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 .
Response to Arguments
Claims 149-158 are examined on the merits. The rejections of 4 April 2025 overcome because intermittent administration of a tyrosine kinase inhibitor is not described in any of the references cited.
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.
Claim(s) 149-158 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to lack of written description.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, claims 149-158 are drawn to combination antineoplastic chemotherapy with a tyrosine kinase inhibitor and CAR-T immunotherapy.
(1) Level of skill and knowledge in the art:
ENDO (Biochemistry, 1996, 35, 5220-5228) describes different protein phosphatase 1 inhibitors (page 5224, table 1; page 5225, table 2).
CHOY (Journal of the American Chemical Society, 2017, 139, 17703-17706) describes that tautomycetin is a protein phosphatase 1 inhibitor (page 17703, figure 1).
HUANG (Proceedings of the National Academy of Sciences, 2000, 97:11, 5824-5829) describes that inhibitor 1, DARPP-32, and inhibitor 2 are heat stable protein phosphatase 1 subunits (page 5824, column 1, paragraph 1).
(2) Partial structure:
No partial structure for a protein phosphatase 1 inhibitor is described in the specification
(3) Physical and/or chemical properties and (4) Functional characteristics:
A protein phosphatase 1 inhibitor is a compound that inhibits protein phosphatase 1, which is a memory target in transgenic mice (Yang, The Journal of Neuroscience, 2015, 35(45), 15082-15087, specifically page 15087, first column, second paragraph).
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claim(s) 149-158 is/are broad and generic, with respect to PP1 inhibitors that could be present in the composition. The possible structural variations are limitless to any protein phosphatase 1 inhibitor. Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond those compounds specifically disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus. While having written description of PP-1 inhibitory compounds identified in the specification tables and/or examples, the specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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 149-158 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
What are the specific metes and bounds of PP1-inhibitor of the specified claims? Neither the claims nor the specification provide structural metes and bounds of the inhibitory compound? ENDO (Biochemistry, 1996, 35, 5220-5228) describes different protein phosphatase 1 inhibitors (page 5224, table 1; page 5225, table 2). CHOY (Journal of the American Chemical Society, 2017, 139, 17703-17706) describes that tautomycetin is a protein phosphatase 1 inhibitor (page 17703, figure 1). HUANG (Proceeding of the National Academy of Sciences, 2000, 97:11, 5824-5829) describes that inhibitor 1, DARPP-32, and inhibitor 2 are heat stable protein phosphatase 1 subunits (page 5824, column 1, paragraph 1). Are the PP1 inhibitors of Endo, Choy, and Huang intended to be present in a composition of claim 1?
Claims 149-158 recite the limitation “PP1-inhibitor” under the general heading tyrosine kinase inhibitor. There is insufficient antecedent basis for this limitation in the claim because a protein phosphatase 1 inhibitor is a different class of compounds relative to a tyrosine kinase inhibitor because the inhibited enzyme is different.
IS PP1inhibitor supposed to be compound PP1 itself, which is a tyrosine kinase inhibitor? SHIM (Oncology Letters, 2017, 13, 1463-1469) describes thar PP1 is tyrosine kinase inhibitor (page 465, table 1).
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(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.
Claims 149, 151, 152, and 154 are rejected under 35 U.S.C. 103(a) as being unpatentable over ROUSSELOT (Blood, 2016, 128(6), 774-782) and DAVILA (Clinical Advantages in Hematology & Oncology, 2016, 14(10), 802-808) in view of LYNN (WO 2018/183842, published 2018 October 4, priority to US provisional application 62/479930, 2017 March 31).
Determining the scope and contents of the prior art
Rousselot describes that intermittent dasatinib treats acute lymphocytic leukemia (page 780, column 1, paragraph 1).
Davila describes that CAR-T therapy can treat acute lymphocytic leukemia (page 804, column 1, paragraph 3 to page 805, column 2, paragraph 1).
Lynn describes that intermittent administration of a tyrosine kinase inhibitor results in 5-10 fold survival of CAR-T cells (page 30, line 14 to page 31, line 2; US provisional application 62/479930, specification page 16, lines 10-25)
Ascertaining the differences between the prior art and the claims at issue
The differences between the prior art and the claims at issue, a single reference does not describe all of the limitations of the examined claims.
Resolving the level of ordinary skill in the pertinent art
Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in combined chemotherapy of cancer with a tyrosine kinase inhibitor and CAR-T immunotherapy).
Considering objective evidence present in the application indicating obviousness or nonobviousness
In re Kerkhoven (205 USPQ 1069, 626 F2d 846) teaches:
It is prima facie obvious 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 which is to be used for the very same purpose.
When Kerkhoven is combined with Rousselot and Davila in view of Lynn, combination chemotherapy of intermittent dasatinib and CAR-T immunotherapy in acute lymphocytic leukemia (ALL) is possible. Both Rousselot and Davila describe the treatment of the acute lymphocytic leukemia. Lynn describes that intermittent dosing of CAR-T cells with a tyrosine kinase inhibitor results in increased survival of CAR-T cells, which leads to increased therapeutic ability of CAR-T. One of ordinary skill in the art would combine the known techniques described in Rousselot, Davila, and Lynn to treat acute lymphocytic leukemia with intermittent dasatinib and CAR-T immunotherapy.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Allowable Subject Matter
Claims 149-158 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NOBLE E JARRELL whose telephone number is (571)272-9077. The examiner can normally be reached 9:00 AM to 5:00 PM.
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/NOBLE E JARRELL/Primary Examiner, Art Unit 1699