DETAILED ACTION
Prosecution Reopened
In view of the appeal brief filed on 11 August 2025, PROSECUTION IS HEREBY REOPENED. New grounds of rejection are set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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 .
Claims 1, 2, 8, 11, 21, 27-29, 44, 50, 55-59, and 61 are pending and under examination.
Drawings
The drawings were received on 21 February 2024. 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, 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.
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 [25 USPQ2d 1601] (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
***
In Fiers, we rejected the argument that “only similar language in the specification or original claim is necessary to satisfy the written description requirement.” 984 F.2d at 1170 (emphasis added). Rather, we held that original claim language to “a DNA coding for interferon activity” failed to provide an adequate written description as it amounted to no more than a “wish” or “plan” for obtaining the claimed DNA rather than a description of the DNA itself. Id. at 1170-71. That Fiers applied § 112, first paragraph, during an interference is irrelevant for, as we stated above, the statute contains no basis for ignoring the description requirement outside of this context. And again in Enzo we held that generic claim language appearing in ipsis verbis in the original specification does not satisfy the written description requirement if it fails to support the scope of the genus claimed. 323 F.3d at 968. We concluded that “[a] claim does not become more descriptive by its repetition, or its longevity.” Id. at 969.
***
The written description requirement also ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function—a problem that is particularly acute in the biological arts.
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-07.2022], at part II iii):
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 applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. (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.
Holding and Rationale.
Claims 1, 2, 8, 11, 21, 27-29, 44, 50, 55-59, and 61 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In applying the guidance as set forth in the Guidelines, including the decisions in Fiers and Lilly, it is noted that applicant is claiming “method for detecting a target nucleic acid in a plurality of samples” (claims 1, 8, 11, 21, 27-29, 44, 50 and 61), and “method of detecting target nucleic acids in a plurality of samples” (claims 2, and 55-59). Said methods are deemed to encompass the detection of any and all manner of nucleic acids as found in any and all manner of organisms through the use of “a primary affinity reagent, wherein the primary affinity reagent is an oligonucleotide between 10 to 1000 nucleotides in length, and wherein the primary affinity reagent hybridizes to the target nucleic acid in the sample”.
The nucleotide sequences of i) the target in the sample, ii) the “primary affinity reagent”, and iii) the nucleotide sequence of the “capture reagent” are deemed to be essential material.1
While an applicant is not required to teach each and every possible embodiment encompassed by the claims, the specification still must provide a full, clear, and concise description of the genus encompassed by the claims so that one would be readily able to determine if a species fell within the claims’ scope, and to also reasonably suggest that applicant had possession of the invention at the time of filing. In support of this position, attention is directed to the decision in In re Shokal, 113 USPQ 283 (CCPA 1957) wherein is stated:
It appears to be well settled that a single species can rarely, if ever, afford sufficient support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.2d 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of small genus such as the halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably larger number of reductions to practice would probably be necessary.
***
We are of the opinion that a genus containing such a large number of species cannot properly be identified by the mere recitation or reduction to practice of four or five of them. As was pointed out by the examiner, four species might be held to support a genus, if such genus is disclosed in clear language; but where those species must be relied on not only to illustrate the genus but to define what it is, the situation is otherwise.
In the present case, a review of the disclosure does locate a Sequence Listing. The Sequence Listing comprises some 61 nucleic acid sequences all of which are labeled as being both DNA and a Synthetic and Artificial Sequence and all of which are 35 nucleotides in length. In short, the disclosure has not been found to disclose any DNA or RNA, that occurs in any life form, id est., a target. Likewise, the Sequence Listing has not been found to comprise any oligonucleotides, be it DNA or RNA, that range in size from 10-1000 nucleotides in length and which would serve as the “primary affinity reagent” or the “capture reagent”. In this regard, the specification does not provide any written description regarding what molecular structures are required for an oligonucleotide between 10 to 1000 nucleotides to perform the function of an “affinity agent” or a “capture reagent”.
Attention is directed to the decision of Vas-Cath Inc. v. Mahurkar 19 USPQ2d 1111 (CAFC, 1991):
This court in Wilder (and the CCPA before it) clearly recognized, and we hereby reaffirm, that 35 USC 112, first paragraph, requires a “written description of the invention” which is separate and distinct from the enablement requirement. The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the “applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
It appears that applicant is attempting to satisfy the written description requirement of 35 USC 112, first paragraph, through obviousness. Obviousness, however, cannot be relied upon for satisfaction of the written description requirement. In support of this position, attention is directed to the decision in University of California v. Eli Lilly and Co. (Fed. Cir. 1997) 43 USPQ2d at 1405, citing Lockwood v. American Airlines Inc. (Fed. Cir. 1997) 41 USPQ2d at 1966:
Recently, we held that a description which renders obvious a claimed invention is not sufficient to satisfy the written description requirement of that invention.
For the above reasons and in the absence of convincing evidence to the contrary, the disclosure has not been found to satisfy the requirements as set forth in the en banc decision in Ariad, nor provide the “representative number of species falling within the scope of the genus” as reiterated in Sanofi. Accordingly, claims 1, 2, 8, 11, 21, 27-29, 44, 50, 55-59, and 61 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.
Response to argument
At pages 19-28 of the Appeal Brief applicant’s representative traverses the rejection of claims under 35 USC 112 for not satisfying the written description requirement.
At page 22 of the Brief said representative asserts:
The Office’s rejection is in error because the “target nucleic acid” or “reagent” need not be disclosed to satisfy the written description requirement. (Emphasis in original)
Appellant respectfully submits that the Office has erred in interpreting the recited “target nucleic acid” and “target nucleic acids” as subject to the disclosure requirement of Ariad or Sanofi, and that particular targets and reagents do not need to be disclosed to satisfy the written description requirement.
The above argument has been considered and has not been found persuasive.
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.
***
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 the present case the methods are deemed to encompass the detection of any and all manner of nucleic acids as found in any and all manner of organisms through the use of “a primary affinity reagent”.
In further support of this interpretation of the claims attention is directed to paragraph [0011] of the disclosure. As asserted to by applicant:
Thus, the present disclosure is not intended to be limited to the embodiments
presented, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein. (Emphasis added)
The nucleotide sequences of i) the target in the sample, ii) the “primary affinity reagent”, and iii) the nucleotide sequence of the “capture reagent” are deemed to be essential material. The claimed methods are deemed to encompass “target nucleic acid” that were known, that which has become known subsequent to filing, as well as those nucleic acids that will become known at some point in the future. A review of the disclosure does identify a Sequence Listing. Said Sequence Listing comprises some 61 DNA sequences, all of which are 35 nucleotides in length and are all identified as being an “Artificial Sequence”. As can be seen in each of the two independent claims, claims 1 and 2, the method encompasses virtually any target nucleic acid and ID barcodes that are to range “between 10 to 1000 nucleotides”. As evidenced above, the disclosure does not provide any example of such a range of oligonucleotides, much less a representative number of sequences that have utility. Additionally, the disclosure has not been found to disclose the nucleotide sequence that if found in “an[y] organism, such as an animal or human”, much less those sequences that have utility under 35 USC 101. Such non-disclosure by applicant has not been found to provide evidence that applicant, as of the effective filing date, was in possession of the full genus of “target nucleic acids”. Such nondisclosure has not been found to satisfy the written description requirements of 35 USC 112. In further support of this position it is noted that the complete sequence of the human Y chromosome was not determined until 2022, which is some 2 years post the effective filing date of the instant application (June 19, 2020). In support of this position attention is directed to Rhie et al., “The complete sequence of a human Y chromosome”, Nature, Vol. 621, 14 September 2023. Clearly, applicant was not in possession of that which was not yet known but encompassed by the claims.
At page 24 of the Brief appellant asserts:
The instant claims are similar to those at issue in Terbrueggen-2, Oliver, Lindstrom, and Zhang because the instant claims are directed to “platform technology” (i.e., a platform) that can detect any number of nucleic acids by hybridizing oligonucleotides. Even though no specific nucleic acids are recited in claim 1 or claim 2, the instant claims satisfy the written description requirement because specific nucleic acid sequences are not the invention.
The above argument has been considered and has not been found persuasive. As evidenced above, the claimed method encompasses “any number of nucleic acids”, which has been construed as encompassing that which was not known as of the effective priority date, which, as shown above, encompasses the human Y chromosome, which was not sequenced until 2022, which is some two years subsequent to applicant’s priority date. Clearly, applicant was not in possession of this aspect of the claimed method.
While the claims are to a method and not to a composition, it is well settled that an applicant must provide an adequate written description of those species of “a primary affinity reagent” encompassed by the claimed method. Applicant’s non-disclosure of even one sequence that occurs in any organism has not been found to support the position that applicant, as of the effective filing date, or even the filing date, was in possession of the full scope of the claimed method.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
At page 26 of the Brief applicant’s representative asserts:
The Summary of the Claimed Subject Matter in Section III, at pages 1-4, provides a detailed identification of exemplary support in the specification as filed for each limitation of independent claims 1 and 2, and is incorporated herein by reference.
As discussed there and elsewhere above and throughout this brief, the appealed claims are directed to a method of detecting target nucleic acids by hybridization of oligonucleotides to their complementary sequences. The claims recite a primary affinity reagent that is an oligonucleotide of a specific length. This primary affinity reagent hybridizes to a target nucleic acid in a sample.
As to the “reagents,” and as detailed in the Summary of the Claimed Subject Matter, an ID reagent is added to the sample in both claims 1 and 2. In claim 1, the ID reagent comprises an ID barcode and a capture reagent. The ID barcode is an oligonucleotide between 10 to 1000 nucleotides in length, and wherein each ID barcode identifies a sample in the plurality of samples. The capture reagent is an oligonucleotide between 10 to 1000 nucleotides in length, and wherein the capture reagent hybridizes to a target nucleic acid or to a primary affinity reagent.
The above arguments have been considered and have not been found persuasive towards the withdrawal of the rejection. While the claims do require the use of a “primary affinity reagent [that] is an oligonucleotide between 10 to 1000 nucleotides in length, and wherein the primary affinity reagent hybridizes the target nucleic acid”, the disclosure does not provide the nucleotide sequence for any oligonucleotide that is complementary to any target sequence found in any organism. In support of this position and as noted above, the disclosure does comprise a Sequence Listing that comprises 61 oligonucleotides that are but 35 nucleotides in length, and every one of which is identified as being an “Artificial Sequence”. It stands to reason that if every sequence is an “Artificial Sequence” they would not bind to any sequence found in any organism. Clearly, applicant’s disclosure of oligonucleotides that are 35 nucleotides in length does not support the position that applicant, as of the effective filing date, was in possession of primary affinity reagents that span the entire range of “10 to 1000 nucleotides in length”.
At page 27 of the brief applicant’s representative asserts:
In particular, Applicant submits that, using the principles of hybridization, and in view of the explicit identification in the specification of oligonucleotides from at least 10 and up to 1000 nucleotides (see, e.g., paragraph [0026]), a person of skill in the art would understand that oligonucleotides from 10 to 1000 nucleotides in length could be used, and would not believe that the invention was limited to the exemplary 35 nucleotide long probes of Example 1, as seemingly suggested by the Office.
While agreement is reached in that “a person of skill in the art would understand that oligonucleotides from 10 to 1000 nucleotides in length could be used”, applicant’s nondisclosure of any sequence from 10 to 1000 nucleotides that is complementary to any sequence in any organism, much less sequences found in any organism which has utility under 35 USC 101, including SARS-COVID-2 (claim 11), does not support the argument that applicant was in possession of the genus of “primary affinity reagents” that would hybridize to any sequence that is present in the genome of any organism, including the human Y chromosome that was not sequenced until 2 years post effective filing date.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1, 2, 8, 11, 21, 27-29, 44, 50, 55-59, and 61 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 § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Zhao et al. (2015) teach that
The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented” (See Abstract)
Zhao et al. (2015), at page 152, left column, teach:
To distinguish different binding events in parallel, molecules should be encoded. [ 5–8 ] The most common approach is to use a planar array, such as a nucleic acid and protein microarray, in which the probe molecules are immobilized on a substrate and encoded by the coordinate of their positions, as illustrated in Figure 1a.
In comparison, suspension arrays that use barcode particles as microcarriers for the probes’ attachment and reactions (Figure 1 b) became an attractive alternative as a multiplex assay. They can offer higher flexibility for detecting new analytes and show faster reaction kinetics in solution because of the radial diffusion of analytes or probes.
In this paper, we present studies dealing with the microfluidic synthesis of barcode particles for multiplex assays.
Zhao et al. (2015), at page 163, left column, first full paragraph, teach:
The microfluidic FL was first used for synthesizing barcode particles by Doyle and coworkers. [ 146–148 ] In their system, two monomer laminar streams flowed adjacently through a microfluidic channel, one stream with fluorescent-labeled PEG monomers served to generate the graphical code and the other contained PEG monomers with the oligonucleotide probe that was used to detect the analyte of interest.
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Figure 3. (a) Schematic illustration the DNA dendrimer fluorescent barcode labels by fluorescence intensity ratio; (b) DNA nanobarcode, DNA target and polystyrene microbeads form sandwich structure in multiplex detection, scale bar is 5 μm; (c–e) Illustration of RNA nanostring encoded assays: (c) complex structures formed after hybridization of a target mRNA, its specific reporter and capture probes; (d) schematic representation of binding, electrophoresis, and immobilization: i) the purified complexes are attached to a streptavidin-coated slide via biotinylated capture probes, ii) voltage is applied to elongate and align the molecules, iii) the stretched reporters are immobilized; (e) the reporter barcodes are imaged with a fluorescence microscope equipped with high resolution and magnification lens. (Emphasis added)
In view of the above showing, the method of claim 1 is deemed to be fairly disclosed. Accordingly, claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
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.
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.
Standard for Obviousness.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Attention is directed to In re Jung, 98 USPQ2d 1174, 1178 (Fed. Cir. 2011) wherein is stated:
There has never been a requirement for an examiner to make an on-the-record claim construction of every term in every rejected claim and to explain every possible difference between the prior art and the claimed invention in order to make out a prima facie rejection. This court declines to create such a burdensome and unnecessary requirement. “[Section 132] does not mandate that in order to establish prima facie anticipation, the PTO must explicitly preempt every possible response to a section 102 rejection. Section 132 merely ensures that an applicant at least be informed of the broad statutory basis for the rejection of his claims, so that he may determine what the issues are on which he can or should produce evidence.” Chester, 906 F.2d at 1578 (internal citation omitted). As discussed above, all that is required of the office to meet its prima facie burden of production is to set forth the statutory basis of the rejection and the reference or references relied upon in a sufficiently articulate and informative manner as to meet the notice requirement of § 132. As the statute itself instructs, the examiner must “notify the applicant,” “stating the reasons for such rejection,” “together with such information and references as may be useful in judging the propriety of continuing prosecution of his application.” 35 U.S.C. § 132.
Attention is directed to the decision in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007):
When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
It is further noted that prior art is not limited to the four corners of the documentary prior art being applied. Prior art includes both the specialized understanding of one of ordinary skill in the art, and the common understanding of the layman. It includes “background knowledge possessed by a person having ordinary skill in the art. . . [A] court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1396.
Suggestion, teaching or motivation does not have to be explicit and “may be found in any number of sources, including common knowledge, the prior art as a whole or the nature of the problem itself’” Pfizer, Inc. v. Apotex, Inc. 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) citing Dystar Textilfarben GMBH v. C. H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006).
Holding and Rationale
Claim(s) 1, 2, 8, 21, 27-29, 44, 50, 55-59, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20) in view of Cai et al. (US 2014/0031243, Publication of US application 13/725,717) and Zhang et al. (2018) (Zhang et al., Ratiometric Fluorescence Coding for Multiplex Nucleic Acid Amplification Testing, Anal Chem., 2018 Oct 16;90(20):12180-12186. doi: 10.1021/acs.analchem.8b03266. Epub 2018 Oct 5).
Zhao et al. (2015) teach that
The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented” (See Abstract)
Zhao et al. (2015), at page 152, left column, teach:
To distinguish different binding events in parallel, molecules should be encoded. [ 5–8 ] The most common approach is to use a planar array, such as a nucleic acid and protein microarray, in which the probe molecules are immobilized on a substrate and encoded by the coordinate of their positions, as illustrated in Figure 1a.
In comparison, suspension arrays that use barcode particles as microcarriers for the probes’ attachment and reactions (Figure 1 b) became an attractive alternative as a multiplex assay. They can offer higher flexibility for detecting new analytes and show faster reaction kinetics in solution because of the radial diffusion of analytes or probes.
In this paper, we present studies dealing with the microfluidic synthesis of barcode particles for multiplex assays.
Zhao et al. (2015), at page 163, left column, first full paragraph, teach:
The microfluidic FL was first used for synthesizing barcode particles by Doyle and coworkers. [ 146–148 ] In their system, two monomer laminar streams flowed adjacently through a microfluidic channel, one stream with fluorescent-labeled PEG monomers served to generate the graphical code and the other contained PEG monomers with the oligonucleotide probe that was used to detect the analyte of interest.
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Figure 3. (a) Schematic illustration the DNA dendrimer fluorescent barcode labels by fluorescence intensity ratio; (b) DNA nanobarcode, DNA target and polystyrene microbeads form sandwich structure in multiplex detection, scale bar is 5 μm; (c–e) Illustration of RNA nanostring encoded assays: (c) complex structures formed after hybridization of a target mRNA, its specific reporter and capture probes; (d) schematic representation of binding, electrophoresis, and immobilization: i) the purified complexes are attached to a streptavidin-coated slide via biotinylated capture probes, ii) voltage is applied to elongate and align the molecules, iii) the stretched reporters are immobilized; (e) the reporter barcodes are imaged with a fluorescence microscope equipped with high resolution and magnification lens. (Emphasis added)
Cai et al. (US 2014/0031243) teach in their abstract:
Methods and systems are provided for creating molecular barcodes or indicia for cellular constituents within single cells and for resolving such barcodes or indicia with super resolution technologies such as super-resolution microscopy. By this approach, numerous molecular species that can be measured simultaneously in single cells. It has been demonstrated that multiple mRNA transcripts can be labeled with a spatially ordered sequence of fluorophores, and that barcodes can be resolved. In addition, alternative splicing events can be characterized by identifying and quantifying mRNA isoforms in an individual cell.
Zhang et al. teaches that “Although nucleic acid amplification testing (NAAT) has become the cornerstone for molecular diagnosis of diseases, expanding the multiplexed detection capacity of NAAT remains an important objective. To this end, encoding each nucleic acid target with a specific fluorescently labeled probe has been the most mature approach for multiplexed
detection. Unfortunately, the number of targets that can be differentiated via this one-target-one-fluorophore multiplexed detection approach is restricted by spectral overlaps between fluorophores. In response, we present herein a new multiplexed detection approach termed ratiometric fluorescence coding, in which we encode each nucleic acid target with a specific ratio between two standard fluorophores. In ratiometric fluorescence coding, we employ the padlock
probe chemistry to encode each nucleic acid target with a specific number of binding sites for two probes labeled with different fluorophores. Coupling the padlock probes with either rolling circle amplification (RCA) or hyperbranched rolling circle amplification (HRCA), we transform each nucleic acid target into a specific template that allows hybridization with the fluorescently labeled probes at predesigned ratios, thereby achieving multiplexed detection. For demonstration, we detected DNA targets from six infectious diseases and demonstrated the potential for further expanding the multiplexing capability of our approach. With further development, ratiometric fluorescence coding has the potential to enable highly multiplexed detection of nucleic acid targets and facilitate molecular diagnosis of diseases” (See Abstract).
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In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art at the time of the invention to have modified the method of Zhao et al. (2015) whereby one is able to detect multiple target sequences, including the simultaneous detection of “multiple mRNA transcripts”. Given such, and in the absence of convincing evidence to the contrary, claims 1, 2, 8, 21, 27-29, 44, 50, 55-59, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20) in view of Cai et al. (US 2014/0031243, Publication of US application 13/725,717) and Zhang et al. (2018) (Zhang et al., Ratiometric Fluorescence Coding for Multiplex Nucleic Acid Amplification Testing, Anal Chem., 2018 Oct 16;90(20):12180-12186. doi: 10.1021/acs.analchem.8b03266. Epub 2018 Oct 5).
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20) in view of Cai et al. (US 2014/0031243, Publication of US application 13/725,717) and Zhang et al. (2018) (Zhang et al., Ratiometric Fluorescence Coding for Multiplex Nucleic Acid Amplification Testing, Anal Chem., 2018 Oct 16;90(20):12180-12186. doi: 10.1021/acs.analchem.8b03266. Epub 2018 Oct 5) as applied to claims 1, 2, 8, 21, 27-29, 44, 50, 55-59, and 61 above, and further in view of WO 2017/070429 A1 (Osborn et al.)
As evidenced above in paragraph 61, Zhao et al. (2015), teaches using probes so to detect the analyte of interest. Zhao et al. (2015), however, have not been found to disclose SARS-CoV2, which is also recognized as being SARS-COVID-2. (In support of the position that the virus is recognized by a plurality of names, attention is directed to page 34, paragraphs [0125] and [0126], of the instant application.)
Osborn et al., at page 19, first paragraph, teach of “severe acute respiratory syndrome coronavirus (SARS-CoVl, SARS-CoV2, and SARS-CoV3)”.
In view of the art having advanced so recognize such viruses, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of Zao et al., Cai et al., and Osborn et al., whereby the method would allow for the detection of additional, medially significant viruses.
In view of the above analysis and in the absence of convincing evidence to the contrary, claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20) in view of Cai et al. (US 2014/0031243, Publication of US application 13/725,717) and Zhang et al. (2018) (Zhang et al., Ratiometric Fluorescence Coding for Multiplex Nucleic Acid Amplification Testing, Anal Chem., 2018 Oct 16;90(20):12180-12186. doi: 10.1021/acs.analchem.8b03266. Epub 2018 Oct 5) as applied to claims 1, 2, 8, 21, 27-29, 44, 50, 55-59, and 61 above, and further in view of WO 2017/070429 A1 (Osborn et al.)
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,266,876 in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Although the claims at issue are not identical, they are not patentably distinct from each other because both methods are directed to detecting any of a variety of nucleic acids through the use of barcodes.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 10,457,980 B2 (Appl. No. 14/435,735) in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Claim 1 of US 10,457,980 B2:
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Zhao et al. (2015) teach that
The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented” (See Abstract)
Zhao et al. (2015), at page 152, left column, teach:
To distinguish different binding events in parallel, molecules should be encoded. [ 5–8 ] The most common approach is to use a planar array, such as a nucleic acid and protein microarray, in which the probe molecules are immobilized on a substrate and encoded by the coordinate of their positions, as illustrated in Figure 1a.
In comparison, suspension arrays that use barcode particles as microcarriers for the probes’ attachment and reactions (Figure 1 b) became an attractive alternative as a multiplex assay. They can offer higher flexibility for detecting new analytes and show faster reaction kinetics in solution because of the radial diffusion of analytes or probes.
In this paper, we present studies dealing with the microfluidic synthesis of barcode particles for multiplex assays.
Zhao et al. (2015), at page 163, left column, first full paragraph, teach:
The microfluidic FL was first used for synthesizing barcode particles by Doyle and coworkers. [ 146–148 ] In their system, two monomer laminar streams flowed adjacently through a microfluidic channel, one stream with fluorescent-labeled PEG monomers served to generate the graphical code and the other contained PEG monomers with the oligonucleotide probe that was used to detect the analyte of interest.
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Figure 3. (a) Schematic illustration the DNA dendrimer fluorescent barcode labels by fluorescence intensity ratio; (b) DNA nanobarcode, DNA target and polystyrene microbeads form sandwich structure in multiplex detection, scale bar is 5 μm; (c–e) Illustration of RNA nanostring encoded assays: (c) complex structures formed after hybridization of a target mRNA, its specific reporter and capture probes; (d) schematic representation of binding, electrophoresis, and immobilization: i) the purified complexes are attached to a streptavidin-coated slide via biotinylated capture probes, ii) voltage is applied to elongate and align the molecules, iii) the stretched reporters are immobilized; (e) the reporter barcodes are imaged with a fluorescence microscope equipped with high resolution and magnification lens. (Emphasis added)
As evidenced above, US 10,457,980 B2 teaches performing nucleic acid hybridization assay wherein one incorporates “unique molecular barcode for each unique nucleic acid in a plurality of nucleic acid molecules in a sample”. As disclosed therein, one provides multiple probes, each labeled with a different label.
Zhao et al. (2015) teaches development and use of oligonucleotide probes that are attached to particles that also comprise barcoded oligonucleotides which in turn can serve as the detectable label.
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 detectable probes, wherein the means of detection can comprise barcoded oligonucleotides which, along with the probe, are bound to particles. In view of the well developed state of the art and detailed guidance, said ordinary artisan would have been amply motivated and would have had a most reasonable expectation of success.
In view of the above presentation and in the absence of convincing evidence to the contrary, claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 10,457,980 B2 (Appl. No. 14/435,735) in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US 11,473,129 (Appl. No. 16/572,511) in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Claim 1 of US 11,473,129:
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Zhao et al. (2015) teach that
The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented” (See Abstract)
Zhao et al. (2015), at page 152, left column, teach:
To distinguish different binding events in parallel, molecules should be encoded. [ 5–8 ] The most common approach is to use a planar array, such as a nucleic acid and protein microarray, in which the probe molecules are immobilized on a substrate and encoded by the coordinate of their positions, as illustrated in Figure 1a.
In comparison, suspension arrays that use barcode particles as microcarriers for the probes’ attachment and reactions (Figure 1 b) became an attractive alternative as a multiplex assay. They can offer higher flexibility for detecting new analytes and show faster reaction kinetics in solution because of the radial diffusion of analytes or probes.
In this paper, we present studies dealing with the microfluidic synthesis of barcode particles for multiplex assays.
Zhao et al. (2015), at page 163, left column, first full paragraph, teach:
The microfluidic FL was first used for synthesizing barcode particles by Doyle and coworkers. [ 146–148 ] In their system, two monomer laminar streams flowed adjacently through a microfluidic channel, one stream with fluorescent-labeled PEG monomers served to generate the graphical code and the other contained PEG monomers with the oligonucleotide probe that was used to detect the analyte of interest.
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Figure 3. (a) Schematic illustration the DNA dendrimer fluorescent barcode labels by fluorescence intensity ratio; (b) DNA nanobarcode, DNA target and polystyrene microbeads form sandwich structure in multiplex detection, scale bar is 5 μm; (c–e) Illustration of RNA nanostring encoded assays: (c) complex structures formed after hybridization of a target mRNA, its specific reporter and capture probes; (d) schematic representation of binding, electrophoresis, and immobilization: i) the purified complexes are attached to a streptavidin-coated slide via biotinylated capture probes, ii) voltage is applied to elongate and align the molecules, iii) the stretched reporters are immobilized; (e) the reporter barcodes are imaged with a fluorescence microscope equipped with high resolution and magnification lens. (Emphasis added)
As evidenced above, US 11,473,129 B2 teaches and claims a method whereby multiple target nucleic acids are detected through the use of oligonucleotides that comprise a barcode and wherein the barcode is unique to the target.
As evidenced above, Zhao et al. (2015) teach performing multiplexed assay where barcoded oligonucleotides are used to identify probes and their targets.
In view of the well-developed state of the art and detailed guidance, said ordinary artisan would have been amply motivated and would have had a most reasonable expectation of success.
In view of the above presentation and in the absence of convincing evidence to the contrary, claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US 11,473,129 (Appl. No. 16/572,511) in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of copending Application No. 18/723,184 in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
This is a provisional nonstatutory double patenting rejection.
Claim 3 of application 18/723,184 is reproduced below.
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Zhao et al. (2015) teach that
The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented” (See Abstract)
Zhao et al. (2015), at page 152, left column, teach:
To distinguish different binding events in parallel, molecules should be encoded. [ 5–8 ] The most common approach is to use a planar array, such as a nucleic acid and protein microarray, in which the probe molecules are immobilized on a substrate and encoded by the coordinate of their positions, as illustrated in Figure 1a.
In comparison, suspension arrays that use barcode particles as microcarriers for the probes’ attachment and reactions (Figure 1 b) became an attractive alternative as a multiplex assay. They can offer higher flexibility for detecting new analytes and show faster reaction kinetics in solution because of the radial diffusion of analytes or probes.
In this paper, we present studies dealing with the microfluidic synthesis of barcode particles for multiplex assays.
Zhao et al. (2015), at page 163, left column, first full paragraph, teach:
The microfluidic FL was first used for synthesizing barcode particles by Doyle and coworkers. [ 146–148 ] In their system, two monomer laminar streams flowed adjacently through a microfluidic channel, one stream with fluorescent-labeled PEG monomers served to generate the graphical code and the other contained PEG monomers with the oligonucleotide probe that was used to detect the analyte of interest.
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Figure 3. (a) Schematic illustration the DNA dendrimer fluorescent barcode labels by fluorescence intensity ratio; (b) DNA nanobarcode, DNA target and polystyrene microbeads form sandwich structure in multiplex detection, scale bar is 5 μm; (c–e) Illustration of RNA nanostring encoded assays: (c) complex structures formed after hybridization of a target mRNA, its specific reporter and capture probes; (d) schematic representation of binding, electrophoresis, and immobilization: i) the purified complexes are attached to a streptavidin-coated slide via biotinylated capture probes, ii) voltage is applied to elongate and align the molecules, iii) the stretched reporters are immobilized; (e) the reporter barcodes are imaged with a fluorescence microscope equipped with high resolution and magnification lens. (Emphasis added)
As evidenced above, claim 3 of 18/723,184 is drawn to a method of reducing background in a method to reduce background signal of probes bound to targets. As seen therein, one is using multiple probes (primary, secondary, tertiary, quaternary and readout) where specified probes bind to targets and other specified probes bind to other probes. Such is deemed to be analogous to the “primary affinity reagent” oligonucleotide and the “ID barcode” oligonucleotides of claim 1 of the instant application.
As evidenced above, Zhao et al. (2015) “present studies dealing with the microfluidic synthesis of barcode particles for multiplex assays”.
In view of the above presentation, the claimed method of “detecting a target nucleic acid in a plurality of samples” is deemed to be obvious in view of claim 3 of 18/723,184 and Zhao et al. (2015). Accordingly, claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of copending Application No. 18/723,184 in view of Zhao et al. (2015) (Zhao et al., Microfluidic synthesis of barcode particles for multiplex assays, Small, 2015 Jan 14;11(2):151-74. doi: 10.1002/smll.201401600. Epub 2014 Oct 20).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
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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.