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 .
1. Claims 1-3, 5, 8-20, 31, 32 and 35-52 are pending in the instant patent application.
Claims 1-3, 5, 8-20, 31, 32 and 35-52 are under examination.
Claim Objections
2. Claims 8, 19, 20, 44 and 52 are objected to because of the following informalities:
The claims recite acronyms, see “BCR,” “TCR” and “HLA,” for example, without first providing the full name of the terms. It is suggested that the terms be spelled out at their first use and in all independent claims so that it is clearly understood what they stand for. Appropriate correction is suggested.
3. Applicant is advised that should claims 16 and 17 be found allowable, claims 47 and 49, respectively, will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Briefly, claims 16 and 17 encompass method of characterizing a sample of claim 1 followed by administering a treatment, just as in claims 47 and 49.
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.
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.
4. Claims 1-3, 5, 8-20, 31, 32 and 35-52 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.
5. Claim 1 is vague and ambiguous for reasons that follow. First, the claim recites limitation “characterizing a white blood cell sample” without any active, objective and repeatable physical steps that provide for meaningful support of the limitation. Note that “using cytometry” also fails to set forth any steps involved in the process of “using.” Therefore, it is unclear what method/process Applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Second, the claim is indefinite insofar it recites the term “deficiency in regulatory or suppressive immune cells.” It is not obvious from the claim or the specification as filed what deficiency is intended by the claim, what specific immune cells are included or excluded from the deficiency, and what is the measure to evaluate the deficiency. Since deficiency is a critical element of the claimed method, failure to define what it stands for renders the claim indefinite. Finally, the claim broadly recites “increased activated immune cells in the sample,” and it is not obvious whether the limitation is intended to encompass cell numbers, quantity, or cell volume, quality. Clarification is required.
6. Applicant is advised that one of the purposes of the 112, second paragraph is to provide a clear warning to others as to what constitutes infringement of the patent (see, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). The test for definiteness under 35 U.S.C. § 112, second paragraph, is whether “those skilled in the art would understand what is claimed when the claim is read in light of the specification.” Orthokinetics, Inc. v. Safety Travel Chairs, Inc., 806 F .2d 1565 (Fed. Cir. 1986) (citations omitted).
In precedential decision Ex parte Kenichi Miyazaki, Appeal 2007-330, BPAI stated “In particular, rather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amendable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph.”
Further, the federal Circuit stated in Halliburton Energy Servs.:
When a claim limitation is defined in purely functional terms, the task of determining whether that limitation is sufficiently definite is a difficult one that is highly dependent on context (e.g., the disclosure in the specification and the knowledge of a person of ordinary skill in the relevant art area). We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiner demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.
Halliburton Energy Servs. V. M-ILLC 514 F .3d 1244, 1255 (Fed. Cir. 2008) (emphasis added).
7. Claim 9 is indefinite because it specifically requires identifying clusters of leukocytes, however, fails to recite active steps that provide for identification.
8. Similarly, claim 10 further narrows “identifying” to various analyses without any positive and meaningful defining steps that are associated with performing the intended activity. This renders the claim indefinite.
9. Claim 11 is indefinite wherein it recites functional language. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.” In the instant case, the claim recites identifying clusters of leukocytes as in claim 10 but then defines it —clusters of leukocyte segregate between healthy individuals and individuals with ALS— by functional language. While a functional limitation can provide a patentable distinction (limit the claim scope) by imposing limits on the function of a structure, material or action, in the instant case it is unclear what material/structural or manipulative differences are encompassed by recitation of “segregate.”
10. Claim 12 appears not further limiting. Briefly, unless there is another form of ALS, such as medium ALS, the ALS is either early or late. Thus, claim 12 is either indefinite or a duplicate of claim 11.
11. Claim 18 recites the limitation "FoxP3+" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
12. Claim 19 recites the limitation "mature B cells" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
13. Claim 20 recites the limitation "CD4 T cells" in claim 1. There is insufficient antecedent basis for this limitation in the claim. Also, claim 20 recites “wherein” twice, which renders the claim indefinite because it is not obvious whether the “CD4 T cells increased” requirement applies to all the limitations that follow the second “wherein.”
14. Claim 31 is indefinite for reference to Figures within the claims. See MPEP 2173.05(s), Reference to Figures or Tables, which states, “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
15. Claim 32 is indecipherable as written. First, it is not obvious what stands for a sample comprising a phenotype. Next the claim recites a reference to depiction of clusters by numbers, wherein the clusters are grouped into at least three categories separated within and between by “or,” which makes no sense. Applicant is advised to rewrite the claim to better express claimed subject matter.
16. Claim 35 recites steps (b), analyzing a second white blood sample, and (c) determining a deficiency, without any active physical steps that allow delineation of what provides for analyzing and determining. This renders the claim indefinite.
17. Claim 36 is grammatically awkward. Briefly, “the method of claim 35, the patient has an increased deficiency” appears missing “wherein;” and “compared to a white blood cell sample from a patient using cytometry” makes no sense. Moreover, the claim depends from claim 1, which already is limited to indication that the patient has ALS, thus making the final step of claim 35 vague and ambiguous. Applicant is advised to rewrite the claim to better express claimed subject matter.
18. Claim 44 is vague and indefinite insofar as it employs the term “clinically meaningful decline” as a limitation. This term is not known in the pertinent art of record as being associated with particular clinical conditions. Moreover, because the instant specification does not identify that property or combination of properties which is unique to and, therefore, definitive of a “clinically meaningful decline”, an artisan cannot determine if a decline from baseline, which meets all of the other limitations of a claim, would then be included or excluded from the claimed subject matter by the presence of this limitation.
19. Claim 52 recites the limitation "the method assessing progression of ALS" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
20. Claims 2-3, 5, 8, 13-17, 32, 37-43 and 45-51 are indefinite for being dependent from indefinite claim(s).
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.
21. Claims 2, 5, 42 and 51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 2 and 5 specifically require possession of antibodies that specifically bind granulocytes, monocytes, dendritic cells, Y cells, B cells, NK cells, immune activating cells and immune suppressive cells. Claims 42 and 51 recite a genus of immune modulating agents that are critical to practice the instant claimed methods. The claims do not require that the antibodies or agents possess any particular conserved structure or other disclosed distinguishing feature. Thus, the claims are drawn to a genus of antibodies that is defined by reference to the binding antigen and a genus of compounds defined by reference to their ability to modulate immune response and be suitable to treat ALS. However, the instant specification fails to describe the entire genus of molecular embodiments, which are encompassed by these claims.
MPEP §2163(I)(A) states:
“The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional or known in the art. Consider the claim "A gene comprising SEQ ID NO:1." The claim may be construed to include specific structures in addition to SEQ ID NO:1, such as a promoter, a coding region, or other elements. Although SEQ ID NO:1 is fully disclosed, there may be insufficient description of other structures embraced by the claim (e.g., promoters, enhancers, coding regions, and other regulatory elements).”
“An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. For example, the amino acid sequence of a protein along with knowledge of the genetic code might put an inventor in possession of the genus of nucleic acids capable of encoding the protein, but the same information would not place the inventor in possession of the naturally-occurring DNA or mRNA encoding the protein. See In re Bell, 991 F.2d 781, 26 USPQ2d 1529 (Fed. Cir. 1993); In re Deuel, 51 F.3d 1552, 34 USPQ2d 1210 (Fed. Cir. 1995) (holding that a process could not render the product of that process obvious under 35 U.S.C 103).”
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factors present in the claims is a requirement that antibodies bind, all or separately, granulocytes, monocytes, dendritic cells, Y cells, B cells, NK cells, immune activating cells and immune suppressive cells, and the agents modulate, such as produce any change, immune response. There is not even identification of any particular portion of the structure of antibody that must be conserved, and there is no reference to any specific chemical class of immune modulating agents. The specification does not provide a complete structure of those antibodies that specifically bind granulocytes, monocytes, dendritic cells, Y cells, B cells, NK cells, immune activating cells and immune suppressive cells, as well as immune modulating agents, and fails to provide a representative number of species for the recited genus of antibodies and a genus of agents. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited groups of molecular compounds.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of antibodies and genus of immune modulating agents, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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.
22. Claims 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Method claim(s) 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52, broadly drawn to methods for diagnosis of amyotrophic lateral sclerosis (ALS), set forth laws of nature by reciting relationship between changes in the levels of naturally occurring immune cells and the pathology itself. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for reasons that follow.
The subject matter eligibility under 35 U.S.C. 101 of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products) was confirmed by the U.S. Supreme Court decisions including Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. , 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. , 132 S. Ct. 1289, 101 USPQ2d 1961 (2012). "[L]aws of nature, natural phenomena, and abstract ideas" are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. (2010). "Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalkv. Benson, 409 U. S. 63, 67 (1972).
In brief, in Prometheus, a method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder is the focus. This method comprises a) administering 6-thioguanine to patients and b) determining the level of 6-thioguanine in the patients and c) correlate the level of 6-thioguanine, i.e. a certain level/red blood cells, with the decision whether a need for increase or decrease the amount of 6-thioguanine treatment in said patients.
In Prometheus, the Court found that "[i]f a law of nature is not patentable, neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law." Flook, 437 U. S., at 590; see also Bilski, 561 U. S., ("[T]he prohibition against patenting abstract ideas 'cannot be circumvented by'.., adding 'insignificant post-solution activity'" (quoting Diehr, supra, at 191-192)).
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
In the instant case, based upon an analysis with respect to the claim as a whole, claims 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52 are determined to be directed to a judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 74618) dated December 16, 2014 and 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52 are directed to a process. (Step 1: Yes).
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility. First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea). If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent-eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew). The instant claims 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52 encompass changes in the levels T cells, B cells and NK immune cells and pathology of ALS, the process that is governed by a law of nature and thus is a judicial exception. The immune cells recited within the claims are naturally occurring blood cells that are expressed differently during pathology of ALS apart from any human action. The relation between the levels of expression of the T, B and NL cells and pathology of ALS exists in principle and is a consequence of the ways these cells are produced by the body, entirely natural process, a natural phenomenon, and thus a judicial exception (Step 2A/1: Yes). Next, prong two of Step 2A requires identifying whether there are additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. “Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to monopolize the exception. In the instant case, the claims do not recite any additional elements to integrate the judicial exception into a practical application because all the steps of the claimed methods are limited to only those that identify and measure naturally occurring blood cells during a naturally occurring pathology. (Step 2A/2: No).
Finally, claims 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52 do not recite any elements, or combinations of elements to ensure that the claim as a whole amounts to significantly more than the judicial exception because the active steps of the claims—identifying and measuring the numbers of cell by means of cytometry—represent routine steps that are recited at a high level of generality and encompass well-understood and purely conventional routine techniques in the art. (Step 2B: No).
Thus, for reasons fully explained above, claims 1-3, 5, 8-15, 18-20, 31, 32, 35-38, 44-46 and 52 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
Conclusion
23. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA N CHERNYSHEV whose telephone number is (571)272-0870. The examiner can normally be reached 9AM to 5:30PM, Monday to Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OLGA N CHERNYSHEV/Primary Examiner, Art Unit 1675
September 30, 2026
Prosecution Insights