DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-11, 13, 14, 16-18, 20-22, 24, 26-29, 31 and 32 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on February 17, 2025 is acknowledged. Applicant’s election without traverse of the species, step (i), intraperitoneal, dexamethasone and FcγRIIB in the reply filed on February 17, 2025 is acknowledged. Claims 13, 14, 16-18, 20-22, 24, 26-29, 31 and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 5-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (ii).
Claims 1-4 and 8-11 are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 10, 1st paragraph). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 1-4 and 8-11 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The claims recite “judicial exceptions” as a limiting element or step without reciting additional elements/steps that integrate the judicial exceptions into the claimed inventions such that the judicial exceptions are practically applied, and are sufficient to ensure that the claims amount to significantly more than the judicial exceptions themselves. In the instant case, the “judicial exceptions ”predicting if a prophylactic or therapeutic treatment, an altered administration route and/or a modification of the therapeutic antibody molecule can prevent or mitigate a tolerability issue associated with intravenous administration to a human of a therapeutic antibody molecule binding specifically to a human target” and “observation of the mouse during a period following immediately after the administration of the therapeutic or surrogate antibody, wherein a decreased display of the macroscopic symptoms compared to the macroscopic symptoms displayed by the mouse in (i) or no display of the macroscopic symptoms during the period is an indication that pre-treatment with the prophylactic or therapeutic agent in combination with administration of the therapeutic antibody molecule to a human can prevent or mitigate the tolerability issue that otherwise would be associated with intravenous administration of the therapeutic antibody molecule to a human” which are not eligible for patent protection without significantly more recited in the claims.
A claim that focuses on use of judicial exceptions must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The PTO’s revised guidance on the application of § 101. (USPTO's January 7, 2019, Memorandum, 2019 Revised Patent Subject Matter Eligibility Guidance indicates that we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract
ideas (i.e., mathematical concepts, certain methods of organizing
human activity such as a fundamental economic practice, or mental
processes); and
(2) additional elements that integrate the judicial exception into a
practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that
exception into a practical application, do we then look to whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not
"well-understood, routine, conventional" in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities
previously known to the industry, specified at a high level of generality, to the judicial exception.
The present claims are directed to judicial exceptions? The claims recite judicial exceptions as limiting elements, the abstract ideas being ”predicting if a prophylactic or therapeutic treatment, an altered administration route and/or a modification of the therapeutic antibody molecule can prevent or mitigate a tolerability issue associated with intravenous administration to a human of a therapeutic antibody molecule binding specifically to a human target” and “observation of the mouse during a period following immediately after the administration of the therapeutic or surrogate antibody, wherein a decreased display of the macroscopic symptoms compared to the macroscopic symptoms displayed by the mouse in (i) or no display of the macroscopic symptoms during the period is an indication that pre-treatment with the prophylactic or therapeutic agent in combination with administration of the therapeutic antibody molecule to a human can prevent or mitigate the tolerability issue that otherwise would be associated with intravenous administration of the therapeutic antibody molecule to a human”. These limitations could be done by merely reviewing the data mentally and mentally predicting and observing. In the present claims there are no active method steps that transform the process into a practical application of the observing and predicting steps. Although claims 5-9 recite steps that could be used to mitigate the effect of the tolerability issues, the claims have been interpreted as being drawn to methods for predicting whether the mitigating steps would be necessary. In addition, the mitigation steps would only be carried out if there is an observation that the mitigating steps would be necessary. Thus, the claims do not require that any treatment to counteract the macroscopic symptoms will be administered, an altered form of administration will be used or a modified format of the therapeutic antibody will be used.
The next step is to determine whether the claim as a whole adds a specific limitation beyond the judicial exception that is not "well-understood, routine, conventional" in the field. The active method steps of “intravenous or intraperitoneal administration of the therapeutic antibody molecule, if cross-reactive with murine target to a mouse” set forth well-understood, routine and conventional activity engaged in by scientists at the time the application was filed and are the activities that a scientist would have relied upon to achieve the goals of the invention. Zuberi and Lutz (ILAR Journal 57:178-185, 2016, IDS) disclose using mouse models for predicting the therapeutic potential and adverse drug reactions to cancer treatments including antibody treatments (pages 182-184). Denayer et al (New Horizons in Translational Medicine 2:5-11, 2014) disclose assessing the efficacy and safety of drug treatments in mouse animal models for cancer treatment (Sections 5-6, pages 7-9). Jiskoot et al (J Pharm Sci 105:1567-1575, 2016, IDS) disclose using mouse models to examine the treatment regimen and development of unwanted immune responses to predict the therapeutic potential of intraperitoneal and intravenous administration of protein therapeutics (Abstract; pages 9-10).
In addition, the art discloses the pre-administration of corticosteroids and modified antibodies to prevent the adverse effects of was known in the art (Brownstein et al, WO 2020/047389, published March 5, 2020, IDS; Rangwala et al, WO 2020/037024, published February 20, 2020, IDS; Margiotta, J Clin Oncol, 36.15 suppl 2018, IDS). The art further discloses adverse effect of therapeutic drugs in mouse models (European Commission: "Animal Models in disease Studies and the development of new drugs", January 2013, IDS).
In sum, when the relevant factors are analyzed, they weigh against the present claims amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
Claim Rejections - 35 USC § 112
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.
Claims 1, 2 and 4 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 recites the limitation “comprising the following step(s) in addition to (i) as set out above”. It is not clear if the phrase contemplates the combination of section (i) with sections (ii)-(iv) or only the second paragraph of section (i). It has been interpreted as associated with the second paragraph of section (i). It is noted that Applicant elected section (i) in the restriction requirement of January 15, 2026
Claim 2 recites the limitation “(i) where after the state of the mouse is restored to the normal state further strengthens the indication that the intravenous administration of the therapeutic antibody molecule to the human will be associated with a tolerability issue”. However, there is nothing in claim 1, the claim for which claim 2 depends, reciting a method that may result in the restoration of the mouse to the normal state.
Claim 4 recites “ a method according to claim 1, wherein at least one of the following additional parameters, decreased blood pressure, decreased platelet count, and or increased liver enzymes (AST/ALT) observed during the period in (i) further strengthens the indication that the intravenous administration of the therapeutic antibody molecule to a human will be associated with a tolerability issue. However, claim 1 does not include the term “parameters”. There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 4, 8 and 9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 recites a method according to claim 1, wherein a display m (i) of 1-3 additional macroscopic symptoms selected from impaired balance, piloerection, and hunching followed by un-natural body posture during the period. Claim 4 recites a method according to claim 1, wherein at least one of the following additional parameters”.
Claims 8 and 9 are objected to because of the following informalities: Claim 8 recites “a method for predicting if an altered administration route can prevent or mitigate a tolerability issue” while depending on claim 1. However, claim 1 also recites “an altered administration route”. In addition, claim 9 recites “ a method for predicting if a modification of the therapeutic antibody molecule can prevent or mitigate a tolerability issue” while depending on claim 1. However, claim 1 recites “a modification of the therapeutic antibody molecule can prevent or mitigate a tolerability issue”.
Thus, the claims comprise additional steps and do not further limit the subject matter of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Zuberi and Lutz (ILAR Journal 57:178-185, 2016, IDS, cited previously) Denayer et al (New Horizons in Translational Medicine 2:5-11, 2014, cited previously) Jiskoot et al (J Pharm Sci 105:1567-1575, 2016, IDS, cited previously), in view of European Commission: ("Animal Models in disease Studies and the development of new drugs", January 2013, IDS).
Claim 1 is drawn to a method for predicting if a therapeutic antibody molecule binding specifically to a human target will be associated with a tolerability issue in connection with intravenous administration to a human, comprising the following step:
intravenous or intraperitoneal administration of the therapeutic antibody molecule, if cross-reactive with murine target, or a surrogate antibody, to a mouse and observation of the mouse during a period following immediately after the administration of the therapeutic or surrogate antibody, wherein a display of the macroscopic symptoms isolation and decreased activity during the period followed by restoration of the state of the mouse to the normal state is an indication that the intravenous administration of the therapeutic antibody molecule to a human will be associated with a tolerability issue.
It is noted that the and/or connector in (i) indicates that the second paragraph is not required for rejections under 35 USC 103.
Zuberi disclose using mouse models for predicting the therapeutic potential and adverse drug reactions to cancer treatments including antibody treatments (pages 182-184). Zuberi disclose that several attributes make the mouse an excellent model organism for biomedical research (page 179, 2nd column). Zuberi disclose that the mouse is an excellent tool to generate and study animal models of human disease (Id). Zuberi disclose that mice are susceptible to the same monogenic and polygenic diseases found in humans. Zuberi disclose that the recent development of the Collaborative Cross and Diversity Outbred mice which provides new tools capable of replicating genetic diversity to that approaching the diversity found in human populations (Abstract; pages 182). Zuberi disclose that the Collaborative Cross and Diversity Outbred strains thus provide a means to observe and characterize toxicity or efficacy of new therapeutic drugs for a given population (Id).
Denayer et al disclose assessing the efficacy and safety of drug treatments in mouse animal models for cancer treatment (Sections 5-6, pages 7-9). Denayer disclose the creation of humanized mouse models for preclinical cancer research with drug candidates (section 5, pages 7-8).
Jiskoot et disclose using mouse models to examine the treatment regimen and development of unwanted immune responses to predict the therapeutic potential of intraperitoneal and intravenous administration of protein therapeutics (Abstract; pages 9-10).
Thus, Zuberi, Denayer and Jiskoot all disclose the use of mouse animal models to predict the efficacy and safety of antibody treatment regimens for cancer treatment in humans. Antibody treatments for cancer patients would be intravenous while Jiskoot disclose that intraperitoneal or intravenous administration of the therapeutics in mouse models. Both Zuberi and Denayer disclose enhanced mouse models that may be used to more accurately predict the clinical efficacy of cancer treatments in humans.
While Zuberi, Denayer and Jiskoot disclose measuring the adverse effects of antibody treatment regimens, they do not disclose the specific macroscopic symptoms associated with testing antibody therapeutic regimens in mice.
However, the European Commission discloses the macroscopic symptoms seen in mice upon the treatment of mice with therapeutic drugs such as weight loss, lethargy, aggression, mobility problems (pages 10-12, 35).
One of ordinary skill in the art would have been motivated to apply the European Commission’s list of adverse macroscopic symptoms for mice treated with therapeutic regimens to Zuberi, Denayer and Jiskoot disclosure for the use of mouse animal models to predict the efficacy and safety of antibody treatment regimens for cancer because the European Commission, Zuberi, Denayer and Jiskoot all concern the use of animal models to assess the safety and efficacy of therapeutic regimens in mouse models. European Commission, Zuberi, Denayer and Jiskoot all contemplate the use of mouse models to predict the safety and efficacy of therapeutic cancer regiments in humans. It would have been obvious to combine the Zuberi, Denayer and Jiskoot disclosure for the use of mouse animal models to predict the efficacy and safety of antibody treatment regimens for cancer with the European Commission’s list of adverse macroscopic symptoms for mice treated with therapeutic regimens to have a method for predicting if a therapeutic antibody molecule binding specifically to a human target will be associated with a tolerability issue in connection with intravenous administration to a human, comprising the intraperitoneal administration of the therapeutic antibody molecule to a mouse and observation of the mouse during a period following immediately after the administration of the antibody. Given that Jiskoot et disclose using mouse models to examine the treatment regimen and development of unwanted immune responses to predict the therapeutic potential of intraperitoneal and intravenous administration it would have been obvious to assess the route of administration in examining the safety and efficacy of the treatment regimen.
Claims 1-3 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Zuberi and Lutz (ILAR Journal 57:178-185, 2016, IDS, cited previously) Denayer et al (New Horizons in Translational Medicine 2:5-11, 2014, cited previously) Jiskoot et al (J Pharm Sci 105:1567-1575, 2016, IDS, cited previously), in view of European Commission: ("Animal Models in disease Studies and the development of new drugs", January 2013, IDS) in further view of Tutt et al (J Immunol 195:5503-5516, 2015, IDS), Roghanian et al (Cancer Cell 27:473-488, 2015, IDS).
Zuberi, Denayer, Jiskoot and the European Commission have been described supra.
Neither Zuberi, Denayer, Jiskoot nor the European Commission disclose that the therapeutic antibody molecule is a human anti-FcyRIIB antibody.
Tutt disclose human and mouse anti-FcyRIIB antibodies that bind mouse and human FcyRIIB (Table I). Tutt disclose that the monoclonal antibodies AT10, KB6.1 and IV.3 bind both hFcγRIIA and -B (page 5504, 1st column 2nd paragraph). Tutt disclose that most anti-FcγR antibodies bind more than one FcγR (page 5504, 2nd column; Table II). Tutt disclose IgG1 and IgG2a anti-FcyRIIB antibodies (Id). Tutt disclose that the FcγRs are key determinants of mAb immunotherapy (Abstract, page 5503, 2nd column). Tutt disclose that it is clear that reagents capable of precisely/specifically staining and manipulating the individual FcγRs are critical to further dissect the key mechanisms of action of therapeutic mAbs and to better define the central effector cells and FcgR involved in both induced and ongoing immune responses in normal and pathological settings (page 5504, 1st column 1st paragraph). Tutt discloses that the consequences of FcγR engagement vary from phagocytosis and cytotoxic granule release to cytokine production and release of inflammatory mediators (page 5503, 2nd column).
Roghanian disclose human IgG1 anti-FcyRIIB antibodies having an IgG1 (page 479, 1st paragraph). Roghanian disclose modified anti- FcyRIIB antibodies that cannon bind FcγR through their Fc domain. Roghanian disclose evidence of mouse anti-human antibody responses (page 479, 1st column). Roghanian disclose that the human anti- FcyRIIB antibodies have intrinsic activity (page 479, 2nd column to page 481, 1st column).
One of ordinary skill in the art would have been motivated to apply Tutt and Roghanian’s human IgG1 anti-FcyRIIB antibodies to Zuberi, Denayer, Jiskoot and the European Commission’s method for predicting if a therapeutic antibody molecule binding specifically to a human target will be associated with a tolerability issue in connection with intravenous administration to a human, comprising the intraperitoneal administration of the therapeutic antibody molecule to a mouse and observation of the mouse because Tutt disclose that FcγR engagement induce cytokine production and release of inflammatory mediators. It would have been prima facie obvious to substitute Tutt and Roghanian’s human IgG1 anti-FcyRIIB antibodies for Zuberi, Denayer, Jiskoot’s generic clinical antibody to have a method for predicting if anti-FcyRIIB antibody binding specifically to a human target will be associated with a tolerability issue in connection with intravenous administration to a human, comprising the intraperitoneal administration of the anti-FcyRIIB antibodies to a mouse and observation of the mouse during a period following immediately after the administration of the anti-FcyRIIB antibodies. One of ordinary skill in the art would have had a reasonable expectation of success because the use of animal models to predict the safety and efficacy of therapeutic drugs was well known as well as the administration of an anti-FcyRIIB antibodies for therapeutic purposes.
Claims 1-4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Zuberi and Lutz (ILAR Journal 57:178-185, 2016, IDS, cited previously) Denayer et al (New Horizons in Translational Medicine 2:5-11, 2014, cited previously) Jiskoot et al (J Pharm Sci 105:1567-1575, 2016, IDS, cited previously), in view of European Commission: ("Animal Models in disease Studies and the development of new drugs", January 2013, IDS, cited previously) in further view of McDevitt et al (US 11,591,395, published February 11, 2021, filed April 17, 2020) and Hamilton et al (US 2023/0181593, published June 15, 2023, effective filing date May 21, 2020).
Zuberi, Denayer, Jiskoot and the European Commission have been described supra.
Neither Zuberi, Denayer, Jiskoot nor the European Commission disclose an additional parameter from decreased blood pressure, decreased platelet count, and or increased liver enzymes.
McDevitt disclose that an adverse event from treatment with an anti-PSMAxCD3 bispecific antibody was adverse vital signs (heart rate, systolic and diastolic blood pressure) (column 11, lines 41-57).
Hamilton disclose that drug-induced toxicity included liver toxicity (paragraph 102).
One of ordinary skill in the art would have been motivated to apply McDevitt and Hamilton measures of adverse events from antibody treatment to Zuberi, Denayer, Jiskoot and the European Commission’s method for predicting if a therapeutic antibody molecule binding specifically to a human target will be associated with a tolerability issue in connection with intravenous administration to a human, comprising the intraperitoneal administration of the therapeutic antibody molecule to a mouse and observation of the mouse because McDevitt, Hamilton, and the European Commission all disclose parameters indicative of adverse reactions from antibody therapy. It would have been prima obvious to combine Zuberi, Denayer, Jiskoot and the European Commission’s method for predicting if a therapeutic antibody molecule binding specifically to a human target will be associated with a tolerability issue with McDevitt and Hamilton measures of adverse events from antibody treatment to have a have a method for predicting if antibody binding specifically to a human target will be associated with a tolerability issue in connection with intravenous administration to a human, comprising the intraperitoneal administration of the antibodies to a mouse and observation of the mouse during a period following immediately after the administration of the antibodies, wherein the observed parameter include the macroscopic symptoms, isolation, decreased activity, decreased blood pressure and increased liver enzymes.
Summary
No claims allowed.
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/MARK HALVORSON/ Primary Examiner, Art Unit 1646
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