DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 3-6, 10-11, 20-21, 24-38 are pending.
Election/Restrictions
Applicants' election without traverse of Group I, claims 3-5 and 31-38, in the reply filed on 3/23/26 is acknowledged. As set forth in the restriction requirement, claims 6, 10-11, 20-21 and 26-30 are linking claims that will be examined together with Group I.
Claims 24 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elections (1) colorectal cancer as the species of cancer and (2) pembrolizumab as the species of second therapeutic in the reply are also acknowledged. The elected species read on each claim in the elected group.
Claims 3-6, 10-11, 20-21 and 26-38 are under consideration.
Specification
The disclosure is objected to because of the following informalities:
---The title of the invention is not descriptive because (1) in part it is directed to an antibody binding CTLA-4, which is a product, but the pending claims are limited to methods; and (2) in part it is directed generally to “use thereof” of the antibody, which encompasses any use, but the claims are limited to methods of using the antibody for treatment of cancer. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Methods for Treating Cancer with an Anti-CTLA-4 Antibody”.
---The disclosure is objected to because it contains embedded hyperlinks (browser-executable code) on page 41, line 30, and page 42, line 23. Applicants are required to remove the embedded hyperlinks; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01 (VII).
Appropriate correction is required.
Drawings
Corrected drawings in compliance with 37 CFR 1.121(d) are required because:
---Figures 1, 3, 4 and 7 each include text and symbols that are illegible due to a small size (e.g., font) and blurriness. Per MPEP 608.01.I, “papers that are to become a part of the permanent [USPTO] records in the file of a patent application or a reexamination proceeding, in a form that is clear and reproducible. If the papers are not of the required quality, substitute papers of suitable quality will be required”. See also 37 CFR 1.52(a). As such, Applicants must correct the specification such that the table on page 64 is legible.
Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). Applicants are advised to employ the services of a competent patent draftsperson outside the Office, as the USPTO no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Objections
Claims 30 and 36 are objected to for the following informalities:
In claim 30, line 3, the second clause of the claim is missing a “wherein” at the beginning, i.e., “wherein the anti-CTLA-4 single heavy-chain antibody…” Compare with the first clause starting on line 1, and the third clause starting on line 5.
Claim 36 is objected to for the same reason as claim 30.
Appropriate correction is required.
Note on Prior Art Rejection(s)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 6, 11, 20-21, 26-27 and 29-30 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gan et al, U.S. Patent Application 20190202914, published 7/4/19, filed 12/19/18 and claiming priority to 12/20/17 (cited on the 2/15/24 IDS). The earliest date to which the instant application claims priority is 4/20/21.
Claim 6 encompasses a method for treating cancer comprising the step of administering to a subject in need thereof, an anti-CTLA-4 sing heavy-chain antibody that has CDR1-3 sequences of SEQ ID NO: 1, 9 and 17. It is noted that claim 6 optionally recites further administration of a second therapeutic agent, but because this is optional, the claim encompasses embodiments without administration of such.
Gan teaches single heavy chain antibodies that bind CTLA-4 (also termed CD152), including one termed CL5-dPTM’ that encompasses CDR1-3 of SEQ ID NO: 112, 113, and 114 (See Table 4), which are 100% identical to instant CDR1-3 of SEQ ID NO: 1, 9 and 17. Gan further teaches a method for treating cancer using the anti-CTLA-4 antibodies of the invention (e.g., at ¶ 105-106). As such, the teachings of Gan anticipate claim 6.
Claims 11, 29 and 30 encompass a method of claim 6 wherein the dose of the antibody is further limited, either to a range of 0.2 mg/kg to 1 mg/kg body weight (claim 11), to a range of 0.3 to 0.6 mg/kg (claim 29) or to 0.3 mg/kg once every week. Gan in ¶ 115 further teaches dosages for administration of the anti-CTLA-4 antibodies of the invention, and the exemplary dosages include “0.3 mg/kg body weight”, which is within the ranges recited in claims 11 and 29. Gan further teaches “administration once per week” as an “exemplary treatment regimen” (¶ 115). As such, the teachings of Gan also anticipate claims 11, 29 and 30.
Claim 20 encompasses a method of claim 6 wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 25. Gan further teaches that the CL5-dPTM’ antibody has a heavy chain variable region of SEQ ID NO: 111, which is identical to instant SEQ ID NO: 25. As such, the teachings of Gan also anticipate claim 20.
Claim 21 encompasses a method of claim 6 wherein the antibody comprises a heavy chain sequence comprising SEQ ID NO: 33. Gan further teaches a CL5-eA-dPTM’ antibody has a heavy chain variable region of SEQ ID NO: 182 (Table 4), which is identical to instant SEQ ID NO: 33. As such, the teachings of Gan also anticipate claim 21.
Claim 26 encompasses a method of claim 6 wherein the cancer is melanoma or colorectal cancer. Gan further teaches that the cancer to be treated can be melanoma or colorectal cancer (¶ 106). As such, the teachings of Gan also anticipate claim 26.
Claim 27 limits the method of parent claim 6 to one wherein the method removes a regulatory T cell (Treg). This wherein clause has been fully considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Specifically, claim 27, the further wherein clause simply express the intended result (removal of Tregs) of a process step positively recited (administered the anti-CTLA4 antibody). As such, the teachings of Gan that anticipate parent claim 6 also meet the limitations of dependent claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 10 and 28 are rejected under 35 U.S.C. 103(a) as being unpatentable over Gan et al, U.S. Patent Application 20190202914, published 7/4/19, filed 12/19/18 and claiming priority to 12/20/17 (cited on the 2/15/24 IDS), as applied to claim 6 above, and further in view of Yervoy Label, dated 12/2013, no author indicated, pages 1-24; available at www.accessdata.fda.gov/drugsatfda_docs/label/2013/125377s055lbl.pdf, and further in view of Arfan et al, 2020 (September), International Journal of Engineering & Technology, 9(9): 967-971.
Claims 10 and 28 each depend from claim 6, and further limit route, concentration, formulation and/or timing of the administered antibody. Each claim requires “intravenous drip infusion”, and claim 10 further requires a concentration of 0.1 mg/mL to 10.0 mg/mL in 0.9% sodium chloride or 5% glucose solution; and claim 28 further requires that the i.v. drip infusion is given for no more than 4 hours.
The teachings of Gan that anticipate parent claim 6 are set forth above. Gan further teaches that the antibodies of the invention can be given intravenous infusion (¶ 97), but does not specify that it is drip infusion.
The Label for Yervoy teaches that it is a “(CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma”, which is administered by “intravenous infusion” (page 1) with a time of “90 minutes” (page 1). The Label further teaches that for administration the antibody should be diluted with 0.9% sodium chloride or 5% dextrose (which is another name for glucose) at “a final concentration ranging from 1 mg/mL to 2 mg/mL” (page 4). The Label for Yervoy does not specify that the intravenous infusion is intravenous drip infusion.
Arfan teaches that “intravenous (IV) drip mode is one of the most used modes for drug delivery” (see Abstract). Arfan teaches that “DripAssist Infusion Rate Monitor device is known to deliver precise and fast IV infusion. It can manage and monitor IV drip without pump, easily and can use gravity infusion. There is no need for the following parameters like maintenance, calibration or asset tracking. It is a small device and has appreciable versatility and portability. The drip count is accurate and reliable for any fluid or medication” (page 969).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating cancer in a subject in need thereof by administering an anti-CTLA-4 antibody comprising CDR1-3 of SEQ ID NO: 1, 9 and 17 that is taught by Gan that meets the limitations of parent claim 6, and further modify it to make the administration by intravenous infusion for 90 minutes at a concentration of 1-2 mg/mL and in 9% NaCl or 5% glucose as taught by the Yervoy Label, and further to modify the intravenous infusion to be intravenous drip infusion as taught by Arfan. The person of ordinary skill in the art would have been motivated to make such changes because Gan teaches use of intravenous infusion to administer the anti-CTLA-4 antibody, but does not specify the timing, concentration or diluent for administration, and the Yervoy Label provides such information, and the person of ordinary skill in the art would have further been motivated to use i.v. drip infusion in order to employ the advantages taught by Arfan. The person of ordinary skill in the art would have had a reasonable expectation of success in practicing the modified method because the antibody of Gan and that taught by the Yervoy Label each target the same molecule (CTLA-4) for the same indication (cancer treatment), and further because Arfan teaches use of i.v. drip infusion generally for any type of drug. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claims 3-5, 31 and 34-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Gan et al, U.S. Patent Application 20190202914, published 7/4/19, filed 12/19/18 and claiming priority to 12/20/17 (cited on the 2/15/24 IDS), as applied to claim 6 above, and further in view of Lala et al, WO 2019/160755, published 22 August 2019.
Claim 3 is an independent claim encompassing a method for treating a refractory cancer in a subject comprising administering a subject in need thereof an anti-CTLA-4 antibody having CDR1-3 of SEQ ID NO: 1, 9 and 17. Claim 4 further limits the refractory cancer, and encompasses a refractory cancer that is not responsive to a PD-1 axis signalling pathway inhibitor. The teachings of Gan that anticipate independent claim 6 are set forth above. These teachings meets all of limitations of claim 3, except that Gan does not teach that the cancer is refractory.
Lala teaches treatment of subjects with “advanced melanoma that is refractory to anti-PD1/L1” with “an anti-CTLA4 antibody” (page 59, lines 36-38).
It would have been to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treating cancer in a subject in need thereof by administering an anti-CTLA-4 antibody comprising CDR1-3 of SEQ ID NO: 1, 9 and 17 taught by Gan that meets the limitations of claim 6, and further modify it to apply the treatment to a patient having melanoma refractory to anti-PD1 or PD-L1 as taught by Lala. The person of ordinary skill in the art would have been motivated to make such changes in order to direct the treatment of Gan to a melanoma patient subpopulation having refractory melanoma, and to provide a treatment to a patient that is no longer responding to anti-PD-1 or anti-PD-L1 therapy. The person of ordinary skill in the art would have had a reasonable expectation of success in practicing the modified method because the antibody of Gan and that taught by Lala target the same molecule (CTLA-4) for the same indication (cancer treatment). This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007). The modified method obvious over the teachings of Gan in view of Lala meets the limitations of claims 3 and 4.
Claims 5, 31, and 34-38 each further limit the method claim 3 in the same manner that claims 26-27, 11, 29-30, 20 and 21, respectively, further limit the method of claim 6. The teachings of Gan that meet the further limitations of each of these claims is set forth above. As such, it would have further been obvious to include any of these embodiments when practicing the modified method obvious over the teachings of Gan in view of Lala that meets the limitations of claims 3 and 4.
Claims 32 and 33 are rejected under 35 U.S.C. 103(a) as being unpatentable over Gan et al, U.S. Patent Application 20190202914, published 7/4/19, filed 12/19/18 and claiming priority to 12/20/17 (cited on the 2/15/24 IDS) and further in view of Lala et al, WO 2019/160755, published 22 August 2019, as applied to claim 3 above, and further in view of Yervoy Label, dated 12/2013, no author indicated, pages 1-24; available at www.accessdata.fda.gov/drugsatfda_docs/label/2013/125377s055lbl.pdf, and further in view of Arfan et al, 2020 (September), International Journal of Engineering & Technology, 9(9): 967-971.
Claims 32 and 33 each further limit the method claim 3 in the same manner that claims 10 and 28, respectively, further limit the method of claim 6. As such, it would have further been obvious to take the modified method obvious over the teachings of Gan in view of Lala that meets the limitations of claims 3 and 4, and further modify this method to make the administration by intravenous infusion for 90 minutes at a concentration of 1-2 mg/mL and in 9% NaCl or 5% glucose as taught by the Yervoy Label, and further to modify the intravenous infusion to be intravenous drip infusion as taught by Arfan. The person of ordinary skill in the art would have been motivated to make such changes, and would have had a reasonable expectation of success in practicing the modified method, for the same reasons set forth above with respect to the obviousness of parent claim 3 in view of the teachings of Gan in view of the Yervoy Label and Arfan. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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