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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/15/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; 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.
For example, the “http” and “https” on page 36, para. 2 of the instant specification should be removed. Similar notation appears throughout the specification.
The specification is also objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Instant claim 13 recites a composition comprising an inhibitor of the genes listed in i). Such an inhibitor is not described in the instant specification. Correction is required. See also “Claim Interpretation” below.
Claim Interpretation
Regarding claim 1, the preamble of the claim states that the method is for “predicting the survival time of a subject suffering from uveal melanoma and/or metastatic uveal melanoma and treating the subject.” This is interpreted to give “life and meaning” to the claim, as it specifies the types of subjects that must be examined in the method. Similarly, claim 4 recites “treating uveal melanoma and/or metastatic uveal melanoma in a subject in need thereof” (emphasis added), which also imparts particular structure to the claim, as it limits the subjects that may be used. See MPEP 2111.02.
Regarding claim 12, the claimed kit includes instructions for a specific use (i.e. treating uveal melanoma and/or metastatic uveal melanoma). MPEP 2111.05 describes how printed matter, such as instructions, is evaluated in claims. If the printed matter does not have a functional relationship to the claimed product, than the printed matter itself has no patentable weight. MPEP 2111.05 I (B) specifically notes that when a kit has a printed set of instructions for using the items in the kit, the instructions are not functionally related to said items. Thus, in the instant claim set, claim 12 simply requires the presence of instructions, with no specific content requirement for said instructions.
Regarding claim 13, it is noted that this claim requires an immune checkpoint inhibitor and an inhibitor for the listed biomarkers. This appears to be contrary to the activator cited throughout the rest of the claim set, and such an inhibitor is not described in the instant specification. Because the instant claims were filed on the filing date of the application, they are considered a part of the original disclosure, and this is not new matter (see MPEP 608.04(b)), but Applicant is directed to this claim in the event a typographical error was made.
Claim Objections
Claim 1 is objected to because of the following informality: in the final line of step ii), “GSTA3 and H3F3A” should read “GSTA3 and/or H3F3A.” This is based on the use of “and/or” for the activator in dependent claims 8-11. Appropriate correction is required.
Claim 3 is objected to because of the following informality: in line 1, “sample is blood sample” should read “sample is a blood sample.” Appropriate correction is required.
Claim 7 is objected to because of the following informality: in the final line, “inhibitors of an immune checkpoints” should read “inhibitors of
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 1-11 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 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.
In particular, the specification does not reasonably provide enablement for utilizing the claimed biomarkers as signifiers for uveal melanoma or metastatic uveal melanoma, nor does it enable treating either of these diseases via the use of an activator for one or more of the claimed biomarkers.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). These factors include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. Each of these factors is discussed below.
Nature of the Invention
Claims 1-3 and 7-11 are drawn to a method for predicting survival time of a subject suffering from uveal melanoma and/or metastatic uveal melanoma and treating said subject with a therapeutically effective amount of a activator with a particular function.
Claims 4-6 are drawn to a method for treating uveal melanoma and/or metastatic uveal melanoma via the use of a therapeutically effective amount of an activator with a particular function.
The claimed methods are classified in the unpredictable arts of molecular biology and biochemistry.
Breadth of the Claims
Claim 1 is broad in scope in that any activator for any one of the recited biomarkers may be used. The claims are also broad in that the score used to determine if a treatment should be administered is not specifically identified. None of the dependent claims (2-3 and 7-11) limit the broad aspects of this claim.
Claim 4 is broad in scope in that any activator for any one of the recited biomarkers may be used. Claim 5 does not limit the broad aspect of this claim. Claim 6 recites particular types of molecules that may be used as the activator, limiting the scope slightly, but does not recite any particular activators.
Level of Skill in the Art
The ordinary artisan typically holds at least a master’s degree has several years of experience.
State of the Prior Art & Unpredictability
Concerning the claimed invention, what was (and is) unpredictable in the art is whether the claimed genes are known to be associated with uveal melanoma and/or metastatic uveal melanoma, and whether using a therapeutically effective amount of an activator for one or more of the listed genes would treat the disease. Therefore, it is not possible to know a priori that a particular score associated with the expression level of these genes would be indicative of uveal melanoma and/or metastatic uveal melanoma.
No prior art could be found linking all of the listed genes in conjunction with uveal melanoma and/or metastatic uveal melanoma.
Guidance in the Specification and Examples
The instant specification does generally discuss the claimed biomarkers throughout. See for example pages 1-6, 15, 18, and 21-22. Activators for these biomarkers are also generally discussed (e.g. pages 19-23). On page 20, para. 2, the activator is detailed as a small organic molecule, aptamer, antibody, peptide, or polypeptide in particular embodiments. However, no specific names of activators are provided.
In the working examples, the specifically claimed biomarkers are not recited. It is presumed that the TCGA and principal components analyses are related to the claimed biomarkers, as these analyses are mentioned earlier in the specification when discussing ways to calculate scores (page 3, para. 3). The top 10 genes on PC1 are correlated with survival, but the specific genes on this list are not stated (page 38, para. 4). The instant claims also contain 11 genes, so even if the 10 genes were all claimed, it is unclear which claimed gene would not be on PC1.The top 10 up and down regulated genes in the PC analysis appear to show correlation with the Youden index, but again, the specific genes involved are unclear (page 39, para. 5). Clustering analyses were also performed, but the genes involved in these clusters are not shown (page 40, paras. 2-3). Additional genes are mentioned in this example, though none are the genes claimed. Furthermore, no data appears to be presented as related to treating patients with a claimed activator. The drawings, which are associated with the results of the working examples, also do not specifically recite the claimed biomarkers or provide information about the claimed treatments.
Quantity of Experimentation
The ordinary artisan would have to conduct a very large quantity of highly unpredictable experimentation before being able to successfully practice the full scope of the claimed methods. Specifically, the ordinary artisan would have to determine that each of the claimed biomarkers is associated with uveal melanoma and/or metastatic uveal melanoma. Additionally, the ordinary artisan would have to determine which activators, if any, that are encompassed by the claims could be used to treat uveal melanoma and/or metastatic uveal melanoma. Based on the lack of teachings in the art, this would be an inventive and unpredictable undertaking, requiring extensive experimentation in which there is no guarantee of success. The large quantity of experimentation and its unpredictability constitute undue experimentation.
Conclusion
In view of the foregoing, it is clear that the specification fails to enable the full scope of the claimed methods, and claims 1-11 are rejected under 35 U.S.C. 112(a) for failing to comply with the enablement requirement.
Claim Rejections - 35 USC § 112(b)
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 1-3 and 7-12 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.
Claim 1 is rejected because in step ii), the method recites administering to “a subject identified as having a score…”. It is unclear if this subject is the same subject discussed in the preamble and step i) of the claim, or if this step is intending to recite a second subject. The claim will be interpreted as though the former explanation is correct. It is recommended to amend the claim to read, “administering to the subject a therapeutically effective amount of an activator of SPP1, EMCN, SYNPR, CTC- 340A15.2, HPGD, MTRNR2L8, PDE4DIP, COX6A2, AHCYL2, GSTA3 and H3F3A, wherein the subject is identified as having a score that is higher than a corresponding predetermined reference value” or similar language.
Claims 2-3 and 7-11 are rejected based on their dependence on rejected claim 1.
Claim 12 is also rejected because component i) of the kit is unclear. Specifically, component i) is “a reagent that specifically reacts with” a list of genes ending in “GSTA3, H3F3A mRNA or protein,” but the list is not written in the additive or alternative form (i.e. no “and”, “or”, or “and/or” is present). It is therefore unclear if only H3F3A may exist as an mRNA or protein in order for the reagent to react with it, or if all the listed genes may exist as mRNA or protein. It is also unclear if a single reagent must react with all of the listed genes, or if only one/at least one may be reacted with. It will be interpreted as though the reagent must react with at least one of the listed genes.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 12-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more. The claims recite natural products.
Claim 12 is directed to a kit containing a reagent for reacting with a particular mRNA or protein, as well as instructions for using the kit. Regarding the reagent, the instant specification notes that examples of such a reagent can be oligonucleotide probes, primers, peptides, and antibodies (pages 31-32 joining para.). Though it is not clear that oligonucleotides, peptides, and/or antibodies having the features recited in claim 12 exist in nature, the claimed reagents are, nevertheless, judicial exceptions because they are derived from naturally occurring molecules and are not required to possess any structural or functional differences relative to their naturally occurring counterparts. For example, the reagents of claim 12 are not required to include a detectable label. As well, the reagents do not have a function that differs from that of the naturally occurring counterparts since, like the naturally occurring counterparts, the claimed reagents bind to specific gene or protein targets. See also MPEP 2106.04(c) II. With regard to the claimed instructions, as the printed matter of the instructions has no functional relationship to the reagents in the kit, the presence of said instructions amounts insignificant extra-solution activity. See MPEP 2106.05(g). Thus, the claim as a whole is directed to products that are not markedly different from their naturally occurring counterparts.
Claim 13 is directed to a composition comprising an inhibitor for at least one gene and an immune checkpoint inhibitor, a BRAF inhibitor, and/or a MEK inhibitor. According to the instant specification, an “immune checkpoint inhibitor” refers to a molecule that inhibits a protein, and could be an antibody or native peptide (pages 7-8). The BRAF and MEK inhibitors that could be used are also not specified, and so may include only natural small molecules/antibodies/peptides. The gene inhibitor, as noted above in the “Specification” and “Claim Interpretation” sections, is not discussed in the instant specification, and so has a broadest reasonable interpretation that includes native antibodies and peptides as well. Though it is not clear that components having the features recited in claim 13 exist in nature, the claimed components are, nevertheless, judicial exceptions because they are derived from naturally occurring molecules and are not required to possess any structural or functional differences relative to their naturally occurring counterparts. For example, the components of claim 13 are not required to include a detectable label. As well, the components do not have a function that differs from that of the naturally occurring counterparts since, like the naturally occurring counterparts, the claimed components bind to specific gene and/or protein targets. See also MPEP 2106.04(c) II. Thus, the claim as a whole is directed to a group of products that are not markedly different from their naturally occurring counterparts.
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.
Claim 12 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weber (US 2009/0061436 A1).
It is noted that in claim 12, the reagent used may target a mRNA or protein for the recited biomarkers. For SPP1, the protein is known as Osteopontin (or OPN), as noted on page 4, para. 2 of the specification. Claim 12 does not state that variants or mutations of the mRNA/protein cannot be used, and so these are considered to be encompassed by the claim.
Weber teaches detection, treatment, and inhibition of the OPN variant OPN-c (Abstract). This variant of OPN contains a deletion in exon 4 (para. 5), as shown in Figure 1A. Weber teaches kits that contain reagents that target the OPN-c protein and/or the corresponding nucleic acid sequence. These kits can include antibodies, probes, and primers, as well as instructions for use (para. 62).
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.
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.
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 as of the effective filing date of the claimed invention(s) 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 as of the effective filing date of the later invention 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.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Weber (US 2009/0061436 A1) in view of Nakayama et al. (US 2019/0002588 A1).
Regarding claim 13, the claim does not specify whether DNA, RNA, or protein may react with the inhibitor. Thus, any of these options may be encompassed by the claim. Claim 13 does not state that variants or mutations of the DNA/RNA/protein cannot be used, and so these are considered to be encompassed by the claim.
Weber teaches detection, treatment, and inhibition of the OPN variant OPN-c (Abstract). This variant of OPN contains a deletion in exon 4 (para. 5), as shown in Figure 1A. Weber teaches use of a compound for inhibiting the activity of OPN-c, where the inhibitor may be a small molecule, peptide, or antibody. This compound can be administered to a cancer patient, and this compound can be used in conjunction with any known method of cancer treatment or prevention (para. 38). Weber also teaches that OPN-c is expressed in breast tumors/cancer (paras. 3 and 9-10 and Figures 1D and 2).
Nakayama teaches that effective treatments for breast cancer can include use of immune checkpoint inhibitors, either alone or in combination with other treatments (para. 4). Particularly, the reference notes that antibodies or binding fragments can be used with immune checkpoint inhibitors to treat breast cancer (paras. 221 and 300)
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Weber and Nakayama to arrive at the invention of instant claim 13. Weber teaches that other cancer treatments can be used in combination with the taught OPN-c inhibitors, and Nakayama teaches that one such cancer treatment is immune checkpoint inhibitors. Both references discuss breast cancer in particular, and so the ordinary artisan would be motivated to combine these treatments to provide more and/or better treatment options for these cancer patients, potentially improving outcomes. There would be a reasonable expectation of success as both types of treatments are already known, and the use of immune checkpoint inhibitors in combination with other therapies is also known, as evidenced by Weber and Nakayama.
Thus, claim 13 is prima facie obvious over Weber and Nakayama.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCESCA F GIAMMONA whose telephone number is (571)270-0595. The examiner can normally be reached M-Th, 7-5pm.
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/F.F.G./Examiner, Art Unit 1681
/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681