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 .
Claim Rejections 35 USC 112(A)
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 1-18, 22 and 23 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. For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
actual reduction to practice/(b) disclosure of drawing or structural chemical formulas:
Applicants have not reduced any MrgprX4 antagonists to practice in the examples of the specification. The examples are drawn to showing the role of MrgprX4 in melanoma, and that cell proliferation is reduced in MrgprX4 KO mice, but they do not administer or produce and test any MrgprX4 antagonists.
sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
The claimed structure of MrgprX4 antagonists, are drawn to an extremely broad structure, with no common core or identifying characteristics. The claims are drawn to them being antibodies, fragments of antibodies, binding proteins, polypeptides and small molecules. As of 2019, no MrgprX4 antagonists had been developed (Yu et al. eLife 2019; 8: e48431; p. 18, para. 2). Additionally, claim 10 requires the antagonist to function as treating melanoma in meninges, which requires the antagonist to function as binding in the protective layers of the spinal cord and/or brain. As of now, applicants have only submitted MrgprX4 antagonists small molecules identified in WO2018/232316 and US2021/0032213, which does not support the structure-function relationship of such a broad genus of antagonists with little to no guidance as to what structural portions are required for the claimed antagonist function. Furthermore, because the claims are drawn to methods as well, and there is no support in the specification to show that there are antibodies, fragments proteins and polypeptides that can serve this function.
(d) Representative number of examples
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.").
The specification only discloses 81 small molecules that are known to be MrgprX4 inhibitors, with no guidance as to what minimal structure is required to bind to MrgprX4 or any additional examples beyond small molecules from the prior art. Given this lack of description in the specification, the application fails to describe the claimed invention in such a full, clear, and concise and exact terms that a skilled artisan would recognize that applicants were in possession of the genus of claimed invention.
Claim Rejections 35 USC 102(A)
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.
Claim(s) 18, 22 and 23 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Dong et al. (US2020/0173985A1).
Dong further teaches administering an effective amount of a pharmaceutical MrgprX4 antagonist composition to the subject to treat a G protein coupled receptor-mediated condition, which includes melanoma [0019; 0055; 0059]. This reference also teaches written instructions are for treating malignant transformations (cancer) and skin disorders [0020; claim 38]. Dong also teaches that the MrgprX4 antagonist may be an antibody or fragment thereof, a binding protein, a polypeptide, a small molecule or combinations thereof [0016].
This meets the limitations of claims 18 by teaching pharmaceutical formulations of MrgprX4 antagonists in an effective amount for administration. The intended use of this composition is inherent to the claimed composition itself, and has no bearing on the patentability of the composition. The MPEP 2112 states:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP § 2112.01 with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103.”
As such, the claimed pharmaceutical compositions are not distinguished by a limitation that merely designates intended use.
Claim 22 is met because Dong teaches that the MrgprX4 antagonist may be an antibody or fragment thereof, a binding protein, a polypeptide, a small molecule or combinations thereof [0016].
As to claim 22 having the limitation “written instructions for treating melanoma,”, MPEP 2112 also states: Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004) (Claim at issue was a kit requiring instructions and a buffer agent. The Federal Circuit held that the claim was anticipated by a prior art reference that taught a kit that included instructions and a buffer agent, even though the content of the instructions differed, explaining "[i]f we were to adopt [applicant’s] position, anyone could continue patenting a product indefinitely provided that they add a new instruction sheet to the product."). See also In re Gulack, 703 F.2d 1381, 1385-86, 217 USPQ 401, 404 (Fed. Cir. 1983) ( "Where the printed matter is not functionally related to the substrate, the printed matter will not distinguish the invention from the prior art in terms of patentability….[T]he critical question is whether there exists any new and unobvious functional relationship between the printed matter and the substrate." ); In re Miller, 418 F.2d 1392, 1396 (CCPA 1969) (finding a new and nonobvious relationship between a measuring cup and writing showing how to "half" a recipe); In re Seid, 161 F.2d 229, 73 USPQ 431 (CCPA 1947) (matters relating to ornamentation only which have no mechanical function cannot be relied upon to patentably distinguish the claimed invention from the prior art); In re Xiao, 462 Fed. App'x 947, 950-51 (Fed. Cir. 2011) (non-precedential) (affirming an obviousness rejection of claims directed to a tumbler lock that used letters instead of numbers and had a wild-card label instead of one of the letters); In re Bryan, 323 Fed. App'x 898, 901 (Fed. Cir. 2009) (non-precedential) (printed matter on game cards bears no new and nonobvious functional relationship to game board).
As such, the claimed instructions for treatment do not distinguish the composition from that which was known in the art, and claims 18, 22 and 23 are anticipated.
Claim Rejections 35 USC 103
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.
Claim(s) 1-9, 11-18, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Dong, as applied to claims 18, 22 and 23 above, in view of Samuels et al. (US2013/0190374).
The difference between the prior art and the instant claims is that Dong does not specifically reduce to practice treating, diagnosing or screening for drugs that treat melanoma as the G Protein coupled skin disorder.
However, Dong teaches cells and methods for detecting compounds that affect G protein coupled receptor mediated conditions (Abstract). This reference teaches using MrgprX4-expressing cell lines in a method of high through-put screening for drug candidates and blocking MrgprX4 to treat adverse drug reactions, malignant transformations and skin diseases [0007]. Specifically, Dong teaches a method for screening for drug agents that modulate one or more MrgprX4 G protein coupled receptor-mediated conditions or disorders comprising: contacting one or more cells expressing an MrgprX4 or MrgprX3 G protein coupled receptor with a candidate drug agent, detecting a response of the one or more cells and selecting the candidate drug agent for evaluation to modulate the G protein coupled receptor-mediated condition or disorder [Claim 1].
Samuels teaches a method for diagnosing melanoma in a subject by determining the presence of a mutation on the G-protein coupled receptors in a tissue sample and using this as an indicator of whether the subject has melanoma [Abstract]. This reference teaches using G-protein coupled receptor (GPCR)-directed mutational analysis of tumor DNA obtained from melanoma tissue samples, specifically metabotropic 3 (GRM3) mutations, as this has been identified as the most highly mutated GPCR gene in this screen [Abstract]. This reference teaches methods of diagnosing a subject as having melanoma, or susceptible to developing melanoma, by detecting the presence of at least one mutation in GRM3 and methods of treating a subject by subsequently administering an appropriate therapy [Abstract].
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the MrgprX4 antagonists of Dong and used them to treat and detect melanoma because Dong and Samuels both teach melanoma as one type G-protein coupled disorder. One would be motivated to do so because Samuels further emphasizes that melanoma can be detected by looking to the levels of G-protein coupled receptor expression and activation, and Dong teaches that MrgprX4 antagonists reduce activation. As such, there is a reasonable expectation of success that the MrpgrX4 antagonists of Dong can effectively treat, diagnose and screen drugs for the G-protein coupled disorder, melanoma.
This meets the limitations of claim 1 because Dong teaches treating G-protein coupled disorders with MrpgrX4 and melanoma is a G protein coupled disorder. Claims 2-5 are met because Dong teaches antibodies, fragments, small molecules, binding proteins and polypeptides as MrgprX4 antagonists. Claims 7-9 are rendered obvious because Dong teaches identifying a G protein mediated disorder by administering an MrgprX4 antagonist to a subject, and Samuels provides further evidence that melanoma of the skin and eye are G protein mediated disorders. Claims 11 and 12 are met because Dong teaches identifying the presence, absence, or amount of MrgprX3 or MrgprX4 activation of a signal transduction and Samuels teaches identifying melanoma by the presence of a G-protein coupled receptor mutations in a sample, thus rendering it obvious to diagnose the presence of melanoma with the G protein activator, MrgprX4. Claims 13-14 are rendered obvious because Dong teaches screening for drug agents that modulate MrgprX4. Claim 15 is met because Dong teaches using skin cell samples [0010]. Claim 16 is rendered obvious because Samuels teaches that melanoma originates in melanocytes, which would be obvious to choose for a cell sample. Claim 17 is met because Dong teaches that detecting intracellular calcium is an alternative marker for MrgprX4 activation.
As such, claims 1-9 and 11-17 are rendered obvious.
Conclusion
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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