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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-26, in the reply filed on 22 October 2025 is acknowledged.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
Each panel needs to be individually labeled, e.g., FIG. 4E, not “4D (Cont’d)”. See 37 CFR 1.84(u)(1) and (2),
In Figure(s) 1-8 the reference characters, sheet numbers, and view numbers are not all oriented in the same direction so as to avoid having to rotate the sheet. See 37 CFR 1.84(p)(1).
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
INFORMATION ON HOW TO EFFECT DRAWING CHANGES
Replacement Drawing Sheets
Drawing changes must be made by presenting replacement sheets which incorporate the desired changes and which comply with 37 CFR 1.84. An explanation of the changes made must be presented either in the drawing amendments section, or remarks, section of the amendment paper. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). A replacement sheet must include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of the amended drawing(s) must not be labeled as “amended.” If the changes to the drawing figure(s) are not accepted by the examiner, applicant will be notified of any required corrective action in the next Office action. No further drawing submission will be required, unless applicant is notified.
Identifying indicia, if provided, should include the title of the invention, inventor’s name, and application number, or docket number (if any) if an application number has not been assigned to the application. If this information is provided, it must be placed on the front of each sheet and within the top margin.
Annotated Drawing Sheets
A marked-up copy of any amended drawing figure, including annotations indicating the changes made, are required by the examiner. The annotated drawing sheet(s) must be clearly labeled as “Annotated Sheet” and must be presented in the amendment or remarks section that explains the change(s) to the drawings.
Timing of Corrections
Applicant is required to submit acceptable corrected drawings within the time period set in the Office action. See 37 CFR 1.85(a). Failure to take corrective action within the set period will result in ABANDONMENT of the application.
If corrected drawings are required in a Notice of Allowability (PTOL-37), the new drawings MUST be filed within the THREE MONTH shortened statutory period set for reply in the “Notice of Allowability.” Extensions of time may NOT be obtained under the provisions of 37 CFR 1.136 for filing the corrected drawings after the mailing of a Notice of Allowability.
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.”
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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 1-26 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 of “a different type of RNA” and “different types of probes”.
The terms “multiple”, “complementary”, “more”, “different pluralities”, “optical labels”, and “differs” in claim 1 are relative terms which render the claim indefinite. The terms “multiple”, “complementary”, “more”, “different pluralities”, “optical labels”, and “differs” are not defined by the claim, 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.
Claim 1 is indefinite with respect to what constitutes the metes and bounds of an “oligonucleotide”. A review of the disclosure fails to find where applicant has provided a closed definition for the term “oligonucleotide,” and a review of the art finds that there is not a single art-accepted definition. In support of this position, it is noted that Merriam-Webster.com (“Oligonucleotide definition,” Merriam-Webster.com; accessed 08-23-2017) provides the following exemplary definition:
[A] short nucleic-acid chain usually consisting of up to approximately 20 nucleotides. (Emphasis added)
US 2019/0002971 A1 (Kslover et al.), paragraph [0084], teaches:
In some embodiments, binding moieties comprise an oligonucleotide or analog thereof having a length in the range of from 6 to 60 nucleotides.
US 2009/0011943 A1 (Drmanac et al.), at paragraph [0116], teaches:
The length of capture oligonucleotides may vary widely, In one aspect, capture oligonucleotides and their complements in a bridging oligonucleotide have lengths in the range of from 10 to 100 nucleotides; and more preferably, in the range of from 10 to 40 nucleotides. (Emphasis added)
In comparison, US Patent 6,444,661 B1 (Barton et al.), column 6, first paragraph, states:
The probe oligonucleotide can be as short as about 8-10 bases, up to a length of several thousand bases: the probe can be as long or longer than the target polynucleotide. (Emphasis added)
“Oligonucleotide”, Wikipedia.com (accessed February 17, 2019) teaches:
A less than 100% yield of each synthetic step and the occurrence of side reactions set practical limits of the efficiency of the process so that the maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide residues. (Emphasis added)
When as here it is evident that there is not a single art-accepted meaning for the term, a question as to the metes and bounds of the claim exist.
Claim 1 is indefinite with respect to what constitutes the metes and bounds of a “reporter moiety”
Claims 2-25, which depend from claim 1, fail to overcome all of the above identified issues and are similarly rejected.
Claim 2 is indefinite with respect to 1) just which property/properties of the “optical signal” is/are being measured; and 2) what constitutes the metes and bounds of “different pluralities”.
The term “label regions”, or “label region”, in claims 3-11, 18 and 26 is a relative term which renders the claim indefinite. The term “label regions”, or “label region” is not defined by the claim, 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. .
The term “more” in claims 3, 16, 17, 19, and 26 is a relative term which renders the claims indefinite. The term “more” is not defined by the claim, 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.
The term “common species” and “different” in claim 22 are relative terms which render the claim indefinite. The terms “common species” and “different” are not defined by the claim, 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.
Claim Rejections - 35 USC § 112, First Paragraph / (a) - Written Description
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.
Standard for Written Description.
Attention is directed to MPEP 2163.02 Standard for Determining Compliance With the Written Description Requirement [R-07-2022]:
An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed. (Emphasis added)
Attention is also set directed to MPEP 2161.01 I [R-07-2022], wherein is stated:
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in Fiers v. Revel 25 USPQ2d 1601, 1604-5 (CAFC, January 1993):
We thus determined that, irrespective of the complexity or simplicity of the method of isolation employed, conception of a DNA, like conception of any chemical substance, requires a definition of that substance other than by its functional utility.
Fiers' attempt to distinguish Amgen therefore is incorrect. We also reject Fiers' argument that the existence of a workable method for preparing a DNA establishes conception of that material. (Emphasis added)
Conception of a substance claimed per se without reference to a process requires conception of its structure, name, formula, or definitive chemical or physical properties...
The difficulty that would arise if we were to hold that a conception occurs when one has only an idea of a compound, defining it by its hoped-for function, is that would-be inventors would file patent applications before they had made their inventions and before they could describe them. That is not consistent with the statute or the policy behind the statute, which is to promote disclosure of inventions.
Attention is also directed to MPEP 2163 Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, “Written Description” Requirement [R-01-2024], at part II ii):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).") (Emphasis added)
Attention is also directed to the decision of University of California v. Eli Lilly and Co. (CA FC, July 1997) 43 USPQ2d 1398 wherein is stated:
In claims involving chemical materials, generic formulas usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate written description of the claimed genus. In claims to genetic material, however, a generic statement such as “vertebrate insulin cDNA” or “mammalian cDNA,” without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what it achieves as a result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.
Thus, as we have previously held, a cDNA is not defined or described by the mere name cDNA,” even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA. See Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
Acknowledgement is made of the fact that the claims are to a method and not to a product. However, it is well settled that in order to satisfy the written description for a method, one must also disclose the molecules required to perform the method. In support of this position attention is directed to University of Rochester v. G.D. Searle & Co. 68 USPQ2D 1424 (W.D.N.Y. 2003) at 1433 (affirmed; University of Rochester v. G.D. Searle & Co. 69 USPQ2d 1886 (Fed. Cir. 2004)):
Plaintiff also argues that the requirements for written descriptions of claims to chemical compounds are irrelevant to this case because the '850 patent does not claim a compound, but a method of treatment by targeting PGHS-2 activity over PGHS-1 activity. Virtually any compound claim could be transformed into a method claim, however, simply by means of wording the claim in terms of a method of using the compound. With respect to the issue before the Court, then, this is little more than a semantic distinction without a difference. The claimed method depends upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment. It means little to “invent” a method if one does not have possession of a substance that is essential to practicing that method. Without that substance, the claimed invention is more theoretical than real; it is, as defendants argue, akin to “inventing” a cure for cancer by utilizing a substance that attacks and destroys cancer cells while leaving healthy cells alone. Without possession of such a substance, such a “cure” is illusory, and there is no meaningful possession of the method.
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What the inventors did not do, however, is succeed in taking the last, critical step of actually isolating such a compound, or at least of developing a process through which one skilled in the art would be directly led to such a compound. Absent that step, their discoveries, valuable though they might have been, did not blossom into a full-fledged, complete invention. Scientific discoveries, and theories based on those discoveries, frequently lay the groundwork for later inventions, but that does not make the discoverer the inventor as well.
Attention is also directed to the decision in Ariad Pharmaceuticals Inc. v. Eli Lilly & Co.
(Fed. Cir. 2010) 94 USPQ2d 1161, 1175, which teaches:
In accordance with Rochester, the ?516 patent must adequately describe the claimed methods for reducing NF-?B activity, including adequate description of the molecules that Ariad admits are necessary to perform the methods. (Emphasis added)
Holding and Rationale
Claims 1-26 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 1, 8-10, and 26 are deemed to be representative and, for convenience, are reproduced below.
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As evidenced above, the claimed method requires “a plurality of different types of probes” to hybridize to “a different type of RNA analyte in the sample”.
Applicant, at page 11 of the disclosure asserts:
Biological sample 10 can be any one of a variety of different types of samples.
Examples of biological sample 10 include, but are not limited to, tissue sections (e.g., fresh sections, fresh-frozen sections, formalin-fixed paraffin embedded sections), tissue biopsies, cells, cell suspensions, cell dispersions, cell cultures, and various bodily fluids such as blood, urine, interstitial fluid, and lymphatic fluid. (Emphasis added)
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Analyte 100 can be any of a variety of different analytes. In some embodiments, analyte 100 is an RNA species. In certain embodiments, analyte 100 is a DNA species. Other examples 15 of analyte 100 include, but are not limited to, antigens, peptides, proteins, and other amino-acid containing moieties, and oligonucleotides, including oligonucleotides containing DNA bases, RNA bases, both DNA and RNA bases, and synthetic bases, nucleic acid fragments, and lipids. Analyte 100 can be a clinically relevant biomarker, particularly a biomarker that is expressed in tumor tissue, in the tumor microenvironment, and tissues representative of other 20 disease states. Examples of such biomarkers include, but are not limited to: tumor markers such as Soxl0, SI00, pan-cytokeratin, PAX5, PAX8; immune cell identifiers such as CD3, CD4, CD8, CD20, FoxP3, CD45RA, CD45LCA, CD68, CD163, CDI le, CD33, HLADR; activation markers such as Ki67, granzyme B; and checkpoint-related markers such as TIM3, LAG3, PDI, PDLI, CTLA4, CD80, CD86, IDO-1, VISTA, CD47, CD26. (Emphasis added)
A review of the disclosure fails to find where applicant has provided any Sequence Listing, much less a Sequence Listing that comprises the nucleotide sequences for probes and targets encompassed by the claimed method.
Applicant’s nondisclosure of such essential material1 has not been found to satisfy the written description requirement. As noted above, it is well settled that in order to satisfy the written description requirement for a method, one must also disclose the molecules required to perform the method. In support of this position attention is directed to University of Rochester v. G.D. Searle & Co. 68 USPQ2D 1424 (W.D.N.Y. 2003) at 1433 (affirmed; University of Rochester v. G.D. Searle & Co. 69 USPQ2d 1886 (Fed. Cir. 2004)):
Plaintiff also argues that the requirements for written descriptions of claims to chemical compounds are irrelevant to this case because the '850 patent does not claim a compound, but a method of treatment by targeting PGHS-2 activity over PGHS-1 activity. Virtually any compound claim could be transformed into a method claim, however, simply by means of wording the claim in terms of a method of using the compound. With respect to the issue before the Court, then, this is little more than a semantic distinction without a difference. The claimed method depends upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment. It means little to “invent” a method if one does not have possession of a substance that is essential to practicing that method. Without that substance, the claimed invention is more theoretical than real; it is, as defendants argue, akin to “inventing” a cure for cancer by utilizing a substance that attacks and destroys cancer cells while leaving healthy cells alone. Without possession of such a substance, such a “cure” is illusory, and there is no meaningful possession of the method.
***
What the inventors did not do, however, is succeed in taking the last, critical step of actually isolating such a compound, or at least of developing a process through which one skilled in the art would be directly led to such a compound. Absent that step, their discoveries, valuable though they might have been, did not blossom into a full-fledged, complete invention. Scientific discoveries, and theories based on those discoveries, frequently lay the groundwork for later inventions, but that does not make the discoverer the inventor as well.
Attention is also directed to the decision in Ariad Pharmaceuticals Inc. v. Eli Lilly & Co.
(Fed. Cir. 2010) 94 USPQ2d 1161, 1175, which teaches:
In accordance with Rochester, the ?516 patent must adequately describe the claimed methods for reducing NF-?B activity, including adequate description of the molecules that Ariad admits are necessary to perform the methods. (Emphasis added)
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-26 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.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim(s) 1-26 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0256924 A1 (Vogelstein et al.) in view of US 2011/0183320 A1 (Flusberg et al.), US 2021/0054436 A1 (Lam et al.) and US 2019/0002971 A1 (Koslover et al.).
Vogelstein et al., at paragraph [0554], teach:
[0554] In some embodiments, detection of a genetic biomarker (e.g., one or more genetic biomarkers) can include any of the variety of methods described in P.C.T. Publication No. WO 2016/130704, which is hereby incorporated by reference in its entirety. For example, detection of a genetic biomarker can include to methods and compositions relating to evaluating components of a single cell preserved or embedded or contained within a contiguity preserving elements(CE). In one aspect are methods for analyzing plurality of analyte types from a single cell. In some embodiments, a plurality of contiguity preserving elements (CE) are provided, each CE comprises a single cell. The cells are lysed within the CE such that the plurality of analytes within the single cell are released within the CE. In some embodiments, plurality of types of reporter moieties are provided such that each type of reporter moiety is specific for each type of analyte. In some embodiments, the reporter moiety identify a single cell. The plurality of analytes are modified such that each type of analyte comprise a reporter moiety specific for the analyte type. In some embodiments, the CE comprising the analytes comprising said reporter moieties are combined. In some embodiments, the combined CE comprising the analytes comprising said reporter moieties are compartmentalized. In some embodiments, additional reporter moieties are provided and combined with the analytes comprising analytes such that the analytes comprise two or more different reporter moieties. The analytes comprising the reporter moieties are analyzed such that the identity of the analyte is detected and the reporter moiety identifies the source of the analyte from a single cell. In some embodiments, the exemplary plurality of analytes include but are not limited to DNA, RNA, cDNA, protein, lipids, carbohydrates, cellular organelles, (e.g., nucleus, Golgi apparatus, ribosomes, mitochondria, endoplasmic reticulum, chloroplast, cell membrane, etc.), cellular metabolites, tissue sections, cells, single cell, contents from cells or from a single cell, nucleic acid isolated from cells or from a single cell, or nucleic acid isolated from cells or from a single cell and further modified, or cell free DNA (e.g., from placental fluid or plasma). In some embodiments, the plurality of analytes include genomic DNA and mRNA. (Emphasis added)
Vogelstein et al., at paragraph [0763], teach:
Non-limiting examples of methods of detecting a nucleic acid in a sample include: PCR, RT-PCR, sequencing (e.g., next generation sequencing methods, deep sequencing), a DNA microarray, a microRNA microarray, a SNP microarray, fluorescent in situ hybridization (FISH), restriction fragment length polymorphism (RFLP), gel electrophoresis, Northern blot analysis, Southern blot analysis, chromogenic in situ hybridization (CISH), chromatin immunoprecipitation (ChIP), SNP genotyping, and DNA methylation assay. See, e.g., Meldrum et al. (2011) Clin. Biochem. Rev. 32(4): 177-195; Sidranksy (1997) Science 278(5340): 1054-9.
The above showing is deemed to fairly suggest limitations of claims
While Vogelstein et al., teaches methods of detecting different nucleic acids, and suggests RNA, Vogelstein et al., has not been found to teach detection of different types of RNA.
Vogelstein et al., has also not been found to teach of “label regions”, much less the lengths of same.
Flusberg et al., at paragraph [0061], teach:
[0061] Although certain embodiments of the invention are described in terms of detection of modified nucleotides or other modifications in a single-stranded DNA molecule (e.g., a single-stranded template DNA), various aspects of the invention are applicable to many different types of nucleic acids, including e.g., single- and double-stranded nucleic acids that may comprise DNA (e.g., genomic DNA, mitochondrial DNA, viral DNA, etc.), RNA (e.g., mRNA, siRNA, microRNA, rRNA, tRNA, snRNA, ribozymes, etc.)… (Emphasis added)
Lam et al., at paragraph [0227], teach:
[0227] In some embodiments, the label region 314 can include a barcode sequence or a molecular label 318 and a cell label 320. In some embodiments, the label region 314 can include one or more of a universal label, a dimension label, and a cell label. The barcode sequence or molecular label 318 can be, can be about, can be at least, or can be at most, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, or a number or a range between any of these values, of nucleotides in length.
The above showing is deemed to fairly suggest limitations of clams 1-22.
Neither Vogelstein et al., Flusberg et al., nor Lam et al., have been found to teach using combinations of optical labels.
Koslover et al., teaches using combination of “optical labels” in assays directed to determining presence of polymers such as polynucleotides.
Koslover et al., in paragraph [0006], teach:
each polymer having one or more optical labels attached thereto capable of generating an optical signal having at least a first wavelength indicative of a characteristic of the polymer; (c) exciting with an excitation beam having a second wavelength the optical labels of the polymers as they translocate through the signal generation regions of the apertures, wherein the optical labels in the detection regions generate optical signals whose first wavelength is different than the second wavelength; and (d) detecting optical signals from the optical labels in the signal generation regions to determine the characteristics of the polymers. (Emphasis added)
The aspect of using different combination of labels is deemed to fairly suggest limitations of claims 23-26.
In view of the above presentation it would have been obvious to one of ordinary skill in the art at the time of the invention to have devised a method of Vogelstein et al., for detection of not just RNA, but different types of RNA as identified by Flusberg et al., and to have devised probes having the lengths of probes described by Lam et al., and to have enhanced the fluorescent probes of Vogelstein et al., whereby they comprise the optical labels as disclosed by Koslover et al.
In view of the well developed state of the art and the significant interest in one being able to detect a variety of RNA molecules, said ordinary artisan would have been amply motivated and would have has a most reasonable expectation of success.
In view of the above presentation ad in the absence of convincing evidence to the contrary, claims 1-26 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0256924 A1 (Vogelstein et al.) in view of US 2011/0183320 A1 (Flusberg et al.), US 2021/0054436 A1 (Lam et al.) and US 2019/0002971 A1 (Koslover et al.).
Conclusion
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
1 Attention is directed to 37 CFR 1.57(d), which sates in part:
(d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. "Essential material" is material that is necessary to:
(1) Provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a);
(2) Describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or
(3) Describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f). (Emphasis added)
(e) Other material ("Nonessential material") may be incorporated by reference to U.S. patents, U.S. patent application publications, foreign patents, foreign published applications, prior and concurrently filed commonly owned U.S. applications, or non-patent publications. An incorporation by reference by hyperlink or other form of browser executable code is not permitted.