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 .
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 107, 110-112, and 115 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon and an abstract idea without significantly more.
The claim 107 recites a method for determining whether a patient is suffering from Alzheimer’s disease (AD). The claim requires four steps: measuring the level of at least one inflammasome protein, ASC, in a biological sample; comparing the level of ASC with a reference value or range; selecting the patient as having AD when the patient has an expression level of ASC between 264.9 pg/ml and 560 pg/ml; and administering an anti-ASC antibody.
The claim recites a natural phenomenon or the correlation between the expression of at least one inflammasome protein, ASC, and the presence of AD. Additionally, the steps of comparing the level of expression to a reference range or value and selecting a patient as having disease when the patient has an expression level of ASC between 264.9 pg/ml and 560 pg/ml can be completed entirely in the mind and are mental processes.
This judicial exception is not integrated into a practical application because the additional elements in the claim: the step of measuring the expression level of at least one inflammasome protein in a biological sample is merely an extra-solution activity and the step of administering occurs regardless of the inflammasome protein or ASC expression level.
These elements do not apply, rely on or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. According to 2019 PEG, limitations that are indicative of integration into a practical application when recited in a claim with a judicial exception include:
Improvements to the functioning of a computer, or to any other technology or technical field, as discussed in MPEP 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for disease or medical condition – see Vanda Memo
Applying the judicial exception with, or by use of, a particular machine, as discussed in MPEP 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP 2106.05(e) and the Vanda Memo issued in June 2018.
Limitations that are not indicative of integration into a practical application when recited in a claim with a judicial exception include:
Adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, or merely uses a computer as a tool to perform an abstract idea, as discussed in MPEP 2106.05(f);
Adding insignificant extra-solution activity to the judicial exception, as discussed in MPEP 2106.05(g); and
Generally linking the use of the judicial exception to a particular technological environment or field of use, as discussed in MPEP 2106.05(h).
The claims fail to meet step 2B because the additional elements were well known and conventional in the art. For example, Grinstein et al. (Clinical Immunology. 191: 100-109; Published: November 26, 2017) teaches measuring the expression of NLRP3, NLRC4, and AIM2 inflammasome components in blood, Riteau et al. (Editors: Di Virgilio and Pelegrin. NLR Proteins: Methods and Protocols, Methods in Molecular Biology, Vol. 1417: Chapter 3.; Published: May 25, 2016) teaches methods for measuring IL-1β and IL-18 in ex vivo tissue samples and biological fluids, and Ulke-Lemée et al. (Inflammation. 41(4): 1396-1408; Published: August 2018) teaches measuring ASC in urine samples. Therefore, the additional steps/elements do not add significantly more to the judicial exception.
Since the claims as a whole do not include additional elements that are sufficient to amount to significantly more than the judicial exception, the claims are not directed to eligible subject matter under 35 U.S.C 101.
Examiner suggests the following amendments to overcome this rejection 1. Delete the step of “selecting”; and 2. Revise the step of “comparing” as follows:
“comparing the expression level of ASC in the biological sample to a pre-determined reference value, range of reference values for ASC, or against a healthy individual not exhibiting symptoms of AD as a control, wherein the expression level of ASC is between 264.9 pg/ml and 560 pg/ml; and”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 107, 110-112, 115, and 116 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 107 recites the limitation "the subject" in line 15. There is insufficient antecedent basis for this limitation in the claim. For the purpose of compact prosecution, “the subject” is interpreted as referring to the patient. Claims 110-112, 115, and 116 are rejected for depending from claim 107 and failing to remedy the indefiniteness.
Claim Rejections - 35 USC § 112(d)
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 112 is 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 107 recites that the control is a healthy individual not exhibiting symptoms of AD. Claim 112, which depends from claim 107, also recites the control is a healthy individual not clinical exhibiting symptoms of AD. Claim 112 fails to further limit.
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 § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 107, 110-112, 115, and 116 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.
Claim 107, from which all other claims depend, recites a step of administering an “antibody or antibody fragment thereof that binds specifically to ASC” and encompasses antibodies comprising a VH region having at least 95% identity to SEQ ID NOs: 18, 19, 20, 21, or 22 and a VL region having at least 95% identity to SEQ ID NOs: 28, 29, 30, or 31. Thus, the claim recites administering a genus of proteins which perform a particular function (binding specifically to ASC) and can vary by up to 5% identity in each anywhere in the VH and VL.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites.
Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (PNAS. 79: 1979-1983; Published: March 15, 1982). Rudikoff et al. teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Similarly, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Murphy et al. (Journal of Immunological Methods. 463: 127-133; Published: October 12, 2018), teach that altering amino acid D92 in the complementarity determining region light chain region 3 (CDRL3) of single chain fragment variable (scFv) 2G1 obliterates its capacity to bind to microcystinleucine-arginine (MC-LR) and changing phenylalanine at position 91 to tyrosine caused an increased in binding to MC-LR, compared to the parent clone; see page 130, Section 3.2, paragraph 2 and page 131, column 1, paragraph 2. The alterations in binding that were observed in these two variants demonstrate the highly influential role of CDRL3 in binding MC-LR.
Thus, particularly in regards to the CDR sequences, it is unpredictable how these sequences of the antibody can be altered and still retain the recited function of binding ASC.
Indeed, the anti-ASC antibody to be administered in claim 107 encompasses alterations anywhere in the VH and VL, including to the CDRs, resulting in up to 5% variability in each the VH and VL. The number of potential variant antibodies with up to 5% sequence variability in each the VH and VL is extensive with, presumably, only a portion of those variants retaining the ASC binding function recited in claim 107.
In contrast, the instant disclosure teaches only the variants comprising a VH of SEQ ID NOs: 18-22 and a VL of SEQ ID NOs: 28-31 with all variants taught having the CDRs of SEQ ID NOs: 6, 7, 8, 12, 13, and 14. While the Specification does state the antibody having at least 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NOs: 18-22 and 28-31, there is no specific teaching regarding where in the VH and VL this 5% variability can occur and still yield an antibody which will bind ASC. Similarly, the Specification states that the antibody may comprise one amino acid substitution in each CDR, but fails to provide any specific guidance regarding which CDR residues may be more critical to retain binding specificity or which amino acid substitutions may still yield an antibody which binds ASC. Again, the disclosure only reduces to practice antibodies having VH and VL sequences of SEQ ID NOs: 18-22 and 28-31, which differ from each other by up to 5%, but all retain the same set of six CDRs.
Based on the lack of predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of proteins which bind specifically to ASC and can vary by up to 5% identity in each anywhere in the VH and VL based on disclosure of five VHs and four VLs all which retain the same set of six CDRs.
Examiner suggests amending claim 107 such that the anti-ASC antibody comprises the set of six CDRs of SEQ ID NOs: 6, 7, 8, 12, 13, and 14. The claim may continue to recite variants having up to 5% variability in each the VH (i.e. SEQ ID NOs: 18-22) and VL (i.e. SEQ ID NOs: 28-31) so long as those variants are constrained to comprising the set of six CDRs of SEQ ID NOs: 6, 7, 8, 12, 13, and 14.
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.
Claims 107-112, and 115-117 are rejected under 35 U.S.C. 103 as being unpatentable over Vaccari et al. (WO 2019/060516 A1; Published: March 28, 2019) in view of Keane et al. (US 2019/0002550 A1; Published: January 3, 2019).
Regarding claims 107 and 112, Vaccari et al. teaches a method for evaluating a patient suspected of having a brain injury, including Alzheimer’s disease (AD), comprising measuring the level of at least one inflammasome protein, comparing the level to that of a healthy control not presenting with symptoms of brain injury or a reference value or range, wherein an enhanced or elevated level of one inflammasome protein, including ASC, indicates the patient should be selected as having brain injury, including Alzheimer’s disease (AD); see claims 84, 85, 88-94, 96, and 98 and pages 3 and 20. Additionally, Vaccari et al. teaches using the method in a patient presenting with symptoms of brain injury, including Alzheimer’s disease; see claim 85. Vaccari et al. teaches that the inflammasome protein may be ASC; see claim 89. Additionally, regarding claim 111, Vaccari et al. teaches that the inflammasome protein is measured by immunoassay utilizing one or more antibodies directed to the inflammasome protein; see claim 87. Regarding claim 110, Vaccari et al. teaches that method comprises measuring the level of an inflammasome protein in a serum biological sample; see claims 86 and 95. Regarding claim 115, Vaccari et al. teaches that the method can be optimized for each type of brain injury with minimum sensitivity and specificity varying by the cut-off level of ASC for each injury type; see claims 99-126.
Vaccari et al. does not teach administering the anti-ASC antibody recited in claim 107.
Keane et al. teaches anti-ASC antibodies comprising a VH of SEQ ID NOs: 18-22 or having at least 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NOs: 18-22 and a VL of SEQ ID NOs: 28-31 or having at least 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NOs: 28-31; see claims 2-7. These VH and VL sequences are 100% identical to the instant sequences using the same SEQ ID NO. Further, Keane et al. teaches a pharmaceutical composition comprising the anti-ASC antibody and administering the anti-ASC antibody to treat inflammasome-related inflammation, including central nervous system (CNS) injury, an autoimmune, or neurodegenerative disease; see claims 36-40. Keane et al. teaches that autoimmune or neurodegenerative diseases to be treated with the anti-ASC antibody includes Alzheimer’s disease; see paragraph 0010.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Vaccari et al. and Keane et al. using the method of diagnosing brain injury by measuring ASC in a biological sample and comparing that expression level to a reference value, range or control and treating with the anti-ASC antibody as taught by Keane et al. Since Vaccari et al. teaches that Alzheimer’s disease is a type of brain injury, it would have been obvious to one of ordinary skill in the art to use the method of diagnosing brain injury to diagnose Alzheimer’s disease. Further, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat Alzheimer’s disease once diagnosed and Keane et al. teaches treating inflammasome-related inflammation, including inflammation from Alzheimer’s disease, with an anti-ASC antibody comprising a VH of SEQ ID NO: 18-22 and VL of SEQ ID NOs: 28-31 or having at least 95% identity to the VH and VL sequences.
One of ordinary skill in the art, seeing the high degree of variability among patients diagnosed with MCI, a type of brain injury, and knowing that this data was obtained by a small sample size, only 32 patients, would have been motivated to expand the data set provided by Vaccari et al. to optimize, through routine experimentation, the cut-off values and relative sensitivity and specificity for ASC in Alzheimer’s disease. Further, one of ordinary skill in the art would have been motivated to create a similar cut-off or reference range for patients with AD through routine optimization since Vaccari et al. classifies both MCI and AD as brain injury and teaches that the method can be applied to both.
Further, regarding claims 107 and 116, 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).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
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 107, 110-112, 115, and 116 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 6 of U.S. Patent No. 10,703,811 B2 in view of Vaccari et al. (WO 2019/060516 A1; Published: March 28, 2019).
Issued claims 1-3 and 6 teach an anti-ASC antibody comprising a VH of SEQ ID NOs: 18-22 and a VL of SEQ ID NOs: 28-31, which are 100% identical to the instant sequences using the same SEQ ID NO, and a pharmaceutical composition comprising the anti-ASC antibody.
The issued claims do not teach a method comprising measuring ASC to diagnose Alzheimer’s disease.
Regarding claims 107 and 112, Vaccari et al. teaches a method for evaluating a patient suspected of having a brain injury, including Alzheimer’s disease (AD), comprising measuring the level of at least one inflammasome protein, comparing the level to that of a healthy control not presenting with symptoms of brain injury or a reference value or range, wherein an enhanced or elevated level of one inflammasome protein, including ASC, indicates the patient should be selected as having brain injury, including Alzheimer’s disease (AD); see claims 84, 85, 88-94, 96, and 98 and pages 3 and 20. Additionally, Vaccari et al. teaches using the method in a patient presenting with symptoms of brain injury, including Alzheimer’s disease; see claim 85. Vaccari et al. teaches that the inflammasome protein may be ASC; see claim 89. Additionally, regarding claim 111, Vaccari et al. teaches that the inflammasome protein is measured by immunoassay utilizing one or more antibodies directed to the inflammasome protein; see claim 87. Regarding claim 110, Vaccari et al. teaches that method comprises measuring the level of an inflammasome protein in a serum biological sample; see claims 86 and 95. Regarding claim 115, Vaccari et al. teaches that the method can be optimized for each type of brain injury with minimum sensitivity and specificity varying by the cut-off level of ASC for each injury type; see claims 99-126.
Since Vaccari et al. teaches that Alzheimer’s disease is a type of brain injury, it would have been obvious to one of ordinary skill in the art to use the method of diagnosing brain injury to diagnose Alzheimer’s disease. Further, it would have been obvious to treat Alzheimer’s disease once diagnosed. Accordingly, when the issued claims of U.S. Patent No. 10,703,811 B2 are properly construed using its accompanying specification, the claimed method comprising administering the anti-ASC antibody comprising a VH of SEQ ID NO: 18-22 and VL of SEQ ID NOs: 28-31 to treat Alzheimer’s disease is obvious over the claims to the pharmaceutical composition comprising the anti-ASC antibody, since this same utility for the anti-ASC antibody is disclosed in the specification of U.S. Patent No. 10,703,811 B2; see column 3 line 28. One would have had a reasonable expectation of success treating Alzheimer’s disease using with anti-ASC antibody because Vaccari et al. teaches that Alzheimer’s disease is associated with elevated inflammasome proteins and activation and that neuroprotective treatments for brain injury include antibodies directed against inflammasome proteins; see page 35.
One of ordinary skill in the art, seeing the high degree of variability among patients diagnosed with MCI, a type of brain injury, and knowing that this data was obtained by a small sample size, only 32 patients, would have been motivated to expand the data set provided by Vaccari et al. to optimize, through routine experimentation, the cut-off values and relative sensitivity and specificity for ASC in Alzheimer’s disease. Further, one of ordinary skill in the art would have been motivated to create a similar cut-off or reference range for patients with AD through routine optimization since Vaccari et al. classifies both MCI and AD as brain injury and teaches that the method can be applied to both.
Further, regarding claims 107 and 116, 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).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 107, 110-112, 115, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37-39, 46, 47, and 56 of copending Application No. 17/255,653 in view of Vaccari et al. (WO 2019/060516 A1; Published: March 28, 2019).
Copending claims 37-39, 46, 47, and 56 teach a method of treating inflammasome-related inflammation comprising administering an anti-ASC antibody comprising a VH of SEQ ID NOs: 18-22 and a VL of SEQ ID NOs: 28-31, which are 100% identical to the instant sequences using the same SEQ ID NO, and a pharmaceutical composition comprising the anti-ASC antibody.
The copending claims do not teach a method comprising measuring ASC to diagnose Alzheimer’s disease nor that Alzheimer’s disease is associated with inflammasome-related inflammation.
Regarding claims 107 and 112, Vaccari et al. teaches a method for evaluating a patient suspected of having a brain injury, including Alzheimer’s disease (AD), comprising measuring the level of at least one inflammasome protein, comparing the level to that of a healthy control not presenting with symptoms of brain injury or a reference value or range, wherein an enhanced or elevated level of one inflammasome protein, including ASC, indicates the patient should be selected as having brain injury, including Alzheimer’s disease (AD); see claims 84, 85, 88-94, 96, and 98 and pages 3 and 20. Additionally, Vaccari et al. teaches using the method in a patient presenting with symptoms of brain injury, including Alzheimer’s disease; see claim 85. Vaccari et al. teaches that the inflammasome protein may be ASC; see claim 89. Additionally, regarding claim 111, Vaccari et al. teaches that the inflammasome protein is measured by immunoassay utilizing one or more antibodies directed to the inflammasome protein; see claim 87. Regarding claim 110, Vaccari et al. teaches that method comprises measuring the level of an inflammasome protein in a serum biological sample; see claims 86 and 95. Regarding claim 115, Vaccari et al. teaches that the method can be optimized for each type of brain injury with minimum sensitivity and specificity varying by the cut-off level of ASC for each injury type; see claims 99-126.
Since Vaccari et al. teaches that Alzheimer’s disease is a type of brain injury which is associated with inflammasome-related inflammation, it would have been obvious to one of ordinary skill in the art to use the method of diagnosing brain injury to diagnose Alzheimer’s disease. Further, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to treat Alzheimer’s disease, which is associated with inflammasome-related inflammation, once diagnosed and since the copending claims teach a method of treating inflammasome-related inflammation comprising administering the anti-ASC antibody comprising a VH of SEQ ID NO: 18-22 and VL of SEQ ID NOs: 28-31, it would have been obvious to treat Alzheimer’s disease once diagnosed, with the method of the copending claims treating inflammasome-related inflammation.
One of ordinary skill in the art, seeing the high degree of variability among patients diagnosed with MCI, a type of brain injury, and knowing that this data was obtained by a small sample size, only 32 patients, would have been motivated to expand the data set provided by Vaccari et al. to optimize, through routine experimentation, the cut-off values and relative sensitivity and specificity for ASC in Alzheimer’s disease. Further, one of ordinary skill in the art would have been motivated to create a similar cut-off or reference range for patients with AD through routine optimization since Vaccari et al. classifies both MCI and AD as brain injury and teaches that the method can be applied to both.
Further, regarding claims 107 and 116, 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).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection.
Claims 107, 110-112, 115, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 20-22 of copending Application No. 19/074,167 in view of Vaccari et al. (WO 2019/060516 A1; Published: March 28, 2019).
Claims 107, 108, 110-112, 115, and 116 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 21-23 of copending Application No. 18/464,174 in view of Vaccari et al. (WO 2019/060516 A1; Published: March 28, 2019).
The following analysis applies to both rejections over the copending claims of Application Nos. 19/074,167 and 18/464,174.
Copending claims 1-13, 20, and 21 of Application No. 19/074,167 and copending claims 1-14, 21 and 22 of Application No. 18/464,174 teach a method of treating an inflammatory neurologic condition, including Alzheimer’s disease comprising administering an anti-ASC antibody comprising a VH of SEQ ID NOs: 18-22 and VL of SEQ ID NOs: 28-31 or having a VH and VL of at least 95% identity to SEQ ID NOs: 18-22 and 28-31. These sequences are 100% identical to the instant sequences of the same SEQ ID NO.
While copending claim 22 of Application No. 19/074,167 and copending claim 23 of Application No. 18/464,174 teaches a similar method of diagnosing Alzheimer’s disease where the level of ASC is measured, it differs slightly from that instantly claimed as the biological sample is limited to brain tissue and no comparison to a reference value, range, or control is made in the method of the copending claims.
Regarding claims 107 and 112, Vaccari et al. teaches a method for evaluating a patient suspected of having a brain injury, including Alzheimer’s disease (AD), comprising measuring the level of at least one inflammasome protein, comparing the level to that of a healthy control not presenting with symptoms of brain injury or a reference value or range, wherein an enhanced or elevated level of one inflammasome protein, including ASC, indicates the patient should be selected as having brain injury, including Alzheimer’s disease (AD); see claims 84, 85, 88-94, 96, and 98 and pages 3 and 20. Additionally, Vaccari et al. teaches using the method in a patient presenting with symptoms of brain injury, including Alzheimer’s disease; see claim 85. Vaccari et al. teaches that the inflammasome protein may be ASC; see claim 89. Additionally, regarding claim 111, Vaccari et al. teaches that the inflammasome protein is measured by immunoassay utilizing one or more antibodies directed to the inflammasome protein; see claim 87. Regarding claim 110, Vaccari et al. teaches that method comprises measuring the level of an inflammasome protein in a serum biological sample; see claims 86 and 95. Regarding claim 115, Vaccari et al. teaches that the method can be optimized for each type of brain injury with minimum sensitivity and specificity varying by the cut-off level of ASC for each injury type; see claims 99-126.
Since Vaccari et al. teaches that Alzheimer’s disease is a type of brain injury, it would have been obvious to one of ordinary skill in the art to use the method of diagnosing brain injury to diagnose Alzheimer’s disease. Further, it would have been obvious to treat Alzheimer’s disease once diagnosed. Since the method of the copending claims Application Nos. 19/074,167 and 18/464,174 teaches treating Alzheimer’s disease comprising administering the anti-ASC antibody comprising a VH of SEQ ID NO: 18-22 and VL of SEQ ID NOs: 28-31, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success to administer the anti-ASC antibody to the patient diagnosed with Alzheimer’s disease.
One of ordinary skill in the art, seeing the high degree of variability among patients diagnosed with MCI, a type of brain injury, and knowing that this data was obtained by a small sample size, only 32 patients, would have been motivated to expand the data set provided by Vaccari et al. to optimize, through routine experimentation, the cut-off values and relative sensitivity and specificity for ASC in Alzheimer’s disease. Further, one of ordinary skill in the art would have been motivated to create a similar cut-off or reference range for patients with AD through routine optimization since Vaccari et al. classifies both MCI and AD as brain injury and teaches that the method can be applied to both.
Further, regarding claims 107 and 116, 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).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s amendments filed October 23, 2025 are acknowledged. Any rejection not repeated above is resolved by amendment.
In response to Applicant’s amendments filed October 23, 2025, the rejection under 35 U.S.C. 103 has been amended substantially, but continues to rely on Vaccari et al. (WO 2019/060516 A1; Published: March 28, 2019).
Applicant asserts that Vaccari et al. relates only to measuring inflammasome protein for determining MS, stroke, traumatic brain injury, or mild cognitive impairment and does not provide an enabling disclosure for Alzheimer’s disease. Examiner disagrees. Vaccari et al. teaches the method of measuring inflammasome proteins, including ASC, to diagnose brain injury, which includes Alzheimer’s disease according to Vaccari et al.; see claims 84, 85, 88-94, 96, and 98 and pages 3 and 20. Applicant refers to the data presented in instant Figures 21A-21D, 23B, and 25A which demonstrate differing ROC, relating to the sensitivity or specificity, in MCI versus AD. Indeed, one would expect that each disease would require optimization of the cut off values or reference values, which would impact sensitivity and specificity. Reviewing the various cut-off values and ROC data from the examples presented in the Specification of Vaccari et al. where samples from patients having each type of brain injury (i.e. MS, stroke, TBI, and MCI) are analyzed, one of ordinary skill in the art would recognize that such data need be optimized for Alzheimer’s disease. While such optimization is well within the means of one of ordinary skill in the art, the Examples in Vaccari et al. would enable one to follow to the same biomarker analysis to arrive at optimized values as in instant claims 107 and 116.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Liao et al. (Investigative Ophthalmology & Visual Science. 60(8): 3034–3045; Published: July 2019) teaches that retinal cell death is associated with NLRP3 inflammasome activation.
Liu et al. (Investigative Ophthalmology & Visual Science. 54(3): 2225-2237; Published: March 9, 2014) teaches that amyloid-β is associated with inflammasome activation in the retina.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1646
/JULIET C SWITZER/Primary Examiner, Art Unit 1682