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 .
Drawings
The drawings were received on 29 July 2025. These drawings are acceptable.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Claim Rejections - 35 USC § 112, (b) / Second Paragraph
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.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-07.2022]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“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 examiners 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.”
***
During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B, which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10.2019], which states in part:
A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Holding and Rationale
Claims 1-2, 4-5, 8-9, 14-15, and 21-37 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 is indefinite with respect to what constitutes the metes and bounds by which “the detection agent interacts with the oligonucleotide probe to produce a detectable signal”. Said claim 1 is also indefinite with respect to what constitutes the metes and bounds of “a detectable signal”, and by which mean(s) it is “detectable” when one performs the step of “detecting”.
Claim 1 is indefinite with respect to what constitutes the metes and bounds of “a substrate”.
Claim 1 is indefinite with respect to what constitutes the metes and bounds of “a detectable signal” and how such is detected.
The term “more” in claims 1-2, 8, 14, 15, 29, 30, 33, 36, and 37 is a relative term which renders the claims indefinite. The term “more” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 2, 4-5, 8-9, 14-15, and 21-37, which depend from claim 1, fail to overcome all of the above identified issues and are similarly rejected.
Claim 9 is indefinite with respect to what the abbreviation “LNA” means. It is noted that claim 9 depends from claim 2, and that the amendment to claim 2 deleted language providing the meaning.
Response to argument
Applicant’s representative, at pages 11-18 of the response of 29 July 2025, hereinafter the response, traverses the rejection of claims for not satisfying the requirements of 35 USC 112(b).
At page 13, bridging to page 14, of the response, said representative asserts:
The Office Action alleged that examined claim 1 is “indefinite with respect to what constitutes the metes and bounds by which ‘the detection agent interacts with the oligonucleotide probe to produce a detectable signal’ and by which means it is ‘detectable’ and one performs the step of ‘detecting’ ” (Office Action at p.9, para. 27). Applicant respectfully disagrees.
Applicant submits that various agents that could be used to detect the presence of an oligonucleotide probe in a sample and methods of detection were well known to persons of ordinary skill in the art at the time of filing of the instant application. Such skilled persons would further understand that, depending on the agent selected, both the mode of interaction (e.g., via non-covalent interactions, covalent interactions, etc.) and the detection signal (e.g., colorimetric, non-colorimetric, fluorometric, etc.) may vary. For example, paragraphs [0066]-[0069] of the specification as originally filed describe that a detection agent can interact (e.g., bind or hybridize) with an oligonucleotide probe that is, for example, covalently linked to a label, to produce a detectable signal (e.g. colorimetric, non-colorimetric, or fluorometric), and steps by which the detectable signal can be measured (e.g., excitation and emission wavelengths and signal detection times). Accordingly, in view of the knowledge of a skilled person of the art and the detailed description of detection agents and detection methods disclosed in the instant application, one of ordinary skill in the art would understand the clear meanings of “interacts,” “detectable signal,” “detectable,” and “detecting” as recited in the claims presented herewith. (Emphasis added)
The above cited arguments have been considered and have not been found persuasive. As evidenced above, the mode of interaction and means and methos for detection “may vary”. While attention has been directed to paragraphs [0064]-[0069] of the disclosure, it is noted that specific embodiments found in the disclosure cannot be read into the claims. In support of this position , attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
As evidenced above assertions have been made that “one of ordinary skill in the art would understand the clear meanings of “interacts,” “detectable signal,” “detectable,” and “detecting” as recited in the claims”. This argument has been fully considered and has not been found persuasive. Attention is directed to MPEP 2145 I [R-01.2024].
An argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
A review of the response fails to find where any affidavit or declaration has been provided.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
At page 14 of the response said representative traverses the rejection of claims as it relates to what constitutes the metes and bounds of a “substrate”. As asserted to therein:
Applicant submits that various substrates that could be used in oligonucleotide detection assays were well known to persons of ordinary skill in the art at the time of filing of the instant application. For example, microplates (e.g., 96-well plates) were well known by persons of skill in the art at the time of filing of the instant application and described throughout the instant application (e.g., paras. [0061]-[0064] and [0095] of the specification as originally filed). Accordingly, in view of the knowledge of a skilled person in the art and the detailed description of exemplary detection assay substrates, Applicant submits that the skilled person would understand the clear meaning of the term “substrate” as recited in the claims presented herewith.
The above cited argument has been considered and has not been found persuasive towards the withdrawal of the rejection. The question is not what was known but rather, what does applicant want to have the claims encompass. While the disclosure may teach of microplates (e.g.., 96-well plates)”, such a limitation cannot be read into the claims. In support of this position attention is again directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
At page 14, last paragraph, bridging to page 15 of the response said representative traverses the rejection of claims as it relates to what constitutes the metes and bounds of “a detectable signal” and how such is detected. As asserted to therein:
For the reasons already provided above, Applicant submits that in view of the knowledge of a skilled person in the art and the detailed description of detection signals disclosed in the instant application, the skilled person would understand the clear meaning of “detectable signal” as recited in the claims presented herewith.
This argument has been fully considered and has not been found persuasive. Attention is directed to MPEP 2145 I [R-01.2024].
An argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
A review of the response fails to find where any affidavit or declaration has been provided.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
At page 15 of the response said representative traverses the rejection of claims as it relates to what constitutes the metes and bounds of the relative term “more”. As is asserted to therein:
Applicant submits that one of ordinary skill in the art would understand the term “one or more” to be synonymous with “at least one” indicating that there is a requisite minimum of one DNA residue (examined claim 8) or a requisite minimum of one tissue of a subject (examined claim 29), with no upper limit (e.g., two, three, four, five, six, seven, eight, nine, ten, or more). Similarly, one of ordinary skill in the art would understand the term “two or more” to be synonymous with “at least two,” indicating that there is a requisite minimum of two nucleases (examined claims 1, 14, 15), a requisite minimum of two locked nucleic acids (examined claim 2), or a requisite minimum of two tissues of a subject (examined claim 30) ), with no upper limit (e.g., three, four, five, six, seven, eight, nine, ten, or more). Accordingly, Applicant submits that the term “more” as recited in the claims presented herewith is not a “relative term,” but instead a definitive term to mean any number more than the requisite minimum (e.g., one or two).
A review of the response fails to find where any declaration has been provided, much less one that presents evidence that “one or more” would be construed as being “synonymous with ‘at least one’”. Attention is again directed to MPEP 2145 I [R-01.2024].
An argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-2, 4-5, 8-9, 14-15, and 21-37 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 Rejections - 35 USC § 112, Enablement
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-5, 8-9, 14-15, and 21-37 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As set forth in Cephalon Inc. v. Watson Pharmaceuticals Inc. 105 USPQ2d 1817, 1821 (CAFC, 2013):
To satisfy section 112 of the 1952 Patent Act, the specification must enable a person of ordinary skill in the art to make and use the invention. 35 U.S.C. § 112, ¶1. This requirement is met when at the time of filing the application one skilled in the art, having read the specification, could practice the invention without “undue experimentation.” In re Wands, 858 F.2d 731, 736-37 [8 USPQ2d 1400] (Fed. Cir. 1988). Whether undue experimentation is required “is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” ALZA Corp. v. Andrx Pharms., LLC, 603 F.3d 935, 940 [94 USPQ2d 1823] (Fed. Cir. 2010) (citing Wands, 858 F.2d at 737).
The following factors may be considered when determining if a disclosure requires undue experimentation:
(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
Wands, 858 F.2d at 737 (“Wands factors”); Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1372 [52 USPQ2d 1129] (Fed. Cir. 1999) (“The Wands factors, when applied from the proper temporal perspective … are a useful methodology for determining enablement….”). These factors while illustrative are not mandatory. Enzo Biochem, Inc., 188 F.3d at 1371. What is relevant depends on the facts, and although experimentation must not be undue, a reasonable amount of routine experimentation required to practice a claimed invention does not violate the enablement requirement. Id. The burden of proof here is on Watson to show that the Khankari patents are invalid for lack of enablement by clear and convincing evidence. See Auto. Tech. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 1281 [84 USPQ2d 1109] (Fed. Cir. 2007).
The breadth of the claims, The nature of the invention & The state of the prior art
Claims 1, 2, 21, 22, 29, 30, and 35 are deemed to be representative and, for convenience, are reproduced below.
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As evidenced above, the claims are to a “method” which requires the hybridization of “oligonucleotides” that are a target and in a “sample” to “oligonucleotide probe[s]”. The target oligonucleotide in the sample is without bound.
Applicant, at page 10, paragraph [0052] of the disclosure provides the following definition for the subject from which the sample is derived As stated therein:
[0052] Subject: As used herein, the term "subject" refers an organism, typically a mammal (e.g., a human, in some embodiments including prenatal human forms). In some embodiments, a subject is suffering from a relevant disease, disorder or condition. In some embodiments, a subject is susceptible to a disease, disorder, or condition. In some embodiments, a subject displays one or more symptoms or characteristics of a disease, disorder or condition. In some embodiments, a subject does not display any symptom or characteristic of a disease, disorder, or condition. In some embodiments, a subject is someone with one or more features characteristic of susceptibility to or risk of a disease, disorder, or condition. In some embodiments, a subject is a patient. In some embodiments, a subject is an individual to whom diagnosis and/or therapy is and/or has been administered. (Emphasis added)
Attention is directed to the following publications which teach of the enormity of the various genera of organisms, be it virus, plants, insects, bacteria, mammals, and species encompassed by the subfamily Murinae as the detection of any and all oligonucleotides that are all genes from all members of the various genera are encompassed by the instant claims.
“Viruses” (Wikipedia.com, accessed 08 September 2023), teaches:
An enormous variety of genomic structures can be seen among viral species; as a group, they contain more structural genomic diversity than plants, animals, archaea, or bacteria. There are millions of different types of viruses, although fewer than 7,000 types have been described in detail. (Emphasis added)
“How many species of bacteria are there” (wisegeek.com; accessed 21 January 2014) teaches:
Currently, estimates of the total number of species of bacteria range from about 10 million to a billion, but these estimates are tentative, and may be off by many orders of magnitude. By comparison, there are probably between 10 and 30 million species of animals, the vast majority of them insects. The number of scientifically recognized species of animals is about 1,250,000. There are almost 300,000 recognized species of plants.
“Fungi,” (Wikipedia.com; accessed 08 September 2023), teaches:
As of 2020, around 148,000 species of fungi have been described by taxonomists,[6] but the global biodiversity of the fungus kingdom is not fully understood.[48] A 2017 estimate suggests there may be between 2.2 and 3.8 million species.[5]
“Insect”, (Wikipedia.com; accessed 09/10/2020) teaches:
Insects are the most diverse group of animals; they include more than a million described species and represent more than half of all known living organisms. The total number of extant species is estimated at between six and ten million; potentially over 90% of the animal life forms on Earth are insects.
“Plant,” (Wikipedia.com; accessed 08 September 2023) teaches:
There are about 380,000 known species of plants, of which the majority, some 260,000, produce seeds.
“Mammal,” (Wikipedia.com; accessed 08 September 2023) teaches:
According to Mammal Species of the World, which is updated through periodic editions, 5,416 species were identified in 2006. These were grouped into 1,229 genera, 153 families and 29 orders.[5]
“Murinae,” (Wikipedia.com, accessed 10 June 2024) teaches:
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families except the Cricetidae and Muridae, and is larger than all mammal orders except the bats and the remainder of the rodents.
“Fish,” (Wikipedia.com, accessed 08 September 2023) teaches:
Fish are abundant in most bodies of water. They can be found in nearly all aquatic environments, from high mountain streams (e.g., char and gudgeon) to the abyssal and even hadal depths of the deepest oceans (e.g., cush-eels and snailfish), although no species has yet been documented in the deepest 25% of the ocean.[4] At 34,300 described species, fish exhibit greater species diversity than any other group of vertebrates.[5]
“Archaea,” Wikipedia.com (accessed 08 September 2023), teaches:
The classification of archaea into species is also controversial. Ernst Mayr defined a species as a group of interbreeding organisms which are reproductively isolated, but this is of no help since archaea only reproduce asexually.[37]
Archaea show high levels of horizontal gene transfer between lineages. Some researchers suggest that individuals can be grouped into species-like populations given highly similar genomes and infrequent gene transfer to/from cells with less-related genomes, as in the genus Ferroplasma.[38] On the other hand, studies in Halorubrum found significant genetic transfer to/from less-related populations, limiting the criterion's applicability. Some researchers question whether such species designations have practical meaning.[40]
Current knowledge on genetic diversity is fragmentary, so the total number of species cannot be estimated with any accuracy.[22] (Emphasis added)
“Algae,” Wikipedia.com (accessed 03-04-2016) teaches:
The most recent estimate suggests 72,500 algal species worldwide.
“Protozoa,” Wikipedia.com (accessed 05-11-2016), teaches:
The classification of protozoa has been and remains a problematic area of taxonomy. Where they are available, DNA sequences are used as the basis for classification; however, for the majority of described protozoa, such material is not available. (Emphasis added)
Attention is directed to “Eukaryotic Genome Complexity” (Pray, Nature Education, 1(1):36, 2008, pages 1-4.). As seen therein, a table of estimated protein encoding genes in different genomes is provided.
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The quantity of experimentation necessary
The quantity of experimentation necessary is great, on the order of many man-years, and then with little if any reasonable expectation of successfully enabling the full scope of the claims. In support of this position, it is noted that the art suggests that there are millions of species of viruses and fungi that are yet to be identified and characterized. Assuming, arguendo, that one were to identify a new virus or fungus every day, 365 days a year, and to also determine in the same day the nucleotide sequence of the genome of said organism, and additionally, identify oligonucleotide probes that would be useful in the identification of a target sequence found in said new organism wherein said target sequence has utility under 35 USC 101, it would take approximately 2739 years to sequence even 1 million viruses or fungi. Clearly, such an effort to enable the full scope of that claimed would constitute undue experimentation. In support of this position attention is directed to Cephalon, 1823:
Permissible experimentation is, nevertheless, not without bounds. This court has held that experimentation was unreasonable, for example, where it was found that eighteen months to two years’ work was required to practice the patented invention. See, e.g., White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] (Fed. Cir. 1983). Likewise, we have held that the amount of experimentation would be undue where: (1) the specification lacks guidance by teaching away from the subject matter that was eventually claimed; and (2) there is evidence of the patentee's own failures to make and use the later claimed invention at the time of the application. See, e.g., AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244 [68 USPQ2d 1280] (Fed. Cir. 2003). (Emphasis added)
Alternatively, even if the claimed method was limited to the detection of known organisms, the selection of probes and primers would also constitute undue experimentation. In support of this position, it is noted that if one were to utilize a probe that was but 20 nucleotides long, and to then substitute each of the positions with the four common dNTPs, there are some 420, or 1.099 x 1012 different sequences to screen/evaluate. In support of the position that to screen such a number of candidate molecules would constitute undue experimentation, attention is directed to Wyeth v. Abbott Laboratories 107 USPQ2d 1273, 1276 (Fed. Cir. June 2013):
The remaining question is whether having to synthesize and screen each of at least tens of thousands of candidate compounds constitutes undue experimentation. We hold that it does. Undue experimentation is a matter of degree. Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 [70 USPQ2d 1321] (Fed. Cir. 2004) (internal quotation omitted). Even “a considerable amount of experimentation is permissible,” as long as it is “merely routine” or the specification “provides a reasonable amount of guidance” regarding the direction of experimentation. Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d 1342, 1360-61 [47 USPQ2d 1705] (Fed. Cir. 1998) (internal quotation omitted). Yet, routine experimentation is “not without bounds.” Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339 [105 USPQ2d 1817] (Fed. Cir. 2013). (Emphasis added)
Our cases have described limits on permissible experimentation in the context of enablement. For example, in ALZA Corp. v. Andrx Pharmaceuticals, LLC, we affirmed a judgment of nonenablement where the specification provided “only a starting point, a direction for further research.” 603 F.3d 935, 941 [94 USPQ2d 1823] (Fed. Cir. 2010) (internal quotation omitted). We concluded that one of ordinary skill “would have been required to engage in an iterative, trial-and-error process to practice the claimed invention even with the help of the … specification.” Id. at 943. In Cephalon, although we ultimately reversed a finding of nonenablement, we noted that the defendant had not established that required experimentation “would be excessive, e.g., that it would involve testing for an unreasonable length of time.” 707 F.3d at 1339 (citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] (Fed. Cir. 1983)). Finally, in In re Vaeck, we affirmed the PTO's nonenablement rejection of claims reciting heterologous gene expression in as many as 150 genera of cyanobacteria. 947 F.2d 488, 495-96 [20 USPQ2d 1438] (Fed. Cir. 1991). The specification disclosed only nine genera, despite cyanobacteria being a “diverse and relatively poorly understood group of microorganisms,” with unpredictable heterologous gene expression. Id. at 496. (Emphasis added)
Here, the specification similarly discloses only a starting point for further iterative research in an unpredictable and poorly understood field. Synthesizing candidate compounds derived from sirolimus could, itself, require a complicated and lengthy series of experiments in synthetic organic chemistry. Even putting the challenges of synthesis aside, one of ordinary skill would need to assay each of at least tens of thousands of candidates. Wyeth's expert conceded that it would take technicians weeks to complete each of these assays. The specification offers no guidance or predictions about particular substitutions that might preserve the immunosuppressive and antirestenotic effects observed in sirolimus. The resulting need to engage in a systematic screening process for each of the many rapamycin candidate compounds is excessive experimentation. We thus hold that there is no genuine dispute that practicing the full scope of the claims, measured at the filing date, required undue experimentation. (Emphasis added)
The amount of direction or guidance presented,
The amount of guidance provided is limited, generally prophetic, and not commensurate with the scope of the claims.
The presence or absence of working examples
The disclosure has been found to comprise but a single example, “Example 1: Oligonucleotide detection assay”, at page 20 of the as-filed disclosure.
The disclosure has been found to comprise a “Sequence Listing”. Said Sequence Listing has been found to comprise a total of 3 DNA oligonucleotides, each of which is identified as being an “Artificial Sequence”. In short, the disclosure has not been found to disclose the nucleotide sequence for any target nucleic acid in any “organism”, much less disclose nucleotide sequences found in any “organism” which has utility under 35 USC 101.
As can be seen in claim 35, the method is focused on assessing the modulation of the expression of “the target protein… dystrophin.” The disclosure has not been found to provide the amino acid sequence of the dystrophin for any organism that has such, much less provide the nucleotide sequence for any mRNA that encode same, nor provide any antibodies that would bind to said protein.
The nucleotide sequence of the oligonucleotides, be they target or probe, and the amino acid sequence of the protein are deemed to constitute essential material.1
The predictability or unpredictability of the art
As noted in In re Fisher 166 USPQ 18 (CCPA, 1970):
In cases involving predictable factors, such as that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.
Attention is also directed to Wyeth v. Abbott Laboratories 107 USPQ2d 1273 (Fed. Cir. June 2013):
The remaining question is whether having to synthesize and screen each of at least tens of thousands of candidate compounds constitutes undue experimentation. We hold that it does. Undue experimentation is a matter of degree. Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 [70 USPQ2d 1321] (Fed. Cir. 2004) (internal quotation omitted). Even “a considerable amount of experimentation is permissible,” as long as it is “merely routine” or the specification “provides a reasonable amount of guidance” regarding the direction of experimentation. Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d 1342, 1360-61 [47 USPQ2d 1705] (Fed. Cir. 1998) (internal quotation omitted). Yet, routine experimentation is “not without bounds.” Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339 [105 USPQ2d 1817] (Fed. Cir. 2013).
Our cases have described limits on permissible experimentation in the context of enablement. For example, in ALZA Corp. v. Andrx Pharmaceuticals, LLC, we affirmed a judgment of nonenablement where the specification provided “only a starting point, a direction for further research.” 603 F.3d 935, 941 [94 USPQ2d 1823] (Fed. Cir. 2010) (internal quotation omitted). We concluded that one of ordinary skill “would have been required to engage in an iterative, trial-and-error process to practice the claimed invention even with the help of the … specification.” Id. at 943. In Cephalon, although we ultimately reversed a finding of nonenablement, we noted that the defendant had not established that required experimentation “would be excessive, e.g., that it would involve testing for an unreasonable length of time.” 707 F.3d at 1339 (citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] (Fed. Cir. 1983)). Finally, in In re Vaeck, we affirmed the PTO's nonenablement rejection of claims reciting heterologous gene expression in as many as 150 genera of cyanobacteria. 947 F.2d 488, 495-96 [20 USPQ2d 1438] (Fed. Cir. 1991). The specification disclosed only nine genera, despite cyanobacteria being a “diverse and relatively poorly understood group of microorganisms,” with unpredictable heterologous gene expression. Id. at 496.
Here, the specification similarly discloses only a starting point for further iterative research in an unpredictable and poorly understood field. Synthesizing candidate compounds derived from sirolimus could, itself, require a complicated and lengthy series of experiments in synthetic organic chemistry. Even putting the challenges of synthesis aside, one of ordinary skill would need to assay each of at least tens of thousands of candidates. Wyeth's expert conceded that it would take technicians weeks to complete each of these assays. The specification offers no guidance or predictions about particular substitutions that might preserve the immunosuppressive and antirestenotic effects observed in sirolimus. The resulting need to engage in a systematic screening process for each of the many rapamycin candidate compounds is excessive experimentation. We thus hold that there is no genuine dispute that practicing the full scope of the claims, measured at the filing date, required undue experimentation.
In view of the breadth of scope clamed, the limited guidance provided, the unpredictable nature of the art to which the claimed invention is directed, and in the absence of convincing evidence to the contrary, the claims are deemed to be non-enabled by the disclosure.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-2, 4-5, 8-9, 14-15, and 21-37 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 enablement requirement.
Response to argument
Applicant’s representative, at pages 18-19 of the response, traverses the rejection of claims under 35 USC 112(a) for not satisfying the enablement requirement. As is asserted therein:
The Office Action describes the genetic diversity of various organisms (Office Action, pp. 13-17, paras 45-59). Applicant respectfully submits that the Office Action has misunderstood what is being claimed in the instant application. Applicant is not claiming all known (and as-yet unknown) oligonucleotides from all known (and as-yet unknown) organisms on the planet. Indeed, the examined claims and amended claims presented herein do not claim oligonucleotides at all. Rather, as described above, the claims are directed to a method of determining the presence of an oligonucleotide in a sample. One of ordinary skill in the art would understand that the specific sequence and/or organismal source of an oligonucleotide is only relevant insofar as it is selected by one performing the claimed method as the oligonucleotide whose presence is to be determined. One of ordinary skill would further understand that the claimed method could be used for the detection of any oligonucleotide in a sample and that no undue or unreasonable experimentation would be required in order to perform the steps of the method as claimed. (Emphasis in original)
The above arguments have been considered and have not been found persuasive. In support of this position attention is directed to page 17 of the response where said representative, in response to a rejection of claims under 35 USC 112(b), is asserted:
The claims presented herewith are directed to a method of determining the presence of an
oligonucleotide in a sample. One of ordinary skill in the art would understand that such a method could be applied to any tissue sample collected from any organism. Accordingly, Applicant submits that the term “tissue” as recited in the claims presented herewith is definite and whose meaning is clearly understood by persons of ordinary skill in the art. (Emphasis added)
As is evidenced above, applicant asserts that the tissue can be of any type and that it can be collected from any source. Such breadth of scope fairly encompasses all manner of tissues found in every species of every type of organism, be it known at the time of filing or at some point in the future. The disclosure has been found to comprise a Sequence Listing that comprises a total of 3 sequences, each of which is DNA, an “Artificial Sequence” and are either 19 or 25 nucleotides in length. The disclosure has not been found to disclose the nucleotide sequence for any oligonucleotide that is found within any chromosome of any organism, much less oligonucleotides, be they target or probes, that have a specific and substantial utility.
It is well settled that an applicant must enable the full scope of that which is claimed. In support of this position attention is directed to the unanimous U.S. Supreme Court decision in Amgen Inc., et al. v. Sanofi et al. 598 U.S. ___ (2023):
Our decisions in Morse, Incandescent Lamp, and Holland Furniture reinforce the simple
statutory command. If a patent claims an entire class of processes, machines,
manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405, 419 (1908) (“[T]he claims measure the invention.”). (Emphasis added)
***
To be fair, Amgen does not dispute this much. It freely admits that it seeks to claim for
itself an entire universe of antibodies. Still, it says, its broad claims are enabled because
scientists can make and use every undisclosed but functional antibody if they simply
follow the company’s “roadmap” or its proposal for “conservative substitution.”
We cannot agree. These two approaches amount to little more than two research
assignments… Whether methods like a “roadmap” or “conservative substitution” might
suffice to enable other claims in other patents—perhaps because, as this Court suggested
in Incandescent Lamp, the inventor identifies a quality common to every functional
embodiment, supra, at 13—they do not here. They leave a scientist about where Sawyer
and Man left Edison: forced to engage in “painstaking experimentation” to see what
works. 159 U. S., at 475.