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 .
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).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). 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)
Claim Objections
Claim 20 is objected to because of the following informalities: As a result of amendment the claim recites the limitation of “dithiothreitol (DDT)”. DDT is recognized as being the abbreviation for the pesticide dichlorodiphenyltrichloroethane1. It is recognized that DTT is the common abbreviation for dithiothreitol.2 Appropriate correction is required.
Claim Rejections - 35 USC § 112, Second Paragraph / (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
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-01.2024]:
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 [R-01-2024], 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).
Holding and Rationale
Claims 1-11, 18-20, 23-24, 33, and 40 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.
Independent claims 1, 23, and 33 are indefinite with respect to what constitutes the metes and bounds of Jβ1, Jβ2, Cβ1 and Cβ2. Acknowledgement is made of the target being a “T cell receptor (TCR) β1”, “Cβ1 of the TCRβ1 mRNA”, “Jβ2 of the TCRβ2 mRNA”, and “Cβ2 of the TCRβ2 mRNA” and that T cells and T cell receptors occur in mammals, of which there are some 6,400 extant species.3, 4 Given such, it is less than clear as to just which mammalian specie(s) is/are the source of the different T cell receptors.
Claims 1, 23, and 33 are indefinite with respect to what lengths and any secondary structures, if any of the ”T section[s]” and “L section[s]” of the different target probes have/encompass.
Claims 2-11 and 18-20, which depend from claim 1, fail to overcome these issues and are similarly rejected. Claim 24, which depends from claim 23, and claim 40, which depends from claim 33, fail to overcome these issues and are similarly rejected.
Claim 33 is indefinite with respect to what constitutes the metes and bounds of “a signal generating complex”.
Claim 40 is indefinite with respect to what constitutes the metes and bounds of “an amplifier, a pre-amplifier, and/or a pre-pre-amplifier”. Acknowledgement is made of the specification, at page 23, paragraph [0092], directs attention to 22017/010672 as providing “exemplary pre-pre-amplifiers”. It is noted that narrowing limitations found in the disclosure cannot be read into the claim(s). In support of this position attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Said claim 40 is also indefinite with respect to whether the clause “preferably comprises a sequence complementary to any one of SEQ ID Nos: 1-16” is a limitation.
Response to traversal
Applicant’s representative, at page 13 of the response of 23 January 2026, hereinafter the response, traverses the rejection of claims under 35 USC 112as it relates to the length of L and T sections. As is asserted to therein:
Lastly, the Examiner further asserts that "[c]laims 1, 23, and 33 are indefinite with respect to just what constitutes the metes and bounds of 'a T section' and 'an L section" (Office Action, p. 8). Based on the above legal standard, Applicant respectfully submits that "T section" and "L section," as recited in independent claims 1, 23 and 33, are not indefinite and that one of ordinary skill in the art would readily understand the meaning of these terms in the context of the present claims when read in light of the specification. For example, the present application clearly describes that each target probe comprises a "T section" that is complementary to (i.e., is capable of binding to) a portion of a target mRNA, and an "L section" as being complementary to (i.e., is capable of binding to) a portion of a signal generating complex (see, e.g., paragraphs [0074]-[0088] of the present application). Additionally, FIG. 2 clearly describes the structures of the target probes with respect to their T sections and L sections (see paragraphs [0043]-[0045], [0159], and [0162] of the present application), and FIGS. 3 and 4 clearly demonstrate the detection of TCRβ1 mRNA and TCRβ2 mRNA using this structure. Thus, in view of the knowledge in the art and the language in the specification discussed above, Applicant submits that the present application provides more than enough certainty for one of ordinary skill in the art to understand the metes and bounds of the currently amended claims with respect to use of the terms "T section" and "L section."
In view of all the foregoing, Applicant respectfully requests reconsideration and withdrawal of the rejections under 35 U.S.C. 112, second paragraph.
This argument has been fully considered and has not been found persuasive. Attention is directed to MPEP 2145 I [R-01.2024].
An argument by the applicant is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration
In view of the above analysis and in he absence of convincing evidence to the contrary, the rejection is maintained.
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.
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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.
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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-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)
Acknowledgement is made of the fact that the claims 23 and 24 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. (Emphasis added)
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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 states:
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 1-11, 18-20, 23-24, 33, and 40 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, 20, 23, 33, and 40 are deemed to be representative and, for convenience, are reproduced below.
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As evidenced above, the claims, be they to a composition (claims 1-11 and 18-20), or to a method (claims 23 and 24) or to a kit (claims 33 and 40), they each identify different mRNA targets. More specifically, claims 1, 23, and 33 identify “target T cell receptor (TCR) β1 mRNA”, “Jβ1 of the TCR β1 mRNA”, “Cβ1 of the TCR β1 mRNA”, “Jβ2 of the TCR β2 mRNA”, and “Cβ2 of the TCR2 mRNA”.
While the claims identify multiple mRNA targets, they have not limited the mammalian source of these sequences. Given such, the claims are construed to encompass equivalent sequences in any of the 1,600 known mammalian species.
A review of the disclosure does identify a Sequence Listing. Said Sequence Listing comprises 16 sequences, each of which is identified as being “DNA”, “artificial” and “synthetic”. The disclosure has not been found to provide any mRNA sequence, much less the sequence for any of the specific targets encompassed by the claims. In addition to the non-disclosure of target mRNA sequence, it is noted that claims 20 and 40 also specify that the composition (claim 20) or the kit (claim 40) also comprise tRNA. The disclosure has not been found to provide the nucleotide sequence for any RNA sequence, much less any tRNA molecule that occurs in any of the 1,600 different species of mammal.
Applicant’s nondisclosure of the nucleotide sequence for any target, much less the nucleotide sequence for the genus of tRNA molecules encompassed by the claims, has not been found to reasonably suggest that applicant was in possession of the claimed genus of methods, compositions, and kits as of the effective priority date (21 August 2020).
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-11, 18-20, 23-24, 33, and 40 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 traversal
Applicant’s representative, at pages 13-15 of the response, traverse the rejection of claims under 35 USC 112 for not satisfying the written description requirement. At page 14 of the response said representative asserts:
Applicant respectfully disagrees with these rejections and directs the Examiner's attention to paragraph [0162] and Table 1 of the present application, which clearly and unambiguously discloses nucleic acid sequences and accession numbers corresponding to the various segments of the T cell receptor ß gene (i.e., splice variants), including the JB1 and JB2 segments (SEQ ID NOs: 1-14), and the CB1 and CB2 segments (SEQ ID NOs: 15 and 16), which are the targets of the target probes described in the present application. Additionally, FIGS. 1 and 2 clearly and unambiguously illustrate the differential splicing of the T cell receptor ß gene, which forms the basis of the detection strategy encompassed by the compositions, methods, and kits of the currently pending claims.
The above argument has been considered and has not been found persuasive for as noted above, applicant in the as-field Sequence Listing has asserted that each of the sequences is DNA, Artificial and Synthetic. Upon review of Table 1 it is noted that the table does not identify the species of mammal that the sequences are from, or found therein. It is further noted that neither the Sequence Listing nor Table 1 provides any RNA sequence. Applicant’s nondisclosure of such essential material5 has not been found to satisfy the written description requirements.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-11, 18-20, 23-24, 33, and 40 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) 1-11, 18, 19, 23, and 24 and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2001/0053519 A1 (Fodor et al.) in view of US 5,175,384 (Krimpenfort et al.), US 2013/0023433 (Luo et al.), US 11,821,026 B2 (Dunaway et al.), and US 2003/0129611 A1 (Bao et al.).
Fodor et al., in paragraph [0101], teach:
[0101] A powerful form of the generic array is the n-mer array. N-mer arrays comprise a solid support to which are attached all possible nucleic acid sequences of a give[n] length. Therefor, a 2-mer array comprises all possible oligonucleotides containing 2 base positions. Because each position can be filled with one of four possible bases, adenine (A), cytosine (C), thymine (with uracil replacing thymine in RNA) (T(U)), and guanine (G), an n-mer array comprising all possible n-mers contains 4.sup.n different oligonucleotide probes. Thus, a 2-mer array comprises 4.sup.2 or 16 different oligonucleotide sequences. A 10-mer array comprises 4.sup.10 or 1,048,576 distinct sequences and a 25-mer array comprises 4.sup.25 or over 1.times.10.sup.15 different oligonucleotide sequences. (Emphasis added)
As evidenced above, Fodor teaches the production and use of an n-mer array which comprises all oligonucleotides of a given length. Given such, the n-er array must comprise all possible sequences found in any and all mRNA molecules and all complements thereto as well as the nucleotide sequence for any T and L section. It is further noted that a compound and its properties ae inseparable. Given such, the oligonucleotides/probes of the array must encompass that which would bind to any and all T cell receptor sequences, including that of Jβ1, Jβ2, Cβ1, and Cβ2.
Krimpenfort et al., at column 17, last paragraph, teach performing hybridization reactions so to evaluate Jβ1 and Cβ1 target sequences. As stated therein:
For hybridization we used previously described C.alpha. and C.beta. probes were used (Dembic, et al. (1985) Nature 314, 271-273; Snodgrass, et. al. (1985) Nature 313, 592-595. The J.beta.2 probe is a 1.2 kb CIaI-EcoRI fragment located immediately downstream of the J.beta.2 gene segments (Cien, et al. (1984) Nature 309, 322-326). The D.beta.1 probe is a 1.4 kb upstream of the D.beta.2 gene segment (Siu, et al. (1984) supra. The C.beta.1-specific probe was derived from the 3' untranslated region as described by Gascoigne, et al. (1984) Nature 310, 387-391. The transgene-specific VDJ probe is an oligonucleotide of 30 residues in length identical to the complementary strand of the underlined cDNA sequence shown in FIG. 3A from position 581 to 610. V.beta.7, V.beta.9, V.beta.11, V.beta.12, V.beta.14, V.beta.15 and V.beta.16 probes have been described by Lai, et al. (1987) Proc. Natl. Acad. Sci. USA 81, 3846-3850. (Emphasis added)
Krimpenfort et al., at column 22, first paragraph, teach using probes to detect Cβ1 and Cβ2. As disclosed therein:
Rearrangement of endogenouse .beta. genes can be distinguished from the rearranged transgene by using specific hybridization probes. With a C.beta. probe, rearrangements of the C.beta.1 locus can be separated from those at the C.beta.2 locus (which is present in the transgene) if HindIII-digested T cell DNa is analyzed. T
Krimpenfort et al., at column 22, second paragraph, teach:
With a probe derived from the 5' flanking region of the D.beta.1 gene segment, a series of discrete rearranged fragements is again seen in transgenic but not in control T cell, nor in transgenic B cell, DNA (FIG. 10B). This result shows that partial D.beta.1 rearrangements, presumably to J.beta.1 and J.beta.2 gene segments, are present in unusually high frequencies in the transgenic mouse.
As evidenced above, the T cell receptor targets of Jβ1, Jβ2, Cβ1 and Cβ2 were known and have been the subject of nucleic acid analysis through the use of complementary probes.
While Krimpenfort et al., teach using probes in hybridization reactions, they have not been found to teach the probes comprising a T and L section, and that the probes can be pooled.
Luo et al., in paragraphs [0121] – [0127], sets forth a method of detecting nucleic acids via hybridization of probes to target where the capture probe comprises a T ad L section, where the T section is complementary to a region (applicant’s “portion”) of the target.
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Luo et al., in paragraph [0896], teach having probes in pools and that to do so overcomes some of the problems of multiplexing.
Dunaway et al., at column 47, last paragraph, teaches benefit of using probe pools. As disclosed therein:
To ensure that a user “captures” as many target nucleic acid molecules as possible from high fragmented samples, it is helpful to include a plurality of capture probes, each complementary to a different region of the target nucleic acid. For example, there can be three pools of capture probes, with a first pool complementary to regions of the target nucleic acid near its 5′ end, a second pool complementary to regions in the middle of the target nucleic acid, and a third pool near its 3′ end. This can be generalized to “n-regions-of-interest” per target nucleic acid. (Emphasis added)
The above showing is deemed to fairly teach additional limitations of each of independent claims 1, 23, and 33.
Fodor et al., has not been found to include the n-mer array in a kit with signal generating complex where one would be targeting mRNA molecules.
Bao et al., in paragraph [0060], teach:
[0060] Probes based on the nucleotide sequences can be used to detect or amplify transcripts or genomic sequences encoding the same or homologous proteins. In other embodiments, the probe further comprises a label group attached thereto, e.g., the label group can be a radioisotope, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a genomic marker test kit for identifying cells which express a particular protein, such as by measuring a level of the protein-encoding nucleic acid in a sample of cells, e.g., detecting the target nucleic acid mRNA levels or determining whether the gene encoding the mRNA has been mutated or deleted. (Emphasis added)
In view of the above presentation, it would have been obvious to one of ordinary skill in the art to have pooled combinations of probe in the array of Fodor et al., as such would have enhanced one’s ability to detect sequences associated with specific targets, thereby reducing the cost associated with producing probes that were not needed. It would have also been obvious to have designed the probe pools where they were directed to T cell receptor targets, including that of Jβ1, Jβ2, Cβ1, and Cβ2, as disclosed by Krimpenfort et al.
In view of the well-developed state of the art, and the medical significance in detecting such targets, said ordinary artisan would have been amply motivated and would have had a most reasonable expectation of success be it towards the claimed method, composition or kit. Given such, and in the absence of convincing evidence to the contrary, claims 1-11, 18, 19, 23, 24, and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2001/0053519 A1 (Fodor et al.) in view of US 5,175,384 (Krimpenfort et al.), US 2013/0023433 (Luo et al.), US 11,821,026 B2 (Dunaway et al.), and US 2003/0129611 A1 (Bao et al.).
Claim(s) 20 and 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2001/0053519 A1 (Fodor et al.) in view of US 5,175,384 (Krimpenfort et al.), US 2013/0023433 (Luo et al.), US 11,821,026 B2 (Dunaway et al.), and US 2003/0129611 A1 (Bao et al.) as applied to claims 1-11, 18, 19, 23, 24, and 33 above, and further in view of US 2004/0018529 A1 (Li et al.).
Neither Fodor et al., Krimpenfort et al., Luo et al., Dunaway et al., nor Bao et al., have been found to disclose the hybridization buffer limitation newly added to claims 20 and 40.
Lao et al., in paragraph [0751], does teach using fluorescently labeled probes for the detection of mRNA. Given such, the labeled nucleic acid probes are to be present in a hybridization buffer.
Li et al., at paragraph [0105], teach:
In a preferred embodiment, "stringent conditions" or "high stringency conditions," as defined herein, may be hybridization in 50% formamide, 5.times.SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5.times. Denhardt's solution, sonicated salmon sperm DNA (50 .mu.g/ml), 0.1% SDS, and 10% dextran sulfate at 42.degree. C., with washes at 42.degree. C. in 0.2.times.SSC (sodium chloride/sodium citrate) and 50% formamide at 55.degree. C., followed by a high-stringency wash consisting of 0.1.times.SSC containing EDTA at 55.degree. C. (Emphasis added)
As evidenced above, Li et al., teach inclusion of sonicated salmon sperm DNA, which is recognized as being single stranded.
In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art to have included in the composition and kit a hybridization buffer that comprised the components identified by Li et al. as such would have enabled the artisan to more effectively determine the status of T cell receptors Jβ1, Jβ2, Cβ1, and Cβ2, as disclosed by Krimpenfort et al.
In view of the above presentation and in the absence of convincing evidence to the contrary, claims 20 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over US 2001/0053519 A1 (Fodor et al.) in view of US 5,175,384 (Krimpenfort et al.), US 2013/0023433 (Luo et al.), US 11,821,026 B2 (Dunaway et al.), and US 2003/0129611 A1 (Bao et al.) as applied to claims 1-11, 18, 19, 23, 24, and 33 above, and further in view of US 2004/0018529 A1 (Li et al.).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
1 US 3,624,257 (Sakai). See column 9, fourth paragraph.
2 US 3,755,089 (Heimer). See column 3, first paragraph.
3 “Mammal”, Wikipedia, accessed 05/11/2023, pages 1-49.
4 US 5,612,035 (Howell et al.), column 2, first paragraph.
5 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.
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