DETAILED ACTION
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 .
Status of Claims
The preliminary amendment filed 04/12/2024 is acknowledged. Claims 1-132 are cancelled. Claims 133-155 are new. Claims 133-155 are pending and under examination.
Claim Objections
Claims 133 and 137 are objected to because of the following informalities: the claim recites “a FOLR1-binding agent.” FOLR1 is not required to be defined as the art recognizes this acronym, but if it is to be defined, it should be in its first use and not in dependent claim 137. Appropriate correction is required.
Claim 136 is objected to because of the following informalities: The claim recites “about 3.0 to about 7.” Either both quantities should have a corresponding significant figure or neither. Appropriate correction is required.
Claim Rejections - 35 USC § 112b
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 151 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claim recites wherein the anti-FOLR1 antibody comprises the heavy and light chains encoded by the plasmids PTA-10772 and PTA-10774 that have been deposited with the American Type Culture Collection (ATCC). However, the examiner has been unable to locate an ATCC deposit corresponding to the disclosed accession numbers. Accordingly, neither the claims nor the specification provides an objective means by which one can determine the identity of the claimed antibody and the metes and bounds of the claim are unclear.
Therefore, claim 151 is rejected under 35 U.S.C. 112(b) as being indefinite.
Claim Rejections - 35 USC § 112a
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.
Claim 151 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claim requires an antibody comprising the heavy and light chain sequences identified by reference to a biological deposit. The examiner is unable to locate a deposit corresponding to the identified accession numbers at ATCC. Because the claimed antibody is defined by the deposited materials, and because they cannot be obtained, the disclosure does not enable one to make and use the claimed method without undue burden.
Accordingly, claim 151 is rejected under 35 U.S.C. 112(a) for lack of enablement.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 133-135 are rejected under 35 U.S.C. 102a1 as being anticipated by Ab et al. (WO2011106528A1).
Claims 133-135 are drawn to a method of reducing tumorigenicity of a tumor.
Of note, the VH and VL chains disclosed in instant SEQ ID NOs: 3 and 5 comprise the VH and VL CDRs disclosed in instant SEQ ID NOs: 6-9, 11, and 12. Thus, any embodiment disclosing SEQ ID NOs: 3 and 5 will necessarily comprise SEQ ID NOs: 6-9, 11, and 12.
Ab et al. teaches an immunoconjugate comprising an anti-FOLR antibody (instant claims 133, 134, 136, 138, 142, and 154) linked to an N(2')- deacetyl-N2-(4-mercapto-4-methyl-l-oxopentyl)-maytansine (DM4) (instant claims 138, 142) by either and N-succinimidyl 4-(2-pyridyldithio) butanoate (SPDB) linker [see par. 37] (instant claim 144) or an N-succinimidyl 4-(2-pyridyldithio)2-sulfobutanoate linker (sulfo-SPDB) linker [see par. 38] (instant claims 139 and 143). Ab et al. teaches that the anti-FOLR antibody comprises SEQ ID NOs: 4 and 11 [see par. 26], which correspond to instant SEQ ID NOs: 3 and 5 [see alignment below] (instant claims 135, 138, 140, 142, 150 and 154).
SEQ ID NO: 4 aligned to Instant SEQ ID NO: 3
Query Match 100.0%; Score 630; DB 1; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFY 60
Qy 61 NQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS 118
SEQ ID NO: 11 aligned to Instant SEQ ID NO: 5
Query Match 100.0%; Score 580; DB 1; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEA 60
Qy 61 GVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIKR 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIKR 112
Ab et al. teaches that the antibodies are muMov19 and its humanized version huMov19LCv1.6 [see Fig. 2]. Ab et al. teaches an embodiment in which the humanized antibody comprises 3.5-4 DM4 molecules [see par. 263] (instant claims 152 and 153) or 3.5-4 DM1 molecules (instant claim 154), the latter of which is linked by an N-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC) linker [see par. 264] (instant claim 155).
Ab et al. teaches a method of reducing tumorigenicity of a tumor comprising administering a therapeutically effective amount of a FOLR1-binding agent, which includes the above immunoconjugates, to a subject [see par. 229] (instant claim 133). The term “subject” is used interchangeably with the term “patient” and refers to a “human subject” [see par. 89] (instant claim 133). Ab et al. further teaches a method of treating cancer in a subject, which includes ovarian cancer and cancer of the peritoneum [see par. 86], comprising administering a therapeutically effective amount of a FOLR1-binding agent [see par. 223] (instant claims 136, 137, 142, 145, 147, and 154). Ab et al. teaches that an administering physician can easily determine optimum dosages and methodologies, including administration once every three weeks, once per month (four weeks), and at a dose between 0.1 mg to 20 mg per kg of body weight [see par. 237] (instant claims 141, 148, and 149).
Regarding claim 133, the limitation of “wherein the frequency of cancer stem cells in the tumor is reduced” is an expected outcome that does not introduce any active steps and is therefore interpreted as an inherent property of administering the composition.
Therefore, claims 133-135 are rejected under 35 U.S.C. 102a1.
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.
Claims 136-141, 154, and 155 are rejected under 35 U.S.C. 103 as being unpatentable over Ab et al. (WO2011106528A1).
Claims 136-141, 154, and 155 are drawn to a method for treating a patient having an FLOR1-expressing cancer.
The disclosure of Ab et al. is discussed above.
It would have been obvious and expected that a physician would optimize the administration dosage to the patient weight as Ab et al. teaches that the administering physician could easily do so based on known factors such as drug potency and patient weight. Reaching the claimed range of about 3.0-7.0 mg/kg, which encompasses one-fourth of the range disclosed by Ab et al., would have been a matter of routine optimization well within the skill of a person having ordinary skill in the art of administering therapeutics (instant claims 136 and 154). The limitation of “wherein the administration produces a Cmax of about 110-160 pg/mL” recites an expected outcome that does not introduce any active steps and is therefore interpreted as an inherent property of administering the claimed composition.
Therefore, claims 136-141, 154, and 155 are rejected under 35 U.S.C. 103.
Claims 142-145, 147-150, 152, and 153 are rejected under 35 U.S.C. 103 as being unpatentable over Ab et al., in view of Renouf et al., and in further view of Alffenaar et al. and Stanford et al.
Claims 142-145, 147-150, 152, and 153 are drawn to a method for treating a patient having an FLOR1-expressing cancer.
The disclosure of Ab et al. is discussed above.
Ab et al. does not teach or suggest administering the ADC according to adjusted ideal body weight (AIBW) or a specific formula for calculating AIBW.
Renouf et al. teaches that ocular toxicity was a recognized adverse effect of molecularly targeted anticancer agents because the antigens may also be expressed in ocular tissues [see abstract]. Renouf et al. discloses clinical observations in which ocular toxicity is associated with higher doses and longer treatment duration [see p. 3281, col. 2, par. 2] and teaches that such toxicities can be managed by dose interruption and/or dose reduction [see p. 3281, col. 1, par. 3].
Alffenaar et al. teaches that dosing of the antibiotic ethambutol according to total body weight rather than an appropriate alternative weight descriptor can result in overdosing in obese patients because of differences in drug distribution associated with altered body composition, and that ocular toxicity is one such outcome [see, p. 1, col. 1, par. 3]. Alffenaar et al. further teaches that differences in body composition can affect pharmacokinetic parameters and that weight-based dose corrections can reduce the total administered dose [see p. 1, col. 1, par. 3]. Alffenaar et al. identifies lean body weight, ideal body weight, and adjusted ideal body weight as alternative size descriptors and provides a comparison demonstrating that adjusted weight results in lower total doses than total body weight [see p. 1, col. 1, par. 3]. Alffenaar et al. therefore teaches that selection of an appropriate weight descriptor is important when administering a weight-based drug to an obese patient.
Stanford et al. teaches the use of adjusted body weight as a weight descriptor for weight-based dosing and recites an established ideal body weight calculation based on the patient’s sex and height [see top of document]. The claimed formula uses a 0.4 correction factor and only differs from the claimed formula in that it uses inches instead of centimeters as the unit of measurement for IBW. When expressed as centimeters, the IBW equation disclosed by Stanford et al. is 0.9055H-88 for males and 0.9055-93 for women, which, considering rounding, is nearly identical to the claimed equation.
It would have been obvious to a person having ordinary skill in the art to administer the composition disclosed by Ab et al. using an appropriate weight descriptor such as through the AIBW method as taught by Stanford et al. because Renouf et al. teaches that ocular toxicity is a recognized adverse effect associated with targeted anti-cancer therapies and that dose reduction is an established approach for managing such toxicity, Alfenaar et al. teaches that total body weight dosing can result in excessive dosing and increased drug exposure in obese patients and that alternative size descriptors, such as AIBW, were proposed for correcting such dosing, and Stanford et al. provides an established clinical methodology for implementing such correction in the administration of therapeutics. The implementation of this alternative method constitutes applying a known dosing methodology to a known weight-based therapeutic regimen to address a known problem, with the expected result of reducing the overall dose and thereby reducing ocular toxicity. Arriving at the claimed formula in centimeters would have been a routine design choice and arriving at the claimed dose of 6 mg/kg would have been a matter of routine optimization well within the skill of a person having ordinary skill in the art of administering therapeutics.
Accordingly, claims 142-145, 147-150, 152, and 153 are rejected under 35 U.S.C. 103.
Claims 142, 145, and 146 are rejected under 35 U.S.C. 103 as being unpatentable over Ab et al., in view of Renouf et al., Alffenaar et al., Stanford et al., and in further view of Prat et al.
Claims 142, 145, and 146 are drawn to a method for treating a patient having an FLOR1-expressing cancer.
The disclosure of Ab et al., Renouf et al., Alffenaar et al., and Stanford et al. are discussed above.
The combination of these references does not teach or suggest that the cancer is a specific type of ovarian cancer.
Prat et al. discloses that epithelial ovarian cancers are the most common type of ovarian cancer and accounts for over 90% of cases [see p. 1, col. 1, par. 3].
A person having ordinary skill in the art would have understood Ab et al.’s disclosure of a treatment for “ovarian cancer” as a treatment for epithelial ovarian cancer as the art teaches that the vast majority of ovarian cancers are of epithelial origin. In the alternative, it would have been obvious to apply the composition of Ab et al. for the treatment of epithelial ovarian cancer for the same reason.
Therefore, claims 142, 145, and 146 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tirone D Johnson whose telephone number is (571)272-1256. The examiner can normally be reached M-F, 9-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIRONE D. JOHNSON/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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