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 .
Election/Restriction:
Applicant's election with traverse species of cancer: sarcoma, filed on 3/9/2026 is acknowledged. Applicant argues that all pending claims 1-22 are readable on the elected
species. Specifically, claims 1-3, 6-14, and 17-22 are generic to the elected species. Claims 4 and 15 recite a Markush group that includes the elected species of sarcoma. Claims 5 and 16 are directed specifically to the elected species of sarcoma. The various species of cancer recited in the claims-namely sarcoma, adenocarcinoma, and non-small lung cell cancer, all share a common property, which is that they are cancers that generate tumors that express the Axl protein, the invention, as defined by the generic claims, is directed to a method of treating any Axl-expressing tumor using a specific antibody-drug conjugate (mAbBA301-cleavable linker-MMAE) under a specific dosing regimen, and the particular type of Axl-expressing cancer is merely a variable in the application of this single inventive method. Applicant further argues that the shared property of Axl expression and the shared commonality of being treatable by the claimed method and composition provide the necessary technical relationship to form a single general inventive concept under PCT Rule 13.1. Therefore, Applicant submits that the Examiner withdraw the requirement and examine all claimed subject matter. Applicant’s arguments are persuasive and all species of cancer recited in claim 4 will be examined in the instant application.
Claims 1-22, are pending and under consideration by the Examiner.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on 3/9/2026, 7/15/2025, 10/3/2024, and 5/11/2023 are in compliance with the provisions of 37 CFR 1.97 and have been considered by the examiner.
Applicant is reminded of their duty to disclose to the Office all information known to the person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section”.
Claim Rejections - 35 USC § 112(a), first paragraph, scope of enablement
4. 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.
4a. Claims 1-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating an Axl expressing tumor comprising administering to a human subject in need of such treatment a pharmaceutical composition comprising mAbBA3 01-cleavable linker-MMAEn and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is administered at a dose of 1.8 mg/kg of the human subject weight on days 1 and 8 every 21 days by intravenous infusion; mAbBA301 is an antibody or antibody fragment having a heavy chain variable region comprising a hcCDR1 of SEQ ID NO. 14, a hcCDR2 of SEQ ID NO. 15 and a hcCDR3 of SEQ ID NO. 16; and a light chain variable region comprising a IcCDR1 of SEQ ID NO. 17, a IcCDR2 of SEQ ID NO. 18, and a IcCDR3 of SEQ ID NO. 19; and n is an integer between 1 and 4, inclusive, further comprising administering granulocyte colony stimulating factor (GCSF), does not reasonably provide enablement for a method of treating an Axl expressing tumor comprising administering to a human subject in need of such treatment a pharmaceutical composition comprising mAbBA3 01 -cleavable linker-MMAEn and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is administered at a dose of 1.8 mg/kg of the human subject weight on days 1 and 8 every 21 days by intravenous infusion; mAbBA301 is an antibody or antibody fragment having a heavy chain variable region comprising a hcCDR1 of SEQ ID NO. 14, a hcCDR2 of SEQ ID NO. 15 and a hcCDR3 of SEQ ID NO. 16; and a light chain variable region comprising a IcCDR1 of SEQ ID NO. 17, a IcCDR2 of SEQ ID NO. 18, and a IcCDR3 of SEQ ID NO. 19; and n is an integer between 1 and 4, inclusive, further comprising administering an analog of GCSF, as recited in claims 9 and 20. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Claim 1 recites “a method of treating an Axl expressing tumor comprising administering to a human subject in need of such treatment a pharmaceutical composition comprising mAbBA3 01 -cleavable linker-MMAEn and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is administered at a dose of 1.8 mg/kg of the human subject weight on days 1 and 8 every 21 days by intravenous infusion; mAbBA301 is an antibody or antibody fragment having a heavy chain variable region comprising a hcCDR1 of SEQ ID NO. 14, a hcCDR2 of SEQ ID NO. 15 and a hcCDR3 of SEQ ID NO. 16; and a light chain variable region comprising a IcCDR1 of SEQ ID NO. 17, a IcCDR2 of SEQ ID NO. 18, and a IcCDR3 of SEQ ID NO. 19; and n is an integer between 1 and 4, inclusive”, and claim 9 recites “…further comprising administering a granulocyte colony stimulating factor analog.”
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability, 5) existence of working samples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
With respect to the recitation of the limitation “GCSF analog” in claims 9 and 20, given the broadest reasonable interpretation, the term encompass hundreds, or even thousands of different “GCSF analogs”. The claims are broad in that they encompass treatment with any and all GCSF analogs while the specification only teaches administration of GCSF.
The state of the art with regards to GCSF analogs is discussed by US 2005/0123508 A1 which teaches that different GCSF analogs differ in potency and structure (See page 2, [0009]), and that some structural analogs of GCSF retain proper receptor activation for signal transduction, and have diminished endocytic internalization and lysosomal degradation (See page 3, [0026]-[0027]). Different GCSF analogs differ in binding to the cognate receptor, but the various GCSF analogs (natural and synthetic) have different cellular responses, and different GCSF receptor binding properties (See page 15, [0157]). Furthermore, the reference makes clear that the various GCSF analogs may not have the same properties, in this case, the therapeutic benefit of treating Axl expressing tumors as required by the instant claims.
The nature of the invention is a chemical case, wherein there is natural unpredictability in performance of certain species of GCSF other than the one specifically enumerated enabled in the specification. See MPEP 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the invention with the different GCSF analogs, with a reasonable expectation of success, because it would not be predictable from the disclosure, which particular species of GCSF analogue would work for treating Axl expressing tumors. See MPEP 2164.03.
The art demonstrates that GCSF analogs are different in structure and properties. It would be undue experimentation to determine which GCSF analogs could be administered in the instant method of treatment . Therefore, given the lack of guidance in the art, the lack of working examples commensurate in scope to the claimed invention and the unpredictability of GCSF analog therapy, the specification, as filed does, not provide enablement for the claimed method.
In the instant application, Applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ19 24 (CCPA 1970). Without such guidance, treatment with all “GCSF analogs” is unpredictable and the experimentation left those skilled in the art is unnecessarily and improperly, extensive and undue. See Amgen Inc. v Chugai Pharmaceutical Co. Ltd. 927 F 2d 1200,18 USPQ2d 1016 (Fed. Cir. 1991) at 18 USPQ2d 1026-1027 and Ex parte Forman, 230 U.S.P.Q. 546(Bd. Pat. App & int. 1986).
In view of all of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention, and thus, the claimed invention does not satisfy the requirements of 35 U.S.C. 112(a), first paragraph, scope of enablement.
Claim Rejections - 35 USC § 112(b)
5. 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.
5a. Claims 1-22 are 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 pre-AIA the applicant regards as the invention.
Claim 1, line 3, is vague and indefinite because it recites “mABBA301-cleavable linker MMAEn” and the meaning of the acronym “MMAEn” should be recited at its first use in an independent claim.
Claim 9 and 20 are rejected as vague and indefinite for reciting “granulocyte colony stimulating factor or an analog thereof”. The metes and bounds of the term “analog” are unclear because not all GCSF analogs are identical in structure or pharmacokinetics, and chemical modifications can lead to differences in duration of action, dosing frequency and sometimes immunogenicity. It is suggested that to obviate this rejection, the claim be amended to delete the recitation of “analog”.
Claims 2-8, 10-19, and 21-22 are rejected as vague and indefinite insofar as they depend on the above rejected claims for their limitations.
Claim rejections-35 U.S.C. 103
6. 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.
The following is a quotation of pre-AIA 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, 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
6a. Claims 1-5, 7-8, 10-16, 18-19, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0177417 Al (2019).
The reference discloses a method for treating cancer (a disease associated with the expression of Axl) comprising administering to a subject in need thereof with a pharmaceutical composition comprising an immunoconjugate and a pharmaceutically acceptable carrier, wherein the immunoconjugate comprises an anti-Axl antibody and at least one agent (MMAE) that are covalently bounded to a linker molecule (that corresponds to mAbBA301-cleavable linker-MMAEn), wherein the anti-Axl antibody comprises a heavy chain variable region
comprising three complementarity determining regions Hl, H2, and H3 sequence(Hl sequence is SEQ ID NO: l (WGATMN) (same as SEQ ID: 14), H2 sequence is SEQ ID NO: 2 (LIKPSNGGTSYNQKFKG) (same as SEQ ID: 15), and H3 sequence is SEQ ID NO: 3 (GHYESYEAMDYWG)(same as SEQ ID: 16)) and a light chain variable region comprising three complementarity determining regions Ll, L2, and L3 sequence (Ll sequence is SEQ ID NO: 4 (KASQDVVSAVA) (same as SEQ ID NO: 17), L2 sequence is SEQ ID NO: 5 (WQDTRHT) (same as SEQ ID NO: 18), and L3 sequence is SEQ ID NO: 6 (QEHFSPPLT) (same as SEQ ID NO: 19), a VH of SEQ ID NO:281 (same as instant SEQ ID NO:20) and a VL of SEQ ID NO:28 (same as instant SEQ ID NO:21 (see abstract; claims 1, 3, 7-8, 14-15, 17-19, 21; paragraphs [0354]-[0355], [0363], SEQ ID NO: 1-6; [0216], [0371], [0377], [0388], [0380]). The reference is silent with respect to administering the pharmaceutical composition dosage and period, and range of n.
However, one of skill in the art could easily derive the dosage from the teachings of reference in that, depending on the type and severity of the disease, about 1 ug/kg to
40 mg/kg of the claimed antibody can be an initial candidate dosage for administration to the patient, and such doses may be administered intermittently, every week or every three weeks, wherein the antibody is formulated for parenteral administration, such as intravenous injection(see paragraphs [0368], [0384], [0405]).
Therefore, to monitor the dosage and have the motivation and ability to optimize the best administration dosage and schedule of administration, to obtain the best and efficacious course of treatment would be obvious to the oncologist. Times of dosage, like dosage of administration, are “result effected variables”, that have an effect on the outcome of a method. Furthermore, such determination would have been well-within the skill set of one of ordinary skill in the art. In addition with respect to claims 7-8, and 18-19, since Axl is a marker for cancer on tumor membranes, the Axl antibody would target cells with high Axl , and therefore, the Axl expressing tumor would have a high tumor membrane P score.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215,219 (CCPA 1980). Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
The experimentation needed to arrive at the subject matter claimed was "nothing more than routine" application of a well-known problem-solving strategy, we must conclude it is not an invention. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed. Cir. 2007).
An improvement in the art would have been obvious if “it is likely the product not of innovation but of ordinary skill and common sense.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). Finding workable or optimal ranges is generally understood as within the capabilities of the ordinary artisan. See Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed. Cir. 2007) (discovery of an optimum value of a variable in a known process is usually obvious.). The idea that optimizing an ordinary variable does not by itself constitute a patentable advance was also stated in In re Geisler, 43 USPQ2d 1362: “…it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Only if the “results of optimizing a variable” are “unexpectedly good” can a patent be obtained for the claimed critical range. In re Antonie, 559 F.2d 618, 620, 195 USPQ 6, 8 (CCPA 1977); see also In re Dillon , 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed.Cir. 1990) (in banc).” Note MPEP §2144.05IIA on this issue
Likewise, optimization of a range or other variable within the claims flows from the “normal desire of scientists or artisans to improve upon what is already generally known.” In re Peterson, 65 USPQ2d 1379, 1382.
Therefore, the reference renders obvious claims 1-5, 7-8, 10-16, 18-19, and 21-22 in the absence of evidence to the contrary.
6b. Claims 1-8, 10-19, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0177417 Al (2019) in view of Mason et al (2017).
The teachings of US 2019/0177417 Al have been set forth above in paragraph 6a. The reference is silent with respect to administering a PD-1 blocking antibody in the claimed method of treatment.
Mason teaches a method using CFI-402257 and an anti-PD-1 antibody in mouse models of human colon cancer resulting in inhibition of tumor growth (See page 3131 2nd column), the anti-PD-1 antibody disrupts the PD-1/PD-L1 axis by preventing PD-1/PD-L1 binding by blocking the PD-1 on T-cells, thereby maintaining anti-tumor T-cell activity or blocking T-cell inhibitory activity, and causing tumor regression. Thus, the PD-1 blocking antibody of Mason, restored anti-tumor T-cell activity and blocked T-cell inhibition (See page 3129 2nd column bridging paragraph-page 3130 1st column).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art to modify the method of the US 2019/0177417 Al reference such that it includes administering a PD-1 antibody as taught by Mason, in combination with the Axl antibody of as taught by US 2019/0177417 Al, to obtain the known functions and advantages of both the Axl antibody and the PD-1 blocking antibody, as well as to increase the clinical efficacy of the claimed method since the combination could be synergistic. One would have been motivated to administer the PD-1 blocking antibody, because Mason teaches the advantage of administering the PD-1 blocking antibody for the treatment of cancer (see claims 4-5). To combine two compositions each of which is taught by the prior art to be useful for the same purpose in order to form a third composition that is to be used for very same purpose would have been obvious to one of ordinary skill in the art at the time the invention was made. The combination would have been obvious to the skilled artisan and the results achieved would have been expected (In re Kerkhoven, 205 USPQ 1069). Therefore, the combined teachings of US 2019-0177417 Al and Mason et al render obvious claims 1-8, 10-19, and 21-22.
6c. Claims 1-5, 7-16, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0177417 Al (2019) in view of US 2005/0123508 A1
The teachings of US 2019/0177417 Al have been set forth above in paragraph 6a. The reference is silent with respect administering GCSF with the Axl antibody in the claimed method of treatment.
US 2005/0123508 A1 teaches that G-CSF is useful in the treatment of cancer, by selectively stimulating and increasing neutrophil production in cancer patients to compensate for hematopoietic deficiency resulting from chemotherapy or radiation therapy (page 4, [0038]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art to modify the method of the US 2019/0177417 Al reference such that it includes administering GCSF as taught by US 2005/0123508 A1, in combination with the Axl antibody, to obtain the known functions and advantages of both the Axl antibody and GCSF and to increase the clinical efficacy of the claimed method since the combination could be synergistic. One would have been motivated to use GCSF, because US 2005/0123508 A1 teaches the advantage of administering GCSF for the treatment of cancer (see claims 10-11 and 14). To combine two compositions each of which is taught by the prior art to be useful for the same purpose in order to form a third composition that is to be used for very same purpose would have been obvious to one of ordinary skill in the art at the time the invention was made. The combination would have been obvious to the skilled artisan and the results achieved would have been expected (In re Kerkhoven, 205 USPQ 1069). Therefore, the combined teachings of the references renders obvious claims 1-5, 7-16, and 18-22.
Conclusion
Claims 1-22, are rejected.
No claim is allowed.
Advisory Information
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/PREMA M MERTZ/ Primary Examiner, Art Unit 1674
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