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
The Preliminary Amendment filed 05/21/24 is acknowledged and has been entered. Claims 3, 5-6, 15, 21, 24-27 and 20-49 have been canceled. Claims 22-23 have been amended. Accordingly, claims 1-2, 4, 7-14, 16-20, 22-23 and 28-29 are pending and under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1, step (a) the recitation “a subject receiving HCT” should be --the subject receiving HCT--.. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: Claim 2 is objected to because of improper wording of a Markush-type claim. The recitation “wherein the therapeutic agent is” should be --wherein the therapeutic agent is selected from the group consisting of--.
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.
Written Description
Claims 1-2, 4, 7-14, 16-20, 22-23 and 28 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed a method of preventing sinusoidal obstructive syndrome (SOS) in a subject receiving hematopoietic stem cell transplantation (HCT).
The specification on page , lines 1-5 discloses that the present disclosure provides methods for treating and/or preventing sinusoidal obstructive syndrome (SOS). The specification on page 29, lines 7-15 discloses that six out of the ten patients diagnosed with SOS received defibrotide while the other patients were not able to receive the treatment due to contraindications, particularly bleeding. This highlights the importance of early diagnosis based on revised criteria and early intervention (15,
16, 34). Five of the SOS patients died within 100 days. In two randomized trials of defibrotide for the prevention of SOS, OS was not different between placebo and defibrotide groups (10, 11). The three markers were further tested as potential monitoring markers of response to defibrotide treatment and showed a trend towards normalization to non-SOS patient levels as early as 7 days post-treatment. If validated in a larger cohort, it could potentially justify defibrotide treatment for shorter time course than the current 21 days. However, the specification does not provide any data, graphs, examples, experiments to show the prevention of SOS. The term “prevent” (recited in claim 1) is interpreted as implying an absolute and complete prevention of the appearance/onset of SOS, i.e., not any overt symptom or pre-symptomatic marker or damage may be present at any level. The specification fails to reasonably provide written description for prophylaxis (prevention) of SOS. It is recommended to delete the term from the claims.
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 1-2, 4, 7-14, 16-20, 22-23 and 28 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, step (d) the recitation “said patient” is vague and indefinite because it is unclear if the applicant is referring to the subject recited in step (a) or if the applicant intends something else. Please clarify.
Claim 17 the recitation “a subject” is vague and indefinite because it is unclear if the applicant is referring to the subject recited in claim 1 or if the applicant intends another subject. See also deficiencies found in claims 18-19.
Claim 20 is vague and indefinite because the claim depends from claim 3 and claim 3 has been canceled. Therefore it is unclear which claim, claim 20 should depend from. Please clarify.
Claim 22 is vague and indefinite because the claim depends from claim 3 and claim 3 has been canceled. Therefore it is unclear which claim, claim 22 should depend from. Please clarify.
Claim 28 the recitation “a subject” is vague and indefinite because it is unclear if the applicant is referring to the subject recited in claim 1 or if the applicant intends another subject. Please clarify.
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.
NOTE: Claim 1 as currently recited allows for an embodiment wherein only on of the biomarkers has to show an elevation for the diagnosis because the claim recites an “or” situation. Therefore, only one of the three recited biomarkers meets the limitations of the claim.
Claims 1-2, 4, 7-14, 20 and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Paczesny (US 2017/0248612).
Paczesny discloses a method of diagnosing and treating sinusoidal obstruction syndrome (SOS) in a subject early after hematopoietic stem cell transplantation (e.g. abstract, para’s 0011, 0022, 0033). Paczesny discloses measuring at least one of ST2, L-Ficolin and HA in a biological samples from the subject with a specific binding agent that specifically binds to the biomarker, wherein the specific binding agent forms a complex with the biomarker; and detecting the agent-biomarker complex, thereby determining the biomarker expression level; wherein an elevated level compared to a sample from a control is indicative of the SOS (e.g. para 0011) and treating the subject having SOS (e.g. abstract, para’s 0022, 0033). Paczesny discloses that the biomarkers can be measured by performing an ELISA using antibodies specific for the biomarkers (e.g. para’s 0058-0059). Paczesny teaches to obtain the blood sample in patients receiving HCT to measure HA, ST2 or L-ficolin at days 1-21 (e.g. para 0040). Paczesny also teaches that a subjects age for testing the sample can be ages 1-58 (e.g. page 6, Table 2). Paczesny teaches that the subject identified as having SOS can be treated with a therapeutic agent such as defibrotide (e.g. para’s 0003, 0007, 0022, 0033, 0102-0103). Paczesny teaches an AUC of each of the biomarkers is greater than 0.5 (e.g. para 0014). Paczesny teaches the method can be for the prognosis wherein a level can be indicative of decreased survival as compared to median survival in the subject (e.g. para’s 0012, 0035).
With respect to claim 20 as currently recited. The Paczesny teach the same subjects and same therapeutic agent as currently recited and therefore absent evidence to the contrary the defibrotide would result in increased expression levels of L-ficolin, decreased expression level of HA, and/or decreased expression level of ST2 as compared to expression levels prior to defibrotide treatment.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-2, 4, 7, 18-20 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Akil et al (Biol Blood Marrow Transplant 2015 October; 21(10): 1739-1745) in view of Kypros et al (US 2012/0135427) and further in view of Richardson et al (Blood, 15 December 2002, Volume 100, Number 13: pages 43374343).
Akil et al discloses a method for the development of a biomarker panel for the diagnosis of sinusoidal obstructive syndrome (SOS) early after hematopoietic cell transplantation (HCT) (e.g. abstract, pgs 1, 5). Akil et al discloses obtaining plasma samples from a cohort of patients and measuring the levels of L-Ficolin, HA and ST2 (e.g pgs 3-5) by contacting the plasma with antibodies specific for the L-Ficolin, HA and ST2 and detecting the complexes to determine the level of the biomarkers (e.g. pgs 3-4). Akil et al discloses comparing the levels in the patients with SOS to that of a control without SOS and shows that ST2 and HA are elevated compared to the control and that L-Ficolin is decreased compared to that of a control (e.g. page 13, Fig. 1). Akil et al discloses that the high sensitivity and specificity of these biomarkers make them useful for real-time clinical testing and early clinical intervention using agents that target endothelial injury and have been proven to be effective for treating SOS (e.g. page 9). Akil et al discloses that the measurement of the biomarkers can be performed by ELISA (e.g. page 3). Akil et al discloses that the sample can be obtained the day of HCT (e.g. page 3). Akil et al discloses that the biomarkers had AUCs between 0.91 to 0.70) (e.g. page 5).
Akil et al differs from the instant invention in failing to explicitly teach performing the method on a subject (individual).
Kypros et al teaches that it is known and conventional in the art to apply methods toward an individual (subject) wherein the markers have been established in a cohort (e.g. para’s (e.g. para’s 0011-0017. 0021 and 0066-0070, 0086, Figures 1-2 and example 1).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the detection of the markers in an individual subject and compare to a control such as taught by Kypros et al into the method of Akil et al because Kypros et al shows that it is known and conventional in the art to apply the teachings of a cohort to that of an individual subjects. Thus, absent evidence to the contrary one of ordinary skill in the art would have a reasonable expectation of success incorporating the detection of the markers in an individual subject such as taught by Kypros et al into the method of Akil et al.
Akil et al and Kypros et al differ from the instant invention in failing to explicitly teach treating the subject at risk of SOS.
Richardson et al teaches that it is known and conventional in the art to treat a veno-occlusive disease (SOS) subject with defibrotide because defibrotide up-regulates the release of prostacyclin, prostaglandin E2, thrombomodulin and t-PA in vitro and in vivo and has been shown to decrease thrombin generation, tissue factor expression, PAI-1 release, and endothelin activity and has shown to be safe (e.g. pages 4337-4338). Richardson et al discloses administering the defibrotide for 15 days.
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate treatment such as taught by Richardson et al to the subject in the modified method of Akil et al because Akil et al specifically teaches that the high sensitivity and specificity of these biomarkers make them useful for real-time clinical testing and early clinical intervention using agents that target endothelial injury and have been proven to be effective for treating SOS and Richardson et al shows that it is known and conventional to treat a veno-occlusive disease (SOS) subject with defibrotide because defibrotide up-regulates the release of prostacyclin, prostaglandin E2, thrombomodulin and t-PA in vitro and in vivo and has been shown to decrease thrombin generation, tissue factor expression, PAI-1 release, and endothelin activity and has shown to be safe. Therefore, one of ordinary skill in the art would have a reasonable expectation of success incorporating treatment such as taught by Richardson et al to the subject in the modified method of Akil et al.
With respect to claim 20 as currently recited. The combination of Akil et al., Kypros et al and Richardson et al teach the same subjects and same therapeutic agents as currently recited and therefore it is deemed that the defibrotide results in increased expression levels of L-ficolin, decreased expression level of HA, and/or decreased expression level of ST2 as compared to expression levels prior to defibrotide treatment.
Claims 8-14 are rejected under 35 U.S.C. 103 as being unpatentable over Akil et al in view of Kypros et al and Richardson et al as applied to claims 1-2, 4, 7, 18-20 and 22-23 above, and further in view of Paczesny (US 2017/0248612).
See above for the teachings of Akil et al., Kypros et al and Richardson et al.
Akil et al., Kypros et al and Richardson et al differ from the instant invention in failing to teach the days the sample is obtained and also fails to teach the age of the subject.
Paczesny teaches that it is known and conventional in the art to obtain the blood sample in patients receiving HCT to measure HA, ST2 or L-ficolin at days 1-21 (e.g. para 0040). Paczesny also teaches that a subjects age for testing the sample can be ages 1-58 (e.g. page 6, Table 2).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate obtaining the same at any of days 1-21 and to include a subject at age 18 or less such as taught by Paczesny into the modified method of Akil et al because Paczesny et al shows that it is known and conventional. Further, the optimal day to obtain the sample and the optimum age of the subject can be determined by routine experimentation and thus would have been obvious to one of ordinary skill in the art. Further, It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation.” Application of Aller, 220 F.2d 454,456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation .” Id. At 458,105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Application of Boesch, 617 F.2d 272,276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Akil et al in view of Kypros et al and Richardson et al as applied to claims 1-2, 4, 7, 18-20 and 22-23 above, and further in view of Wang et al (Frontiers in Pharmacology, February 2021, Vol 12, Article 627126, pages 1-13).
See above for the teachings of Akil et al., Kypros et al and Richardson et al.
Akil et al., Kypros et al and Richardson et al differ from the instant invention in failing to teach the control is a healthy subject
Wang et al teaches that it is known and conventional in the art to use a healthy subject as a control in methods of diagnosing sinusoidal obstruction syndrome (e.g. abstract, pgs 1-2 and 5).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a healthy subject as the control in the modified method of Akil et al because Wang et al shows that it is known and conventional in the art. Therefore, one of ordinary skill in the art would have a reasonable expectation of success incorporating a healthy subject such as taught by Wang et al into the modified method of Ail et al.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Akil et al in view of Kypros et al and Richardson et al as applied to claims 1-2, 4, 7, 18-20 and 22-23 above, and further in view of Blankenberg et al (US 2006/0105419).
See above for the teachings of Akil et al., Kypros et al and Richardson et al.
Akil et al., Kypros et al and Richardson et al differ from the instant invention in failing to teach establishing threshold of 1100 ng/ml for L-ficolin, 200 ng/ml for HA and 45 ng/ml for ST2.
However, it was recognized in the prior art that the sensitivity and specificity is a measure of the accuracy of a test, reflecting the number (if any) of false positives and false negatives. Furthermore, sensitivity and specificity may be adjusted by adjusting the value of a threshold or cutoff value, above which (or below which, depending on how a marker changes with the disease/condition) the test is considered to be indicative of one state or condition (e.g., diseased/condition) and below which the test is considered to be indicative of another state or condition (e.g., non-diseased). See Blankenberg et al at [0007], [0028], [0084]. Accuracy need not be 100%; however Blankenberg et al indicates that particularly preferred would be where both the sensitivity and specificity are at least about 75%, more preferably at least about 80%, even more preferably at least about 85%, still more preferably at least about 90%, and most preferably at least about 95% [0028].
The teachings of Blankenberg et al indicate that the sensitivity and selectivity of a diagnostic test was known to be a result-effective variable, impacting the number of individuals who are correctly diagnosed with disease/condition. Furthermore, the teachings of Blankenberg et al indicate that it was known in the prior art to optimize tests for desired levels of sensitivity and specificity, by selecting appropriate threshold or cutoff values. Finally, Blankenberg et al clearly expresses that tests where both the sensitivity and specificity are at least about 80% would be viewed as particularly preferred.
Therefore, it would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate comparison of the levels and to arrive at the claimed invention by optimizing cutoff levels in order to achieve a desired sensitivity and specificity, given that such percentages were recognized in the art to be particularly preferred for diagnostic tests. One skilled in the art would have been motivated to select such threshold levels for sensitivity and specificity out of the course of routine optimization, given that these measures of test accuracy were recognized in the prior art to be result-effective variables that impact the number of false negatives and false positives for the test. Finally, one skilled in the art would have had a reasonable expectation of success in arriving at the claimed threshold for sensitivity and specificity since means of achieving desired sensitivity and specificity were known, namely by selecting an appropriate threshold or cutoff level (as taught by Blankenberg et al). It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation.” Application of Aller, 220 F.2d 454,456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation .” Id. At 458,105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Application of Boesch, 617 F.2d 272,276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Paczesny in view of Blankenberg et al (US 2006/0105419).
See above for the teachings of Paczesny.
Paczesny differs from the instant invention in failing to teach establishing threshold of 1100 ng/ml for L-ficolin, 200 ng/ml for HA and 45 ng/ml for ST2
However, it was recognized in the prior art that the sensitivity and specificity is a measure of the accuracy of a test, reflecting the number (if any) of false positives and false negatives. Furthermore, sensitivity and specificity may be adjusted by adjusting the value of a threshold or cutoff value, above which (or below which, depending on how a marker changes with the disease/condition) the test is considered to be indicative of one state or condition (e.g., diseased/condition) and below which the test is considered to be indicative of another state or condition (e.g., non-diseased). See Blankenberg et al at [0007], [0028], [0084]. Accuracy need not be 100%; however Blankenberg et al indicates that particularly preferred would be where both the sensitivity and specificity are at least about 75%, more preferably at least about 80%, even more preferably at least about 85%, still more preferably at least about 90%, and most preferably at least about 95% [0028].
The teachings of Blankenberg et al indicate that the sensitivity and selectivity of a diagnostic test was known to be a result-effective variable, impacting the number of individuals who are correctly diagnosed with disease/condition. Furthermore, the teachings of Blankenberg et al indicate that it was known in the prior art to optimize tests for desired levels of sensitivity and specificity, by selecting appropriate threshold or cutoff values. Finally, Blankenberg et al clearly expresses that tests where both the sensitivity and specificity are at least about 80% would be viewed as particularly preferred.
Therefore, it would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate comparison of the levels and to arrive at the claimed invention by optimizing cutoff levels in order to achieve a desired sensitivity and specificity, given that such percentages were recognized in the art to be particularly preferred for diagnostic tests. One skilled in the art would have been motivated to select such threshold levels for sensitivity and specificity out of the course of routine optimization, given that these measures of test accuracy were recognized in the prior art to be result-effective variables that impact the number of false negatives and false positives for the test. Finally, one skilled in the art would have had a reasonable expectation of success in arriving at the claimed threshold for sensitivity and specificity since means of achieving desired sensitivity and specificity were known, namely by selecting an appropriate threshold or cutoff level (as taught by Blankenberg et al). It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation.” Application of Aller, 220 F.2d 454,456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation .” Id. At 458,105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Application of Boesch, 617 F.2d 272,276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Akil et al in view of Kypros et al and Richardson et al as applied to claims 1-2, 4, 7, 18-20 and 22-23 above, and further in view of Diamandis et al (Immunoassay, Chapter 11, The Avidin-Biotin System, pages 237-267, 1996).
See above for the teachings of Akil et al., Kypros et al and Richardson et al.
Akil et al., Kypros et al and Richardson et al differ from the instant invention in failing to teach using detectable moieties that distinctly bind the antibodies.
Diamandis et al teaches the use of avidin-biotin system in immunoassay methods (method using specific binding agents). Diamandis et al disclose that antibody can be conjugated with biotin (first member of specific binding pair) and avidin (second member which binds to the first member) conjugated with a probe (p. 256-258, Figs 11.6-11.7). Diamandis et al discloses that streptavidin can be substituted for avidin (p. 248). Diamandis et al disclose that the avidin biotin system greatly improves the performance of the immunoassay system by substantial amplification of the signal and consequent sensitivity of the assay (p. 237 & 256-258).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate biotin with the antibodies of Akil et al in the modified method of Akil et al and avidin probes such as taught by Diamandis et al into the modified method of Akil et al for the detection of the L-ficolin, HA and ST2 because Diamandis et al teaches that the avidin biotin system greatly improves the performance of the immunoassay system by substantial amplification of the signal and consequent sensitivity of the assay. Therefore, one of ordinary skill in the art would have a reasonable expectation of success incorporating biotin with the antibodies of Akil et al in the modified method of Akil et al and avidin probes such as taught by Diamandis et al into the modified method of Akil et al for the detection of the L-ficolin, HA and ST2.
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 1-2, 4, 7-14, 20 and 22-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,193,945. Although the claims at issue are not identical, they are not patentably distinct from each other because methods of measuring HA, ST2 and L-Ficolin in a biological sample from a subject receiving HCT and also for treating SOS in the subject comprising contacting a sample with specific binding agents to form complexes and detecting the complexes to determine the biomarkers and one of skill in the art would recognize that the more comprehensive claims of 11,193,945 requiring at least 3 biomarkers would encompass the current application wherein only one of the biomarkers is required for the diagnosis.
Claim 29 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,193,945 in view of Diamandis et al (Immunoassay, Chapter 11, The Avidin-Biotin System, pages 237-267, 1996). Both the instant application and U.S. 11,193,945 involve measuring L-ficolin, HA and ST2 comprising obtaining a sample from a subject having received a hematopoietic stem cell transplantation and contacting the sample with antibodies and detecting the complexes. U.S. 11,193,945 does not specifically recite using detectable moieties that distinctly bind the antibodies. Diamandis et al teaches the use of avidin-biotin system in immunoassay methods (method using specific binding agents). Diamandis et al disclose that antibody can be conjugated with biotin (first member of specific binding pair) and avidin (second member which binds to the first member) conjugated with a probe (p. 256-258, Figs 11.6-11.7). Diamandis et al discloses that streptavidin can be substituted for avidin (p. 248). Diamandis et al disclose that the avidin biotin system greatly improves the performance of the immunoassay system by substantial amplification of the signal and consequent sensitivity of the assay (p. 237 & 256-258). Therefore, It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate biotin with the antibodies of U.S. 11,193,945 and avidin probes such as taught by Diamandis et al into the method of U.S. 11,193,945 for the detection of the L-ficolin, HA and ST2 because Diamandis et al teaches that the avidin biotin system greatly improves the performance of the immunoassay system by substantial amplification of the signal and consequent sensitivity of the assay.
Conclusion
No claims are allowed.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678
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