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 .
Status of the Claims
No restriction requirement is being imposed in this case. Claim 1 is pending and under examination.
Effective Filing Date
Applicant’s claim for the domestic benefit of prior-filed applications under 35 U.S.C. 119(e), 120 and 365(c) is acknowledged. No foreign priority claims are made. Based on an inspection of the prior applications and patent, the examiner has concluded that the subject matter defined in instant claim 1 is supported by the disclosure in application serial no. 17/929,510 (now abandoned), application serial no. 16/090,066 (now US Patent 11,474,105), PCT/US2017/025339 and at least provisional application serial no. 62/316,163. Thus, the priority date of instant claim 1 is deemed to be 03/31/2016.
Drawings
The drawings are objected to because there has been no granted petition to include color drawings in this application. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. 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). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Figures 2, 4 and 5 contain color photographs and/or drawings. Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
More specifically, 37 C.F.R. 1.84(a)(2) states:
. . . On rare occasions, color drawings may be necessary as the only practical medium by which to disclose the subject matter sought to be patented in a utility patent application. . . . The Office will accept color drawings in utility patent applications only after granting a petition filed under this paragraph explaining why the color drawings are necessary. Any such petition must include the following:
(i) The fee set forth in § 1.17(h);
(ii) One (1) set of color drawings if submitted via the Office electronic filing system, or three (3) sets of color drawings if not submitted via the Office electronic filing system; and
(iii) An amendment to the specification to insert (unless the specification contains or has been previously amended to contain) the following language as the first paragraph of the brief description of the drawings:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
(Emphases added.) MPEP 608.02, part VIII, states:
Color drawings and color photographs are not accepted in utility applications filed under 35 U.S.C. 111 unless a petition filed under 37 CFR 1.84(a)(2) or (b)(2) is granted. Color drawings and color photographs are not permitted in international applications (see PCT Rule 11.13 ).
Unless a petition is filed and granted, color drawings or color photographs will not be accepted in a utility patent application filed under 35 U.S.C. 111. The examiner must object to the color drawings or color photographs as being improper and require applicant either to cancel the drawings or to provide substitute black and white drawings.
Specification
The title of the invention is not descriptive. 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 SIRT1 AND BCL6 EXPRESSION AS A MARKER FOR INFERTILITY.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim recites diagnosing and treating infertility in a subject comprising detecting SIRT1 and BCL6 gene and/or protein levels in a subject and comparing said levels to a control, wherein the subject is diagnosed as having endometriosis when the SIRT1 and BCL6 levels are higher than controls, which is the statutory category of a process (see Step 1 of the Revised Guidelines). The diagnostic step (f) recites “diagnosing the subject as having infertility when the subject has a level of expression”. The term “when” is interpreted as “if”, thus, step (g), which recites “administering to the subject” is interpreted as conditional upon the diagnostic step (f). In other words, the administering step is performed only if the subject is diagnosed as having infertility.
The first prong of the two-prong inquiry for determining whether a claim recites an abstract idea is to consider whether it is directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exceptions—see Step 2A). The mental process recited in claim 1 is diagnosis based upon a comparison of the SIRT1 and BCL6 levels to controls and determining that the SIRT1 and BCL6 levels are higher in the subjects than the controls. The mental step of comparing biomarker levels is similar to comparing information regarding a sample or test subject to a control or target data (see Univ. of Utah Research Found, v. Ambry Genetics Corp., 113 USPQ2d 1241 (Fed. Cir. 2014), or diagnosing an abnormal condition by performing clinical tests and thinking about the results (see In re Grams, 12 USPQ2d 1824 (Fed. Cir. 1989). See the first prong of Step 2A of the Revised Guidelines. In summary, the judicial exception is the diagnostic (comparing) step recited in claim 1, which entails making a determination of infertility based upon a finding of higher levels of SIRT1 and BCL6 levels in subjects vs. controls.
The second prong of Step 2A is to consider whether the claim recites additional elements that integrate the judicial exception into a practical application. Claim 1 recites treatment with an effective amount of a BCL6 or SIRT1 inhibitor or a treatment that blocks BCL6 or SIRT1 activity, singly or in combination. Thus claim 1 encompasses treatment with an unnamed “inhibitor” of the overexpressed genes/proteins. In order to integrate the judicial exception into a practical application, the treatment must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exception. The recitation of treatment with unnamed inhibitors to the genes and/or proteins that happen to be overexpressed amounts to an instruction to apply the exception in a general way; similar to a recitation of “administering a suitable medication to the subject”.
The final step in the consideration of whether a claim is patent eligible is to consider whether there are additional elements in the claims sufficient to amount to significantly more than the judicial exception (see Step 2B of the Revised Guidelines). The issue raised regarding the lack of particularity of treating a subject with a generic treatment, namely a treatment that inhibits the overexpressed genes/proteins was discussed in the preceding paragraph and is applicable herein. The generic nature of the inhibitors amounts to an “apply it” type limitation of the judicial exception in the treatment step. The claims also recite detection of the level of a SIRT1 or BCL6 gene or protein. Measurement of SIRT1 and BCL6 was well-understood, routine and conventional in the prior art. For instance, Vaquero et al. (Molecular Cell, 2004; 16: 93-105—on IDS filed 08/12/2024) teach the detection of SIRT1 protein in cell lines using an SIRT1 monoclonal antibody (see for instance, p. 94, Figures 1A-1C). In addition, Chamdin et al. (Translational Oncology, 2009; 2: 128-137—on IDS filed 08/12/2024) teach the measurement of both BCL6 RNA and protein levels (see p. 129, right column, 2nd and 3rd paragraphs). In summary, the judicial exception is not integrated into a practical application because the steps of (1) administering a generic, un-specified regimen to a patient population and (2) detecting whether genes and/or proteins (SIRT1, BCL6) are overexpressed using well-known methods do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Note that this issue could be addressed by amending the claim to unconditionally require administration of a particular agent.
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.
Scope of Enablement
Claim 1 is 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 diagnosing and treating infertility with the claimed methods, wherein the treatment comprises surgical removal of some or all endometriosis in the subject or administration to the subject of an effective amount of a gonadotropin-releasing hormone (GnRH) agonist, does not reasonably provide enablement for the claims as broadly recited. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Claim 1 recites administration to the subject an effective amount of a BCL6 or SIRT1 inhibitor, or a treatment that “blocks or reduces” BCL6 or SIRT1 “activity”. The instant application discloses generic SIRT1 and BCL6 inhibitors at pages 65-66. The term “inhibitor” encompasses small molecules, antibodies, soluble protein and nucleic acids. Regarding BCL6, Leandro Cerchietti and Ari Melnick (Expert Rev Hematol. 2013; 6: 343-345—on IDS 08/12/2024) teach that a rational design for BCL6 inhibitors would be molecules that “disrupt the BTB domain-corepressor complex” (see p. 2, 3rd paragraph of the Cerchietti Author Manuscript). Cardenas et al. (J Clin Invest. 2016; 126: 3351-3362. doi:10.1172/JCI85795—on IDS filed 08/12/2024) disclose the BCL6 inhibitor FX1 (see p. 3352, right column; discussion at p. 3359). Cardenas et al. teach some of the problems with the prior disclosed BCL6 inhibitors and a method of screening for new inhibitors (see p. 3352, left column, 1st paragraph):
Proof-of-principle studies supporting this strategy [i.e., therapeutic targeting of the BCL6 BTB domain lateral groove as a potential therapy for
B cell lymphomas] involved the development of the peptidomimetic drug RI-BPI, and small-molecule inhibitors of BCL6 such as compound 79-6. However, all of these compounds bind to BCL6 with significantly weaker affinity than endogenous corepressor proteins, which could potentially limit their utility. Herein, we used a novel in silico chemical functional group–based screening approach called SILCS to design compounds that could bind to the BCL6 lateral groove with higher affinity than endogenous corepressors and yet retain specificity for BCL6. (Citations omitted and emphasis added by Examiner).
There is, however, no disclosure in the specification or prior art regarding the structure of the BCL6 inhibitor capable of treating infertility.
Regarding SIRT1, the state of the art is complex and unpredictable. Taguchi et al. (J. Obstet. Gynaecol. Res. 2014; 40: 770-778—on IDS filed 08/12/2024) teach that “[t]here was no significant difference in the expression level of SIRT1 mRNA between ESC [endometriotic stromal cells] and NES [normal endometrial stromal cells] (p. 773, right column, 1st paragraph). In other words, the art suggests that there is no difference in SIRT1 expression between endometriotic and control subjects. Further, Tatone et al. (Oxidative Medicine and Cellular Longevity, 2015, Article ID 659687, http://dx.doi.org/10.1155/2015/659687; 11 pages—on IDS filed 08/12/2024) teach that sirtuin activators, rather than inhibitors, may have a beneficial effect on fertility (see the discussion at pages 3-7 regarding sirtuins and sirtuin activators and their effects on the female reproductive tract). In addition, the post-filing date art of Tatone et al. (Human Reproduction Update, 2018; 24: 267-289—on IDS filed 08/12/2024) teach that sirtuin inhibitors have been known to have negative effects on post-fertilization events (see p. 279, left column, 1st paragraph):
The role of Sirtuins in post-fertilization events has been known since 1994 when the pan-Sirtuin inhibitor NAM was found to inhibit mouse embryo development in vitro. According to this insight, further studies have shown that other Sirtuin inhibitors (i.e. sirtinol, BML-210) induce embryo developmental arrest in murine and porcine IVF embryos. (Citations omitted by Examiner).
In addition, the 2018 article by Tatone and colleagues teach that two years after the effective filing date, sirtuin inhibitors development was still in its infancy:
In contrast with the activators, the Sirtuin inhibitors available so far lack adequate physicochemical characteristics, selectivity for Sirtuin isotype or potency. The best-known endogenous inhibitor of all Sirtuin isotypes is the product of the catalytic reaction of both deacetylation and ADP-ribosylation (i.e. nicotinamide (NAM), along with its structural analogues). Among other low molecular weight inhibitors, sirtinol, a cell-permeable hydroxynaphthaldehyde derivative, exhibits low-potency against SIRT1 and SIRT2, whereas the indole-based EX527 is among the most potent SIRT1-selective inhibitors known so far. (Citations omitted by Examiner).
Although the 2018 article by Tatone et al. discloses one potent SIRT1 inhibitor, the state of the post-filing date art suggests that much more experimentation must be undertaken to develop adequate inhibitors. Further, the art is silent with respect to SIRT1 inhibitors that can be used to treat endometriosis or infertility, particularly since the art suggests that sirtuins may be beneficial for reproductive health.
Although the art provides methods for screening for inhibitors, patent protection is granted in return for an enabling disclosure, not for vague intimations of general ideas that may or may not be patentable. Tossing out the mere germ of an idea does not constitute an enabling disclosure. Reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. See Genentech v. Novo Nordick A/S (CAFC) 42 USPQ2d 1001 (1997). In addition, the teaching of a novel method for generating method of screening disclosed after the filing date of the application cannot provide enablement for the claimed methods. See MPEP § 2164.05(b), which says that the state of the art existing at the filing date of the application is used to determine whether a particular disclosure is enabling as of the filing date.
As noted above, BCL6 and SIRT1 inhibitors may encompass nucleic acids, all of which encompass gene therapy. However, the specification of the instant application does not teach any methods or working examples that indicate inhibition of BCL6 or SIRT1 by administration of antisense RNA and DNA, siRNA, ribozymes, or the like. Jafarlou et al. (Journal of Biological Regulators & Homeostatic Agents, 2016: 30: 315-321—on IDS filed 08/12/2024) teach that progress in gene therapy has been occurring but remains slow and is “still going through its infancy period” (see abstract; sentence bridging left and right columns of p. 319). For example, Jafarlou et al. teach that viral vectors, among the most commonly used vectors in clinical trials, “vary in the capability of transducing different types of cells.”
Further, relevant literature indicates that gene therapy with antisense, siRNA and shRNA is complex. For instance, the extensive review by Hu et al. (Signal Transduction and Targeted Therapy (2020) 5:101) provides background on the current state of the art of siRNA therapy. Hu et al. outline the challenges to siRNA therapy (p. 2, left column, 2nd paragraph):
Although siRNA holds promising prospects in drug development, several intracellular and extracellular barriers limit its extensive clinical application. Naked and unmodified siRNA possesses some disadvantages, such as (1) unsatisfactory stability and poor pharmacokinetic behavior and (2) the possible induction of off-target effects. The phosphodiester bond of siRNA is vulnerable to RNases and phosphatases. Once it is systematically administered into circulation, endonucleases or exonucleases throughout the body will quickly degrade siRNA into fragments, thus preventing the accumulation of intact therapeutic siRNA in the intended tissue. In theory, siRNA only functions when its antisense strand is completely base-paired to the target mRNA. However, a few mismatches are tolerated by the RNA-induced silencing complex (RISC), which may lead to undesired silencing of those genes with a few nucleotide mismatches.
Hu et al. review the techniques undertaken to deal with the challenges of siRNA therapy, which serve to underscore the complexity of the field. For instance, base modification is a promising technique, but one that is “basically at the stage of research and development” (see discussion under “Base modification in the paragraphs bridging the left and right columns of p. 6). Regarding siRNA delivery, Hu et al. teach:
Only 1–2% of internalized LNP [lipid nanoparticle]-loaded siRNAs were released into the cytoplasm, and this only occurred within a limited time frame after internalization. Hence, further understanding the escape mechanism and how to enhance the escape efficiency is of great importance for siRNA drug development (p. 11, left column, 1st paragraph; citations omitted by examiner).
In spite of progress made in the field of siRNA drug development and delivery, Hu et al. underscore the complexity of a field that is still in its developmental stage.
In summary, problems identified early in gene therapy trials regarding successful transfer remain a technological hurdle (see the “Approaches to gene therapy” section bridging pates 317-318 of Jafarlou and colleagues). In view of the teachings of the relevant art, the ability to inhibit BCL6 or SIRT1 genes using any of these RNA or DNA based therapies was not readily available in the relevant art at the time of filing of the instant application, and the limited teachings of the instant application do not overcome these shortcomings.
Due to the large quantity of experimentation necessary to generate the broad genus of BCL6 and SIRT1 inhibitors and testing the same for the ability to treat infertility or endometriosis, the lack of direction/guidance presented in the specification regarding the same, the absence of working examples directed to the same, the complex nature of the invention, and the breadth of the claims which fail to recite limitations on the structure of the recited inhibitors, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Written Description
Claim 1 is 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 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. This is a written description rejection.
In deciding whether the application complies with the written description requirement of 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 1 encompasses methods of treating infertility comprising administering to a subject an effective amount of a BCL6 inhibitor and/or a treatment that blocks or reduces BCL6 activity and/or an effective amount of a SIRT1 inhibitor and/or a treatment that blocks or reduces SIRT1 activity, singly or in any combination. Therefore the claims encompass agents recited in terms of their function. The MPEP 2163(A) states “‘[a]n invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.’” For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. (See MPEP 2163(II)(A)(3)(a)(i)).
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. From the specification, it is clear that Applicant has possession of a subset of generic BCL6 and SIRT1 inhibitors (see pages 65-66 of the instant specification). Nevertheless, the instant specification fails to describe the structure of the recited inhibitors necessary to be capable of treating infertility and endometriosis.
Regarding BCL6, Leandro Cerchietti and Ari Melnick (Expert Rev Hematol. 2013; 6: 343-345; on IDS filed 08/12/2024), teach that a rational design for BCL6 inhibitors would be molecules that “disrupt the BTB domain-corepressor complex” (see p. 2, 3rd paragraph of the Cerchietti Author Manuscript). Cardenas et al. (J Clin Invest. 2016; 126: 3351-3362. doi:10.1172/JCI85795—on IDS filed 08/12/2024) disclose the BCL6 inhibitor FX1 (see p. 3352, right column; discussion at p. 3359) and teach some of the problems with the prior disclosed BCL6 inhibitors and a method of screening for new inhibitors (see p. 3352, left column, 1st paragraph):
Proof-of-principle studies supporting this strategy [i.e., therapeutic targeting of the BCL6 BTB domain lateral groove as a potential therapy for
B cell lymphomas] involved the development of the peptidomimetic drug RI-BPI, and small-molecule inhibitors of BCL6 such as compound 79-6. However, all of these compounds bind to BCL6 with significantly weaker affinity than endogenous corepressor proteins, which could potentially limit their utility. Herein, we used a novel in silico chemical functional group–based screening approach called SILCS to design compounds that could bind to the BCL6 lateral groove with higher affinity than endogenous corepressors and yet retain specificity for BCL6. (Citations omitted and emphasis added by Examiner).
There is, however, no disclosure in the specification or the art regarding the structure of the BCL6 inhibitor capable of treating infertility or endometriosis. Regarding SIRT1, Tatone et al. (Oxidative Medicine and Cellular Longevity, 2015, Article ID 659687, http://dx.doi.org/10.1155/2015/659687, 11 pages—on IDS filed 08/12/2024) teach that sirtuin activators, rather than inhibitors, may have a beneficial effect on fertility (see the discussion at pages 3-7 regarding sirtuins and sirtuin activators and their effects on the female reproductive tract). In addition, the post-filing date art of Tatone et al. (Human Reproduction Update, 2018; 24: 267-289—on IDS filed 08/12/2024) teach that sirtuin inhibitors have been known to have negative effects on post-fertilization events (see p. 279, left column, 1st paragraph).
The generic term “inhibitor” encompasses small molecule, antibody, soluble protein and nucleic acid inhibitors. Neither the specification nor the art provides adequate description of the structure of BCL6 and SIRT1 inhibitors capable of treating infertility. In this case, the only factor present in the claim is the recitation of a BCL6 or SIRT1 inhibitor or a treatment that blocks BCL6 or SIRT1. However, the recitation of this function alone in the claims is little more than a wish for possession and does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing “a result that one might achieve if one made that invention”); In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does ‘‘little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”). Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Notice for all US Patent Applications filed on or after March 16, 2013: 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 § 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 1 is rejected under 35 U.S.C. 103 as being unpatentable over Young et al. (WO2015/143228, filed 19 March 2015—on IDS filed 08/12/2024) in view of the Lessey abstract (Reproductive Sciences, (March 2015) Vol. 22, Supp. 1, pp. 223A. Abstract Number: F-058—on IDS filed 08/12/2024) and Boniface et al. (US20140287948—on IDS filed 08/12/2024). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Young et al. teach a method of diagnosing and treating infertility in a subject, comprising:
(a) obtaining a sample of endometrium from the mammal;
(b) detecting a level of expression of a BCL6 gene product in the sample;
(c) correlating the expression level of the BCL6 gene product in the sample with endometrial receptivity, wherein overexpression of the BCL6 gene product in the sample as compared to expression of the BCL6 gene product in a sample of similarly timed endometrium isolated from a normally fertile control subject is indicative of reduced receptivity of the endometrium in the subject; and
(d) determining whether the subject is a candidate for implantation of an embryo based on the correlating step.
See p. 2, line 19 - p. 3, line 11; claims 26-31 of Young et al. Young et al. also teach a method of diagnosing and treating endometriosis in a subject. The method of detecting the presence of endometriosis in a subject comprises:
(a) providing a sample of endometrium from a subject;
(b) detecting a level of expression of a BCL6 gene product in the sample; and
(c) correlating the expression level of the BCL6 gene product in the sample with the presence of endometriosis in the subject, wherein overexpression of the BCL6 gene product in the sample as compared to expression of the BCL6 gene product in a sample of similarly timed endometrium isolated from a normal control subject is indicative of the presence of endometriosis in the subject.
See p. 6, line 19 through p. 7, line 8; claims 32-38 and 54-57 of Young et al. Young et al. teach treatment with GnRH or surgical removal of endometrial tissue (claims 31; 55).
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Young et al. do not teach the detection of SIRT1 gene and/or protein. The Lessey abstract teaches that SIRT1 protein is overexpressed in endometrial tissue of women undergoing surgical resection treatment of endometriosis (see abstract under “RESULTS”). Further, the Lessey abstract teaches that surgical removal of endometriotic tissue “remarkably reduced” SIRT1 expression (see abstract under “RESULTS”). In addition, the Lessey abstract teaches that “SIRT1 was increased in the eutopic endometrium” in a baboon animal model during disease progression (see abstract under “RESULTS”). Thus, in summary, the Lessey abstract teaches 1) SIRT1 is overexpressed in endometriosis, 2) SIRT1 expression increases during progression of endometriosis and 3) removal of endometriotic tissue results in a remarkable reduction of SIRT1. See the “RESULTS” section of the Lessey abstract.
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of Young et al. by measuring SIRT1, as taught in the Lessey abstract because the Lessey abstract teaches that SIRT1 protein is over-expressed in the same patient population. See also Boniface et al., who teach that proteins that are differentially expressed between cases and controls are appropriate biomarkers (see abstract; paragraph [0023] of the PGPUB). Further, when devising a diagnostic method, the person of ordinary skill in the art would have been motivated to add an additional biomarker because Young et al. suggest that more than one biomarker can be used (see p. 23, last paragraph). Further, Boniface et al. teach that panels combining biomarkers have a high degree of specificity and sensitivity (see paragraph [0023] of the PGPUB).
In addition, the person having ordinary skill would have been motivated because the Lessey abstract teaches that SIRT1 expression was a sensitive measure that increased during endometriosis progression, but that was “remarkably reduced after surgical excision of endometriosis”, suggesting that SIRT1 tracks with disease progression and regression. The person of ordinary skill in the art could have reasonably expected success because the Lessey abstract taught that SIRT1 tracked with disease progression and regression and would therefore be a sensitive measure for endometriosis. Given what was already known in the art at the time of the filing of the invention concerning the relationship between endometriosis and infertility and the suitability of SIRT1 as a biomarker, the person having ordinary skill in the art would have expected that adding SIRT1 as a biomarker would result in an improvement in the ability to diagnose and treat endometriosis and infertility. It is logical to combine two sensitive biomarkers associated with the same disease when devising a diagnostic assay.
Thus, the claims do not contribute anything non-obvious over the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,474,105. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. In both cases the claims are drawn to diagnosis and treatment comprising the steps of:
a) obtaining a sample from the subject;
b) determining a level of expression of a SIRT1 protein in the sample;
c) determining a level of expression of a BCL6 protein in the sample;
d) comparing the level of expression determined in (b) with the level of expression of a SIRT1 protein in a sample obtained from a control subject or a population of control subjects;
e) comparing the level of expression determined in (c) with the level of expression of a BCL6 protein in a sample obtained from a control subject or a population of control subjects;
f) diagnosing the subject as having decreased endometrial receptivity due to overexpression of a SIRT1 protein and a BCL6 protein when the subject has a level of expression of the SIRT1 protein greater than the level of expression of the SIRT1 protein of the control subject or population of control subjects and also has a level of expression of the BCL6 protein that is greater than the level of expression of the BCL6 protein of the control subject or population of control subjects; and
g) treating the subject having overexpression of a SIRT1 protein and a BCL6 protein by surgical removal of some or all of any endometriosis in the subject, administration to the subject of an effective amount of a gonadotropin-releasing hormone (GnRH) agonist, or any combination thereof, thereby increasing the likelihood of implantation of an embryo in the subject.
The differences between the claim sets are as follows. The claims of the reference patent are more specific regarding the causes/symptoms of infertility (i.e., increasing the likelihood of implantation of an embryo; managing recurrent pregnancy loss; increasing endometrial receptivity, etc.), however the more specific recitation in the claims of the reference patent anticipate the more general recitation in the instant claims (“infertility”).
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,234,465 in view of the Lessey abstract and Boniface et al. Both references are cited above. The claims of the reference patent teach diagnosing and treating endometriosis based upon measurement of BCL6 levels comprising the steps of:
a) obtaining a sample of endometrium from the subject during the second half of the subject's menstrual cycle;
b) detecting a level of expression of a BCL6 gene product in the sample;
c) comparing the level of expression detected in (b) with the level of expression of a BCL6 gene product in a sample of endometrium obtained from a control subject during the second half of said control subject's menstrual cycle;
d) diagnosing the subject as having endometriosis when the subject has a level of expression of the BCL6 gene product that is greater than the level of expression of the BCL6 gene product of the control subject; and
e) treating the endometriosis in the subject that has been diagnosed as having endometriosis by surgical removal of some or all of the endometriosis, administration to the subject of an effective amount of a gonadotropin-releasing hormone (GnRH) agonist, or any combination thereof.
The claims of the reference patent do not recite diagnosis and/or treatment of infertility per se, but endometriosis is a major underlying cause of infertility in females, and therefore represents a species of patients affected by infertility. Thus, endometriosis is a species of infertility, and the species recited in the claims of the reference patent anticipates the genus recited in the instant claims. In addition, the claims of the reference patent do not recite measurement of SIRT1. The Lessey abstract teaches that SIRT1 protein is overexpressed in endometrial tissue of women undergoing surgical resection treatment of endometriosis (see abstract).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the claims of the reference patent by measuring SIRT1, as taught in the Lessey abstract because the Lessey abstract teaches that SIRT1 protein is over-expressed in the same patient population. See also Boniface et al., who teach that differentially expressed proteins make good biomarkers (see abstract; paragraph [0023] of the PGPUB). When devising a diagnostic method, the person of ordinary skill in the art would have been motivated to add an additional biomarker because the Lessey abstract teaches that SIRT1 was a sensitive measure of endometriosis that was “remarkably reduced after surgical excision of endometriosis”. Further, Boniface et al. teach that panels combining biomarkers have a high degree of specificity and sensitivity (see paragraph [0023] of the PGPUB). For these reasons as well, the person of ordinary skill in the art could have reasonably expected success; he or she would be confident that the biomarker was a sensitive measure for endometriosis based upon the Lessey abstract. Given what was already known in the art at the time of the filing of the invention concerning the relationship between endometriosis and infertility and the suitability of SIRT1 as a biomarker, the person having ordinary skill in the art would expect that adding SIRT1 as a biomarker would result in an improvement in the ability to diagnose and treat endometriosis and infertility.
Conclusion
Claim 1 is rejected.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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