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 .
Priority
This application is a 371 of PCT/IB2022/062870 12/29/2022 which claims benefit of 63/294,418 12/29/2021. Based on the filing receipt, the effective filing date of this application is December 29, 2021 which is the filing date of 63/294,418 from which the benefit of priority is claimed.
Status of Claims
Claims 1, 3-10, 12-22 are pending and examined herein.
Claims 2 and 11 are cancelled.
Claim Objections
Claim 9 is objected to because of the following informalities:
Claim 9 recites, “The method of claim 7, wherein a greater decrease in progerin
concentration indicates an greater increase in life expectancy”. The claim should recite, “The method of claim 7, wherein a greater.
Appropriate correction is required.
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.
Claims 1, 3-10, 12-22 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.
Claims 1, 3-10, 12-22 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
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. 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: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
The claims are directed to a “quantitative immunoassay [that] detects progerin but does not detect wildtype lamin A protein” (claims 1, 10, and 18), “a progerin specific detection antibody comprising a detectable label, thereby binding the captured progerin but not the captured lamin A with the detection antibody” (claims 3 and 13), and “a capture antibody that binds to both wildtype lamin A and progerin” (claim 3 and 13). The claims impose no restriction on the size or structure of the antibodies other than their binding specificity.
The scope of the claims therefore covers methods comprising a large genus of antibodies characterized by substantial variability.
Regarding the predictability or unpredictability in the art, antibodies can often be functionally promiscuous or multi-specific which can lead to antibodies binding to more than one antigen, as evidenced by Jain (“Antibody specificity and promiscuity”, published 2019-02-05). Due to multi-specificity and challenges related to specificity, antibodies have a level of unpredictability that requires the applicant to provide evidence that they have considered a sufficient number of antibodies.
The specification does not disclose the reduction to practice of a sufficient number of specific antibodies having the necessary functional characteristics. The specification discloses, “Immunoassays for use in the described methods employ antibodies that specifically recognize lamin A and progerin. Such antibodies can be monoclonal or polyclonal. Particular examples of antibodies for use in the described methods include intact immunoglobulins and the variants and portions thereof that are well known in the art, such as Fab' fragments, F(ab )'2 fragments, single chain Fv proteins ("scFv"), and disulfide stabilized Fv proteins ("dsFv").
More than specific structure or molecular arrangement, antibodies for use in the described method must be able to specifically bind to lamin A and progerin ( capture antibodies) or bind specifically to progerin but not lamin A (detection antibodies). The terms "bind specifically" and "specific binding" refer to the ability of an antibody to bind to a target molecular species in preference to binding to other molecular species with which the specific binding agent and target molecular species are admixed. A specific binding agent is said specifically to recognize a target molecular species when it can bind specifically to that target.
[…] Antibodies for use in the described methods are commercially available” (see, p. 9-10 of applicant’s specification). The applicant suggests art-recognized methods of using antibodies and provides prophetic examples. The applicant provides one example of a set of specific antibodies with the claimed functional characteristics, “Briefly, the progerin capture antibody (mouse Mab anti-Lamin A+C, clone: 131C3 Abcam, epitope between amino acid residues 319-566, common to Lamins A, C and progerin) was coated onto MP at 25 μg antibody/mg MP.
[...] Next, fluorescently labeled progerin-specific detection antibody (Mouse Mab, clone: 13A4, from Millipore, epitope between amino acids 604 and 611 of progerin, which cross the deletion region of lamin A)” (see, p. 17, lines 11-17 of the applicant’s specification). However, considering the vast genus of antibodies claimed by the invention, there is insufficient disclosure of antibodies falling within the claimed genus.
The disclosure of general methods that use antibodies is insufficient to describe the claimed broad genus of antibodies. The Federal Circuit addressed an analogous situation in University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004), finding that disclosure of “assays for screening compounds, including peptides, polynucleotides, and small organic molecules to identify those that inhibit the expression or activity of the PGHS-2 gene product,” did not satisfy the written description requirement for claims requiring administration of a “compound that selectively inhibits PGHS-2.” Rochester, 119 F.3d at 918, 927; see also Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company, 598 F.3d 1336, 1344 (Fed. Cir. 2010) (recognizing distinction between requirements for written description and enablement).
Furthermore, there is also no disclosure of any partial structure common to the members of the genus of antibodies that would correlate with function (in this case, the claimed functions of selectively binding to “both wildtype lamin A and progerin” or “binding the captured progerin but not the captured lamin A”).
The importance of structure/function correlations was recently highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centocor Biologics, App. No. 2013-1338, -1346 (Fed. Cir., July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002).
There is no partial structure or other identifying characteristics disclosed, common to the members of the genus of antibodies having sufficiently high binding affinity, that would allow one skilled in the art to envision that Appellant has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus.
For all of these reasons, the specification does not demonstrate possession of the entire genus of antibodies having the claimed functional characteristics of specifically binding to “both wildtype lamin A and progerin” or “binding the captured progerin but not the capture lamin A”.
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.
Claim 9 is 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.
The term “greater” in claim 9 is a relative term which renders the claim indefinite. The term “greater” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “greater” modifies the decrease in progerin concentration and the increase in life expectancy. Therefore, the metes and bounds of the claim cannot be ascertained. For the purpose of applying prior art, claim 9 will be interpreted as “The method of claim 7, wherein a .
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 1, 3-10, 12-15, and 18-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Regarding claims 1, 3-10, 12-15, and 18-20, the independent claims recite a “method for prognosis of Hutchinson-Gilford progeria syndrome (HGPS) in a subject” (claim 1), a “method for determining the efficacy of a treatment for Hutchinson-Gilford progeria syndrome (HGPS)” (claim 10), and a “method for treatment of Hutchinson-Gilford progeria syndrome (HGPS) in a subject” (claim 18). All of the independent claims are directed at the relationship between progerin and HGPS. These judicial exceptions are not integrated into a practical application, such as constituting an improvement in the technological field, or including steps recited in addition to the judicial exception that integrates detection of the natural phenomena into a particular treatment/prophylaxis according to MPEP § 2106.04(d)(2). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because the additional elements fail to provide either an inventive concept or impose meaningful limits upon the method such that the invention does not preempt every observance of the natural phenomenon itself.
The claims are also directed at another judicial exception, the following abstract ideas, namely mental processes: “comparing the concentration of progerin in the sample with an HGPS-positive control” (claim 1), “comparing the pre-treatment concentration of progerin with the post-treatment concentration of progerin” (claim 10), and “comparing the concentration of progerin in the sample with an HGPS-positive control” (claim 18). “Comparing” is an abstract idea, namely a mental process that could be performed in a practitioner’s head, or with a practitioner with pen and paper.
Eligibility Step 1:
Claims 1, 3-10, 12-15, and 18-20 are directed to methods comprising measuring progerin to assess the status of a patient with HGPS. Methods are one of the eligible statutory categories for invention (STEP 1: YES). However, eligibility of the claims is not self-evident, and therefore analysis must proceed to Step 2.
Eligibility Step 2A, Prong One:
The natural relationships to which the claims are directed (i.e. the relation between the level of the biomarker progerin and HGPS) are laws of nature. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring levels of biomarkers comprising progerin in a biological sample and the status of HGPS. Therefore, the claims recite at least one judicial exception (STEP 2A, Prong One: YES).
The claims also recite the following limitations: “wherein a concentration of progerin in the sample that is below the concentration of progerin in the HGPS-positive control indicates an increased life expectancy in the subject” (claim 1), “wherein a decrease in progerin concentration following the treatment indicates increased life expectancy” (claim 7), “wherein the decrease in progerin concentration following the treatment is between 35-62%” (claim 8), “wherein a greater decrease in progerin concentration indicates an [sic] greater increase in life expectancy” (claim 9), and “wherein a continued or further decrease in progerin concentration indicates continued efficacy of the treatment” (claim 12). These claim limitations are all directed at the natural relationship between progerin and HGPS. The claims are only further specifying the features of the natural relationship.
Eligibility Step 2A, Prong Two:
According to Step 2A, Prong Two, set forth in MPEP 2106.04 II A (2), the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. This analysis turns to the additional steps/elements recited within the claims. In independent claim 18, the additional steps are “if the subject has HGPS, administering to the subject a treatment for HGPS that lowers progerin concentration”.
Regarding the additional steps cited in claim 18, the “treatment for HGPS” is recited at a high level of generality and is not tied, for example to any particular treatment. The treatment or prophylaxis limitation must be “particular,” i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). See MPEP 2106.04(d)(2).
Regarding claims 1, 3-10, 12-15, and 18-20, providing samples/controls and quantitating biomarker levels using methods with specific limits of quantitation are insufficient to integrate the judicial exception because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Furthermore, the steps of measuring biomarkers are recited at a high level of generality and are not tied, for example, to any particular machine or apparatus.
There are no additional elements that reflect an actual improvement within the technical field. For example, there are no additional elements that apply the natural correlation/phenomena judicial exception to a particular treatment or which utilize a particular machine; there are no additional elements that effect a transformation; and, there are no additional elements that apply the judicial exception in some other meaningful way beyond generally linking it to a field, namely, HGPS. In this way the claims, as drafted, do not integrate the judicial exception into a practical application that would overcome monopolizing the exception. (STEP 2A, Prong Two: NO).
Eligibility Step 2B:
Lastly, there are no additional elements of claims 1, 3-10, and 12-15, and 18-20.
Therefore, the steps/elements recited in addition to the judicial exception do not add significantly more (STEP 2B: NO).
The claimed steps/elements recited in addition to the judicial exception, alone or in combination, do not make an inventive contribution over the methods that were known in the art prior to filing, and they amount to mere observation of the natural phenomenon itself, by any means known, with the words “apply it” in order to append it to the field of HGPS.
For all of these reasons, the claimed subject matter is ineligible under 35 U.S.C. 101 because the claims are directed to a natural phenomenon judicial exception without significantly more.
However, it is noted that claims 16-17 and 21-22 do integrate the judicial exception into a practical application by tying the quantitation of progerin in a sample from a subject to treatment with a particular treatment, farnesyl transferase inhibitors.
Claim Rejections - 35 USC § 102
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.
Claims 1 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McClintock (“The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin”, published 2007).
With respect to claim 1, McClintock teaches a method for prognosis of Hutchinson-Gilford progeria syndrome (HGPS) in a subject, comprising:
providing a sample from a subject;
quantitating the concentration of progerin in in the sample with a quantitative
immunoassay, wherein the quantitative immunoassay detects progerin but does not detect
wildtype lamin A protein; and
comparing the concentration of progerin in the sample with an HGPS-positive
control, wherein a concentration of progerin in the sample that is below the concentration
of progerin in the HGPS-positive control indicates an increased life expectancy in the subject (see, e.g., sample from a subject – p. 1, under “Abstract”: “Screening 150 skin biopsies”; quantitating the concentration of progerin in in the sample with a quantitative
immunoassay, wherein the assay does not detect wildtype lamin A protein– p. 3, col. 1, para. 2: “The serum of rabbit 972 specifically recognized progerin protein and gave no signal with A-type lamin including pre-lamin A”, and p. 2, under “Figure 1.”, panel “C”, and p. 5, under “Figure 3.”; comparing the concentration of progerin in the sample with an HGPS-positive control – p. 2, under “Figure 1.”). The applicant’s specification identifies immunofluorescent histochemistry as an immunoassay that can be used with methods (see, p. 9, lines 21-23).
With respect to claim 4, McClintock teaches wherein the control is from the same subject at an earlier time point, as in claim 4 (see, e.g., p. 4, col. 1, para. 1: “fibroblast culture
DR118 established from an 86 year-old female was monitored by indirect immunofluorescence with anti-progerin mAb and exhibited an average of 0.4% of progerin-positive cells in young cultures. That average increased to 0.8% in late cultures (PPDs 30 to 35)”).
Claims 10 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cao (“Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein Clearance in Hutchinson-Gilford Progeria Syndrome Cells”, published 2011).
With respect to claim 10, Cao teaches a method for determining the efficacy of a treatment for Hutchinson-Gilford progeria syndrome (HGPS), comprising:
providing a pre-treatment sample from a subject, that is taken prior to
administration of a treatment for HGPS;
determining the concentration of progerin in the pre-treatment sample with a
quantitative immunoassay, wherein the quantitative immunoassay detects progerin but
does not detect wildtype lamin A protein;
providing a post-treatment sample from the subject, that is taken during or after
administration of a treatment for HGPS;
determining the concentration of progerin in the post-treatment sample with the
quantitative immunoassay; and
comparing the pre-treatment concentration of progerin with the post-treatment
concentration of progerin, wherein a significant decrease in progerin concentration in the
post-treatment sample indicates that the treatment is effective (see, e.g., p. 3, col. 1, para. 1: “we generated a custom antibody against progerin using a peptide located at the cryptic splicing junction as an antigen (anti-progerin). This antibody specifically recognized progerin, but not lamin A or C in Western (immuno) blotting and immunofluorescence analyses (fig. S4). When normalized with a β-actin control, quantification of protein by Western blot revealed a ~50% reduction in progerin amounts in rapamycin-treated HGPS cells on day 60 of treatment relative to mock-treated cells”, and p. 4, under “Fig. 2.”, panels “A.” and “B.”).
With respect to claim 12, Cao teaches further comprising providing one or more additional post-treatment samples that are taken from the subject at time points subsequent to the initial post-treatment sample, and wherein a continued or further decrease in progerin concentration indicates continued efficacy of the treatment (see, e.g., p. 6, under “Fig. 4.”, panel “A.”).
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 3 is rejected under 35 U.S.C. 103 as being unpatentable over McClintock (cited above), as applied to claims 1 and 4 above, and further in view of Todd (“Ultrasensitive Flow-based Immunoassays Using Single-Molecule Counting”, published 2007).
McClintock teaches as set forth above, but fails to teach wherein the quantitative immunoassay comprises:
contacting the sample with a capture antibody that binds to both wildtype lamin A
and progerin, resulting in a mixture of captured lamin A and captured progerin;
separating the mixture of captured lamin A and captured progerin from the
sample;
contacting the mixture of captured lamin A and captured progerin with a progerin specific detection antibody comprising a detectable label, thereby binding the captured
progerin but not the captured lamin A with the detection antibody;
separating the detectable label from the mixture with captured lamin A; and
detecting the detectable label, and thereby quantitating the amount of progerin in
the sample, as in claim 3.
Todd teaches an assay method wherein the quantitative immunoassay comprises:
contacting the sample with a capture antibody that binds to the target;
separating the mixture of target from the sample;
contacting the mixture of target with a specific detection antibody comprising a detectable label, thereby binding the captured target with the detection antibody;
separating the detectable label from the mixture; and
detecting the detectable label, and thereby quantitating the amount of target in
the sample, as in claim 3 (see, e.g., p. 1991, col. 1, under “ERRENA IAs”: “Samples or calibrators (in volumes of 50–100 L) were diluted with assay buffer containing capture antibody-coated MPs (e.g., in 150 L) and incubated in a 96-well plate for 1–2 h at 25 °C with shaking. All plasma or serum samples were tested undiluted without pretreatment. MPs were separated using a magnetic bed (Ambion). Supernatant was removed, MPs were washed once, and then 20 L detection antibody (50–500 mg/L diluted in assay buffer) was added and incubated for 60 min at 25 °C with shaking. The MPs were again magnetically separated and washed 6 times using Tris-buffered saline with 0.5 mL Triton X-100/L. After removal of residual wash buffer, 20 L elution buffer (4 mol/L urea) was added. This reagent disrupted antibody–analyte interactions and resulted in the release of detection antibody from the MPs. The solution in each 96-well plate was then transferred to a 384-well filter plate (0.2 m, AcroPrep cat. no. 5070, Pall) and centrifuged at 1200g for 3 min to separate detection antibody in elution buffer from MPs. The eluted and filtered material in the 384-well plate was then placed into the Erenna Immunoassay System”).
McClintock and Todd are analogous to the field of the claimed invention because they are both in the field of immunoassays for scarce proteins. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the quantitative immunoassay of Todd in the methods of McClintock. An artisan would have been motivated to do so because Todd discloses, “the Erenna Immunoassay System builds single-molecule detection combined with MP IA technology to provide highly sensitive IAs. This system also provides a broad dynamic reporting range and flexible sample volume requirements. The flexibility of sample volume may allow determination of multiple quantifications from a small sample or to conserve samples” (see, Todd, p. 1994, col. 2, para. 4). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over McClintock as applied to claims 1 and 4 above, and further in view of Cao (cited above) and Gordon (“Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome”, published 2018).
McClintock teaches as set forth above, but fails to teach repeating the method one or more times after the subject undergoes a treatment for HGPS, wherein a decrease in progerin concentration following the treatment indicates increased life expectancy, as in claims 7-9.
However, Cao teaches repeating the measurement of progerin after treatment for HGPS, wherein the decrease in progerin following treatment is 50%, as in claims 7-9 (see, e.g., p. 3, col. 1, para. 1: “we generated a custom antibody against progerin using a peptide located at the cryptic splicing junction as an antigen (anti-progerin). This antibody specifically recognized progerin, but not lamin A or C in Western (immuno) blotting and immunofluorescence analyses (fig. S4). When normalized with a β-actin control, quantification of protein by Western blot revealed a ~50% reduction in progerin amounts in rapamycin-treated HGPS cells on day 60 of treatment relative to mock-treated cells”, and p. 4, under “Fig. 2.”, panels “A.” and “B.”, and p. 1, under abstract: “Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS”).
Furthermore, Gordon teaches increased life expectancy following treatment of HGPS, as in claims 7-9 (see, e.g., p. 1687, under “CONCLUSIONS AND RELEVANCE”: “Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up”).
McClintock, Cao, and Gordon are analogous to the field of the claimed invention because they are all in the field of HGPS. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to repeat the measurements of McClintock after treatment because Cao discloses that progerin decreases after HGPS treatment and increases longevity (see, Cao, p. 1, under abstract: “Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS”) and Gordon discloses, “Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up” (see, Gordon, p. 1687, under “CONCLUSIONS AND RELEVANCE”). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Cao (cited above), as applied to claims 10 and 12 above, and further in view of Todd (cited above).
Cao teaches as set forth above, but fails to teach wherein the quantitative immunoassay comprises:
contacting the sample with a capture antibody that binds to both wildtype lamin A
and progerin, resulting in a mixture of captured lamin A and captured progerin;
separating the mixture of captured lamin A and captured progerin from the
sample;
contacting the mixture of captured lamin A and captured progerin with a progerin specific detection antibody comprising a detectable label, thereby binding the captured
progerin but not the captured lamin A with the detection antibody;
separating the detectable label from the mixture with captured lamin A; and
detecting the detectable label, and thereby quantitating the amount of progerin in
the sample, as in claim 13.
Todd teaches an assay method wherein the quantitative immunoassay comprises:
contacting the sample with a capture antibody that binds to the target;
separating the mixture of target from the sample;
contacting the mixture of target with a specific detection antibody comprising a detectable label, thereby binding the captured target with the detection antibody;
separating the detectable label from the mixture; and
detecting the detectable label, and thereby quantitating the amount of target in
the sample, as in claim 13 (see, e.g., p. 1991, col. 1, under “ERRENA IAs”: “Samples or calibrators (in volumes of 50–100 L) were diluted with assay buffer containing capture antibody-coated MPs (e.g., in 150 L) and incubated in a 96-well plate for 1–2 h at 25 °C with shaking. All plasma or serum samples were tested undiluted without pretreatment. MPs were separated using a magnetic bed (Ambion). Supernatant was removed, MPs were washed once, and then 20 L detection antibody (50–500 mg/L diluted in assay buffer) was added and incubated for 60 min at 25 °C with shaking. The MPs were again magnetically separated and washed 6 times using Tris-buffered saline with 0.5 mL Triton X-100/L. After removal of residual wash buffer, 20 L elution buffer (4 mol/L urea) was added. This reagent disrupted antibody–analyte interactions and resulted in the release of detection antibody from the MPs. The solution in each 96-well plate was then transferred to a 384-well filter plate (0.2 m, AcroPrep cat. no. 5070, Pall) and centrifuged at 1200g for 3 min to separate detection antibody in elution buffer from MPs. The eluted and filtered material in the 384-well plate was then placed into the Erenna Immunoassay System”).
Cao and Todd are analogous to the field of the claimed invention because they are both in the field of immunoassays for scarce proteins. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the quantitative immunoassay of Todd in the methods of Cao. An artisan would have been motivated to do so because Todd discloses, “the Erenna Immunoassay System builds single-molecule detection combined with MP IA technology to provide highly sensitive IAs. This system also provides a broad dynamic reporting range and flexible sample volume requirements. The flexibility of sample volume may allow determination of multiple quantifications from a small sample or to conserve samples” (see, Todd, p. 1994, col. 2, para. 4). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Cao (cited above), as applied to claims 10 and 12 above, and further in view of Gordon (cited above).
Cao teaches as set forth above, but fails to teach the treatment comprises a farnesyl transferase inhibitor, specifically lonafarnib, as in claims 16-17.
Gordon teaches treating HGPS patients with lonafarnib monotherapy, as in claims 16-17 (see, e.g., p. 1687, under “CONCLUSIONS AND RELEVANCE”: “Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up”).
Cao and Gordon are analogous to the field of the claimed invention because they are both in the field of HGPS. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the treatment of Gordon in the method of Cao. An artisan would have been motivated to do so because Gordon teaches “Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up” (see, p. 1687, under “CONCLUSIONS AND RELEVANCE”). An artisan would have understood the benefit of lonafarnib treatment, mainly the lower mortality rate. An artisan would have had a reasonable expectation of success based on the given disclosures.
Claims 18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over McClintock (cited above), as applied to claims 1 and 4 above, and further in view of Gordon (cited above).
McClintock teaches as set forth above, including providing a sample from a subject;
quantitating the concentration of progerin in in the sample with a quantitative
immunoassay, wherein the quantitative immunoassay detects progerin but does not detect
wildtype lamin A protein;
comparing the concentration of progerin in the sample with an HGPS-positive
control, wherein if the concentration of progerin in the sample indicates that the subject
has HGPS, as in claim 18 (see, e.g., sample from a subject – p. 1, under “Abstract”: “Screening 150 skin biopsies”; quantitating the concentration of progerin in in the sample with a quantitative
immunoassay, wherein the assay does not detect wildtype lamin A protein– p. 3, col. 1, para. 2: “The serum of rabbit 972 specifically recognized progerin protein and gave no signal with A-type lamin including pre-lamin A”, and p. 2, under “Figure 1.”, panel “C”, and p. 5, under “Figure 3.”; comparing the concentration of progerin in the sample with an HGPS-positive control – p. 2, under “Figure 1.”). The applicant’s specification identifies immunofluorescent histochemistry as an immunoassay that can be used with methods (see, p. 9, lines 21-23).
But, McClintock fails to teach a method for treatment of Hutchinson-Gilford progeria syndrome (HGPS) in a subject, comprising:
if the subject has HGPS, administering to the subject a treatment for HGPS that
lowers progerin concentration, as in claim 18. McClintock also fails to teach the treatment comprises a farnesyl transferase inhibitor, specifically lonafarnib, as in claims 21-22.
Gordon teaches treating HGPS patients with lonafarnib monotherapy, as in claims 18 and 21-22 (see, e.g., p. 1687, under “CONCLUSIONS AND RELEVANCE”: “Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up”).
McClintock and Gordon are analogous to the field of the claimed invention because they are both in the field of HGPS. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the treatment of Gordon in the method of McClintock. An artisan would have been motivated to do so because Gordon teaches “Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up” (see, p. 1687, under “CONCLUSIONS AND RELEVANCE”). An artisan would have understood the benefit of lonafarnib treatment, mainly the lower mortality rate. An artisan would have had a reasonable expectation of success based on the given disclosures.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-10, 12-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9, and 11-20 of U.S. Patent Application No. 18/595,507 (hereto referred to as ‘507). Although the claims at issue are not identical, they are not patentably distinct from each other because the only difference is that HGPS is substituted with “a progerin-related aging pathology” in ‘507. HGPS is the dominant progerin-related aging pathology. The name for the protein progerin comes from the Hutchinson-Gilford progeria syndrome.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
While claims 5-6, 14-15, and 19-20 are free of the prior art, the claims are rejected under 35 U.S.C. 112(b), 35 U.S.C. 101, and for non-statutory double patenting.
While McClintock (cited above), Cao (cited above), and Gordon (cited above) teach as set forth above, they all fail to teach the lower limit of quantitation of the quantitative immunoassay is 59 pg/ml and the upper limit of quantitation of the quantitative immunoassay is 30,000 pg/ml, as in claims 5-6, 14-15, and 19-20.
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/MICHAEL CAMERON SVEIVEN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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