary skilled in the art would not be able to readily visualize/recognize the optimal score generating methods from unlimited choices of distances, functions and/or coefficients and unlimited choices of ADCs & cancers encompassed by the claims (e.g. claims 88 and 108).
As set forth above, one of ordinary in the art would have known: 1) various factors (e.g. type of ADC, type of cancer) would impact the method of generating the single cell ADC scores and/or response scores; 2) unlimited choices of functions, coefficient and distance need to be tested and optimized for each cancer cell and each ADC. The specification has not established the structure and function relationship between the encompassed scoring methods for predicting response to all ADC drugs in all cancers encompassed by the claims. As a result, the ordinary artisan could reasonably conclude based on a survey of the data shown in the instant specification in support of the breadth and scope of the instant claimed methods that Applicants were not in possession of the claimed methods. Taken together, the instant specification has not provided a sufficient description for the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 84-87, 91-101, 103-107, 111-121, and 123 are rejected under 35 U.S.C. 103 as being unpatentable over Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) in view of Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
Regarding generating a score to predict a response of a cancer patient to a therapy targeting HER2 of claims 84 and 104, Chukka teaches “The present disclosure provides systems and methods for detecting genetic aberrations (e.g. high copy numbers or chromosomal abnormalities) within cells, such as cells which are automatically selected for assessment. In some embodiments, the cells which are automatically selected for assessment are located within tumor tissue regions which comprise cells meeting predetermined protein biomarker staining criteria. By automatically selecting cells for assessment, subjectivity is reduced or eliminated. It is believed that the automated systems and methods described herein enable improved patient outcome and an improved selection of therapeutic regimens since the disclosed systems and methods comparatively utilize additional data as compared with manual analysis methods” ([0051]). While examples herein may refer to specific tissues and/or the application of specific stains or detection probes for the detection of certain biomarkers (and hence diseases), the skilled artisan will appreciate that different tissues and different stains/detection probes may be applied to detect different markers and different diseases. For example, although certain examples may refer to quantifying amounts of signals corresponding to the HER2 ([0052]). In the context of HER2 status for breast and/or gastric cancers, the need for accurate determination of HER2 status is illustrated by the excellent results of therapies targeting HER2 in the clinic. Trastuzumab and lapatinib are well-tolerated in patients with little toxicity, since its effects are relatively specific for cancer cells overexpressing HER2. As such, determining whether HER2 status of a breast or gastric cancer is an important step in deciding on a treatment plan ([0053]).
Regarding “staining a tissue sample immunohistochemically using a dye linked to a diagnostic antibody, wherein the diagnostic antibody binds to the protein on the cancer cells in the tissue sample”, Chukka teaches that the biological sample may be stained through application of one or more stains, and the resulting image or image data comprises signals corresponding to each of the one or more stains. In some embodiments, the input images are simplex images having only a single stain (e.g., stained with 3,3'-diaminobenzidine (DAB)). In some embodiments, the biological sample may be stained in a multiplex assay for two or more stains (thus providing multiplex images). In some embodiments, the biological samples are stained for the presence of at least one protein biomarker and at least two nucleic acid biomarkers (e.g. DNA, RNA, microRNAs, etc.) ([0073]). In some embodiments, the biological samples are stained in an immunohistochemistry assay for the presence of one or more protein biomarkers. For example, the biological sample may be stained for the presence of a human epidermal growth factor receptor 2 protein (HER2 protein). Currently in the United States, there are two Food and Drug Administration (FDA) approved methods for HER2 assessment: HerceptTest™ (DAKO, Glostrup Denmark) and HER2/neu (4B5) rabbit monoclonal primary antibody (Ventana, Tucson, Arizona) ([0074])
Regarding “acquiring a digital image of the tissue sample; detecting cancer cells in the digital image”, Chukka teaches that in some embodiments, and with reference to FIG. 2, the digital pathology system 200 runs an imaging module 202 to capture images or image data (such as from a scanning device 12) of a biological sample having one or more stains (step 310; see also step 410). In some embodiments, the images received or acquired are RGB images or multispectral images (e.g. multiplex brightfield and/or dark field images). In some embodiments, the images captured are stored in memory 201 ([0071]).
Regarding “computing for each cancer cell a single-cell ADC score based on staining intensities of the dye in the membrane the cancer cell; and generating the treatment score by aggregating all single-cell ADC scores of the tissue sample using a statistical operation”. Chukka teaches that in some embodiments, utilizes data acquired during the detection and classification of cells. For example, the cell detection and classification module 204 may comprise a series of image analysis algorithms and may be used to determine a presence of one or more of a nucleus, a cell wall, a tumor cell, or other structures within the identified cell clusters, as described herein ([0123]). In some embodiments, the expression score is an H-score. In some embodiments, the Ή' score is used to assess the percentage of tumor cells with cell membrane staining graded as 'weak,' 'moderate' or 'strong.' The grades are summated to give an overall maximum score of 300 and a cut-off point of 100 to distinguish between a 'positive' and 'negative.' For example, a membrane staining intensity (0, 1+, 2+, or 3+) is determined for each cell in a fixed field of view (or here, each cell in a tumor or cell cluster). The H-score may simply be based on a predominant staining intensity, or more complexly, can include the sum of individual H-scores for each intensity level seen. By one method, the percentage of cells at each staining intensity level is calculated, and finally, an H-score is assigned using the following formula: [1 x (% cells 1+) + 2 x (% cells 2+) + 3 x (% cells 3+)]. The final score, ranging from 0 to about 300, provides more relative weight to higher-intensity membrane staining in a given tumor sample. The sample can then be considered positive or negative on the basis of a specific discriminatory threshold. Additional methods of calculating an H-score are described in United States Patent Publication 2015/0347702, the disclosure of which is hereby incorporated by reference herein in its entirety ([0125]). In other embodiments, the expression score is an immunohistochemistry combination score, which is a prognostic score based on a number of IHC markers, wherein the number of markers is greater than one. Such combination scores are described in US Patent Publication No. 2017/0082627, the disclosure of which is hereby incorporated by reference herein in its entirety ([0128]). Thus, the value of 0, 1+, 2+, or 3+ on the intensity of staining for cancer cells would read on a single-cell ADC score, and the H-score reads on the treatment score aggregated from all single ADC scores of the instant application.
Chukka teaches that determining the status of HER2 expression is important for develop HER2 targeting therapy ([0053] and [0054]).
Chukka teaches as set forth above, however, Chukka does not teach administering a HER2 targeting ADC based on a score based on HER2 staining.
Keam teaches that Trastuzumab deruxtecan, a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate, is being developed for the treatment of HER2-expressing solid tumors, including breast cancer (Abstract).
Keam teaches that Trastuzumab deruxtecan is approved in the USA for treatment of HER2-positive breast cancers who have received two or more prior treatments and is under regulatory review in Japan for HER2-positive metastatic breast cancer (2nd paragraph of Introduction).
Keam teaches that Trastuzumab deruxtecan can be used for HER2-positive metastatic breast cancers, HER2-low metastatic breast cancers, HER2-positive advanced gastric cancer, HER2-expressing advanced colorectal cancer and metastatic nonsquamous HER2-overexpressing or mutated non-small cell lung cancer (1st paragraph of Introduction).
Keam teaches that Trastuzumab deruxtecan consists of a humanized, anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab (and which therefore binds to HER2 on tumor cells), covalently linked to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. Deruxtecan consists of a protease-cleavable maleimide tetrapeptide linker and DXd. Delivery of the ADC payload (i.e. DXd) directly to HER2-expressing tumor cells minimizes exposure of the cytotoxic agent to normal cells (1st paragraph of Introduction).
As evidenced by Fig. 22 and § 4.3.3 of Singh, antibody was conjugated via a thioether bond though cysteine and the structure of Trastuzumab deruxtecan reads on the structure of 99 and 119.
As evidenced by Robblee (shown below), the heavy chain and light chain sequences of Trastuzumab reads on the sequences of claims 100, 101, 103, 120, 121, and 123.
Trastuzumab has a heavy chain variable region of SEQ ID NO: 10 (recited CDRs were underlined):
US-14-403-811-1
Query Match 100.0%; Score 645; DB 1; Length 450;
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
Trastuzumab has a light chain variable region of SEQ ID NO: 11(recited CDRs were underlined):
US-14-403-811-2
Query Match 100.0%; Score 557; DB 1; Length 214;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK 107
Trastuzumab has a heavy chain of SEQ ID NO: 2
US-14-403-811-1
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Trastuzumab has a light chain of SEQ ID NO: 3
US-14-403-811-2
Query Match 100.0%; Score 1110; DB 1; 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
Taken together, Trastuzumab deruxtecan would read on the ADC of claims 84, 92-94, 99-101, 103, 104, 112-114, 119-121, and 123.
Keam teaches that Trastuzumab deruxtecan shows activities in multiple clinical trials for various HER2-expressing cancers (§ 2.3 Therapeutic Trials; and Table on page 506), including cancers resistant to trastuzumab emtansine and low HER2 expression cancer (page 503, col. 1, para. 4).
Keam teaches a HER2-low companion diagnostic test that will use the VENTANA HER2 (4B5) assay to identify patients with cancers for Trastuzumab deruxtecan (§ 3 Current Status, on page 507).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of Chukka and Keam to develop a method for treating cancers (e.g. breast cancer) comprising the steps of determining the status of HER2 in cancer cells and choosing the patients with optimal H-score of HER2 expression as taught by Chukka, and administering the patients with Trastuzumab deruxtecan because Trastuzumab deruxtecan show good therapeutic activity for HER2 expression cancers (including breast cancer) and approved by FDA for cancer therapy. One of ordinary skilled in the art would have a reasonable expectation of success because in the method of Chukka enables improved patient outcome and an improved selection of therapeutic regimens and Trastuzumab deruxtecan of Keam is well-known, widely-tested and approved for cancer therapy. The motivation would have been to better select a patient population for a HER2-targeting therapy and to expand the treatment to more patients including patients with low HER2 expression.
Regarding claims 85, 86, 105 and 106, Chukka teaches that cytoplasmic staining pattern are also analyzed and methods of identifying, classifying of cell membrane and cell cytoplasm images ([0102], [0103]). For example, US 7,760,927 describes an automated method for simultaneously identifying a plurality of pixels in an input image of a biological tissue stained with a biomarker, including considering a first color plane of a plurality of pixels in a foreground of the input image for simultaneous identification of cell cytoplasm and cell membrane pixels, wherein the input image has been processed to remove background portions of the input image and to remove counterstained components of the input image; determining a threshold level between cell cytoplasm and cell membrane pixels in the foreground of the digital image; and determining simultaneously with a selected pixel and its eight neighbors from the foreground if the selected pixel is cell cytoplasm pixel, a cell membrane pixel or a transitional pixel in the digital image using the determined threshold level ([0103]).
Regarding claims 87, 96, 107 and 116, Chukka teaches that images have a stain of 3,3’-diaminobenzidine (DAB) ([0073], [0079]). An input image stained for the presence of HER2 would have signals corresponding to HER2 DAB membrane staining ([0086]). And pixels of image are retrieved and analyzed to get the DAB staining data ([0088]).
Regarding claims 91 and 111, Chukka teaches 'H' score is used to assess the percentage of tumor cells with cell membrane staining graded as 'weak,' 'moderate' or 'strong.' The grades are summated to give an overall maximum score of 300 and a cut-off point of 100 to distinguish between a 'positive' and 'negative.' For example, a membrane staining intensity (0, 1 +, 2+, or 3+) is determined for each cell in a fixed field of view (or here, each cell in a tumor or cell cluster). By one method, the percentage of cells at each staining intensity level is calculated, and finally, an H-score is assigned using the following formula: [1 x (% cells 1+) + 2 x (% cells 2+) + 3 x (% cells 3+)]. The final score, ranging from 0 to about 300, provides more relative weight to higher-intensity membrane staining in a given tumor sample. This reads on the determining a quantile with a predefined percentage. In addition, one of ordinary skilled would know to use the basic statistic measurements such as means, median to compare with negative and positive control values through routine practice.
Regarding claims 94 and 114, Keam teaches that Trastuzumab deruxtecan, a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate (Abstract).
Regarding claims 95 and 115, Chukka teaches using Ventana HER2 (4B5) as diagnostic antibody for HER2 ([0074], and Fig. 12). In addition, Keam teaches a HER2-low companion diagnostic test that will use the VENTANA HER2 (4B5) assay for Trastuzumab deruxtecan,
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.
U.S. Patent No. 10,155,821
Claims 84-87, 91-101, 103-107, 111-121, and 123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,155,821 B2 (hereinafter Pat. 821, Appl. No. 15/221,851) in view of Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) and Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
The claims of Pat. 821 teach an ADC with a drug component which is the same as the drug component of Trastuzumab deruxtecan (claim 1).
The claims of Pat. 821 teach that the antibody component of the ADC is an anti-HER2 antibody comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2 (claim 8). As shown below,
Trastuzumab has a heavy chain of SEQ ID NO: 1 of Pat. 821.
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Trastuzumab has a light chain of SEQ ID NO: 2 of Pat. 821:
Query Match 100.0%; Score 1110; DB 1; 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
Taken together, the claims of Pat. 821 teach the ADC with the same drug component and the same antibody component as Trastuzumab deruxtecan, as evidenced by Singh and Robblee.
The claims of Pat. 821 do not teach the method of treating cancers (such as breast cancer) with the ADC and the method of generating response scores as instantly claimed.
As set forth above in 103 rejection, Chukka teaches methods of generating single cell ADC scores and response scores based on antibody staining, image capture, image analysis, cancer cell identification and statistical analysis. Chukka teaches that the method are more objective and would help to identify patients for HER2-targeting therapies. Keam teaches that Trastuzumab deruxtecan is approved in the USA for cancer treatment and Trastuzumab deruxtecan can be used for HER2-positive metastatic breast cancers, HER2-low metastatic breast cancers, HER2-positive advanced gastric cancer, HER2-expressing advanced colorectal cancer and metastatic nonsquamous HER2-overexpressing or mutated non-small cell lung cancer. It is noted that Trastuzumab deruxtecan would read on the ADC of Pat. 821, as evidenced by Singh and Robblee,.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 821, Chukka and Keam to treat cancer patients (e.g. breast cancer) with Trastuzumab deruxtecan taught by Pat. 821 and Keam because Trastuzumab deruxtecan has been approved for breast cancer treatment and has shown therapeutic activity to various cancers and to add a step of determining response score based on the method taught by Chukka. One of ordinary skilled in the art would have had a reasonable expectation that the modified method would lead to better therapeutic outcome, because the HER2-status is critical for a HER2-targeting therapy, the method taught by Chukka provides a more objective evaluation about the HER2 status. The motivation would have been to identify a suitable patient population for Trastuzumab deruxtecan and to expand the therapy to some HER2-low expression patients.
U.S. Patent No. 11,795,236
Claims 84-87, 91-101, 103-107, 111-121, and 123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,795,236 B2 (hereinafter Pat. 236, Appl. No. 16/130,615) in view of Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) and Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
It is noted that Pat. 236 is a divisional application of Pat. 821. Thus, they share the same disclosure including sequence list.
The claims Pat. 236 teach a method of treating HER2-low expressing cancers including breast cancer with an ADC, wherein the ADC has a drug component which is the same as the drug component of Trastuzumab deruxtecan (claims 1 and 7).
The claims of Pat. 236 teach that the antibody component of the ADC is an anti-HER2 antibody comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2 (claims 4 and 8). As set forth above, Trastuzumab has the heavy chain and light chain of SEQ ID NO: 1 and SEQ ID NO:2, respectively.
Taken together, the claims of Pat. 236 teach treating HER2-low expression cancers using an ADC with the same drug component and the same antibody component as Trastuzumab deruxtecan, as evidenced by Singh and Robblee.
The claims of Pat. 236 do not teach the method also comprising generating response scores as instantly claimed.
As set forth above in 103 rejection, Chukka teaches methods of generating single cell ADC scores and response scores based on antibody staining, image capture, image analysis, cancer cell identification and statistical analysis. Chukka teaches that the method are more objective and would help to identify patients for HER2-targeting therapies. Keam teaches that Trastuzumab deruxtecan is approved in the USA for cancer treatment and Trastuzumab deruxtecan can be used for HER2-positive metastatic breast cancers, HER2-low metastatic breast cancers, HER2-positive advanced gastric cancer, HER2-expressing advanced colorectal cancer and metastatic nonsquamous HER2-overexpressing or mutated non-small cell lung cancer. It is noted that Trastuzumab deruxtecan would read on the ADC of Pat. 236, as evidenced by Singh and Robblee.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 236, Chukka and Keam to treat cancer patients (e.g. HER2-low expression breast cancer) with Trastuzumab deruxtecan taught by Pat. 236 and Keam because Trastuzumab deruxtecan has been approved for breast cancer treatment and has shown therapeutic activity to various cancers, and to add a step of determining response score based on the method taught by Chukka. One of ordinary skilled in the art would have had a reasonable expectation that the modified method would lead to better therapeutic outcome, because the HER2-status is critical for a HER2-targeting therapy, the method taught by Chukka provides a more objective evaluation about the HER2 status. The motivation would have been to identify a suitable patient population for Trastuzumab deruxtecan and to expand the therapy to some HER2-low expression patients.
Application No. 16/334,008
Claims 84-87, 91-101, 103-107, 111-121, and 123 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37, 40-51, 57-60, 62, 64, 65, 72, 73, 79, 80, 83 and 84 of copending Application No. 16/334,008 (hereinafter Appl. 008) in view of Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) and Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
This is a provisional nonstatutory double patenting rejection.
The claims Appl. 008 teach a method of treating HER2 expressing cancers having resistance to an existing anti-HER2 drug with an ADC, wherein the ADC has a drug component which is the same as the drug component of Trastuzumab deruxtecan (claim 37), wherein the cancer can be breast cancer (claim 59), or gastric cancer (claim 60).
The claims Appl. 008 teach that the antibody component of the ADC is an anti-HER2 antibody comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2 (claims 83 and 84). As set forth above, Trastuzumab has the heavy chain and light chain of SEQ ID NO: 1 and SEQ ID NO:2, respectively.
As shown below,
Trastuzumab has a heavy chain of SEQ ID NO: 1 of Appl. 008:
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Trastuzumab has a light chain of SEQ ID NO: 2 of Appl. 008:
Query Match 100.0%; Score 1110; DB 1; 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
Taken together, the claims of Appl. 008 teach the ADC with the same drug component and the same antibody component as Trastuzumab deruxtecan, as evidenced by Singh and Robblee.
The claims of Appl. 008 do not teach the method also comprising generating response scores as instantly claimed.
As set forth above in 103 rejection, Chukka teaches methods of generating single cell ADC scores and response scores based on antibody staining, image capture, image analysis, cancer cell identification and statistical analysis. Chukka teaches that the method are more objective and would help to identify patients for HER2-targeting therapies. Keam teaches that Trastuzumab deruxtecan is approved in the USA for cancer treatment and Trastuzumab deruxtecan shows activity to cancer resistant to trastuzumab emtansine. It is noted that Trastuzumab deruxtecan would read on the ADC of Appl. 008, as evidenced by Singh and Robblee,.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 008, Chukka and Keam to treat cancer patients (e.g. cancers resistant to trastuzumab emtansine) with Trastuzumab deruxtecan taught by Appl. 008 and Keam because Trastuzumab deruxtecan has been approved for cancer treatment and has shown therapeutic activity to various cancers including cancers resistant to trastuzumab emtansine, and to add a step of determining response score based on the method taught by Chukka. One of ordinary skilled in the art would have had a reasonable expectation that the modified method would lead to better therapeutic outcome, because the HER2-status is critical for a HER2-targeting therapy, the method taught by Chukka provides a more objective evaluation about the HER2 status. The motivation would have been to identify a suitable patient population for Trastuzumab deruxtecan and to expand the therapy to trastuzumab emtansine-resistant, HER2-expressing patients.
Application No. 16/640,914
Claims 84-87, 91-101, 103-107, 111-121, and 123 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-10, and 44 of copending Application No. 16/640,914 (hereinafter Appl. 914) in view of Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) and Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
This is a provisional nonstatutory double patenting rejection.
The claims Appl. 914 teach an ADC which has a drug component which is the same as the drug component of Trastuzumab deruxtecan (claim 1), and the drug component is connected with an antibody through a thioether bond (claim 1).
The claims Appl. 914 teach that the antibody component of the ADC is an anti-HER2 antibody comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2 (claims 7-9).
As shown below, Trastuzumab has the heavy chain and light chain of SEQ ID NO: 1 and SEQ ID NO:2, respectively.
Trastuzumab has a heavy chain of SEQ ID NO: 1 of Appl. 914:
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Trastuzumab has a light chain of SEQ ID NO: 2 of Appl. 914:
Query Match 100.0%; Score 1110; DB 1; 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
Taken together, the claims of Appl. 914 teach the ADC with the same drug component and the same antibody component as Trastuzumab deruxtecan, as evidenced by Singh and Robblee.
The claims Appl. 914 teach treating cancer with the pharmaceutical composition comprising the ADC (claim 44).
The claims of Appl. 914 do not teach the method also comprising generating response scores for the cancer patients as instantly claimed.
As set forth above in 103 rejection, Chukka teaches methods of generating single cell ADC scores and response scores based on antibody staining, image capture, image analysis, cancer cell identification and statistical analysis. Chukka teaches that the method are more objective and would help to identify patients for HER2-targeting therapies. Keam teaches that Trastuzumab deruxtecan is approved in the USA for cancer treatment and Trastuzumab deruxtecan can be used for HER2-positive metastatic breast cancers, HER2-low metastatic breast cancers, HER2-positive advanced gastric cancer, HER2-expressing advanced colorectal cancer and metastatic nonsquamous HER2-overexpressing or mutated non-small cell lung cancer. It is noted that Trastuzumab deruxtecan would read on the ADC of Appl. 914, as evidenced by Singh and Robblee.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 914, Chukka and Keam to treat cancer patients (e.g. HER2-low expression breast cancer) with Trastuzumab deruxtecan taught by Appl. 914 and Keam because Trastuzumab deruxtecan has been approved for breast cancer treatment and has shown therapeutic activity to various cancers, and to add a step of determining response score based on the method taught by Chukka. One of ordinary skilled in the art would have had a reasonable expectation that the modified method would lead to better therapeutic outcome, because the HER2-status is critical for a HER2-targeting therapy, the method taught by Chukka provides a more objective evaluation about the HER2 status. The motivation would have been to identify a suitable patient population for Trastuzumab deruxtecan and to expand the therapy to some HER2-low expression patients.
Application No. 17/058,838
Claims 84-87, 91-101, 103-107, 111-121, and 123 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 17 of copending Application No. 17/058,838 (hereinafter Appl. 838) in view of Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) and Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 838 teach a method of treating patient with a HER2-mutated non-small cell lung cancer with an ADC, wherein the ADC has the same drug component, the same linker and the same antibody of Trastuzumab deruxtecan (claim 1), as evidenced by Singh and Robblee.
As shown below,
Trastuzumab has a heavy chain of SEQ ID NO: 1 of Appl. 838:
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Trastuzumab has a light chain of SEQ ID NO: 2 of Appl. 838:
Query Match 100.0%; Score 1110; DB 1; 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
The claims of Appl. 838 do not teach the method also comprising generating response scores for the cancer patients as instantly claimed.
As set forth above in 103 rejection, Chukka teaches methods of generating single cell ADC scores and response scores based on antibody staining, image capture, image analysis, cancer cell identification and statistical analysis. Chukka teaches that the method are more objective and would help to identify patients for HER2-targeting therapies. Keam teaches that Trastuzumab deruxtecan is approved in the USA for cancer treatment and Trastuzumab deruxtecan can be used for HER2-positive metastatic breast cancers, HER2-low metastatic breast cancers, HER2-positive advanced gastric cancer, HER2-expressing advanced colorectal cancer and metastatic nonsquamous HER2-overexpressing or mutated non-small cell lung cancer. It is noted that Trastuzumab deruxtecan would read on the ADC of Appl. 838, as evidenced by Singh and Robblee.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 838, Chukka and Keam to treat cancer patients (e.g. a HER2-mutated non-small cell lung cancer) with Trastuzumab deruxtecan taught by Appl. 838 and Keam because Trastuzumab deruxtecan has been approved for breast cancer treatment and has shown therapeutic activity to various cancers, and to add a step of determining response score based on the method taught by Chukka. One of ordinary skilled in the art would have had a reasonable expectation that the modified method would lead to better therapeutic outcome, because the HER2-status is critical for a HER2-targeting therapy, the method taught by Chukka provides a more objective evaluation about the HER2 status. The motivation would have been to identify a suitable patient population for Trastuzumab deruxtecan and to expand the therapy to some HER2-low expression patients.
Application No. 18/367,446
Claims 84-87, 91-101, 103-107, 111-121, and 123 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/367,446 (hereinafter Appl. 446) in view of Chukka (Chukka et al., WO 2020/023213 A1, Publication Date: 01/30/2020, cited in IDS of 03/11/2023, of record) and Keam (Keam et al., Drugs (2020), 80: 501-508, Publication Date: 03/07/2020), as evidenced by Singh (Single et al., Journal of Controlled Release 340 (2021) 1-34, Publication Date: 10/19/2021) and Robblee (Robblee et al., US 2015/0104444 A1, Publication Date: 04/16/2015).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 446 teach a method of treating non-small cell lung cancer with an ADC, wherein the ADC has a drug component which is the same as the drug component and linker of Trastuzumab deruxtecan (claim 1).
The claims of Appl. 446 teach the antibody component of the ADC is an anti-HER2 antibody comprising a heavy chain consisting of the amino acid sequence of SEQ ID NO: 1 and a light chain consisting of the amino acid sequence of SEQ ID NO: 2 (claims 2 and 4).
As shown below,
Trastuzumab has a heavy chain of SEQ ID NO: 1 of Appl. 446:
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Trastuzumab has a light chain of SEQ ID NO: 2 of Appl. 446:
Query Match 100.0%; Score 1110; DB 1; 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
Taken together, the claims of Appl. 446 teach the ADC with the same drug component, same linker and the same antibody component as Trastuzumab deruxtecan, as evidenced by Singh and Robblee.
Taken together, the claims of Appl. 446 teach the ADC with the same drug component, the same linker and the same antibody component as Trastuzumab deruxtecan, as evidenced by Singh and Robblee.
The claims of Appl. 446 do not teach the method also comprising generating response scores for the cancer patients as instantly claimed.
As set forth above in 103 rejection, Chukka teaches methods of generating single cell ADC scores and response scores based on antibody staining, image capture, image analysis, cancer cell identification and statistical analysis. Chukka teaches that the method are more objective and would help to identify patients for HER2-targeting therapies. Keam teaches that Trastuzumab deruxtecan is approved in the USA for cancer treatment and Trastuzumab deruxtecan can be used for HER2-positive metastatic breast cancers, HER2-low metastatic breast cancers, HER2-positive advanced gastric cancer, HER2-expressing advanced colorectal cancer and metastatic nonsquamous HER2-overexpressing or mutated non-small cell lung cancer. It is noted that Trastuzumab deruxtecan would read on the ADC of Appl. 446, as evidenced by Singh and Robblee.
Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 446, Chukka and Keam to treat cancer patients (e.g. NSCLC patient) with Trastuzumab deruxtecan taught by Appl. 446 and Keam because Trastuzumab deruxtecan has been approved for breast cancer treatment and has shown therapeutic activity to various cancers, and to add a step of determining response score based on the method taught by Chukka. One of ordinary skilled in the art would have had a reasonable expectation that the modified method would lead to better therapeutic outcome, because the HER2-status is critical for a HER2-targeting therapy, the method taught by Chukka provides a more objective evaluation about the HER2 status. The motivation would have been to identify a suitable patient population for Trastuzumab deruxtecan and to expand the therapy to some HER2-low expression patients.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642