DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I and the species of the luminal subtype of cancer and the combination of the UPK2 and UPK1A genes in the reply filed on 05 June 2026 is acknowledged.
Claim Status
3. Claims 33-52 are pending.
Claims 42, 44, and 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Note that claim 42 encompasses the non-elected species of methods that require determining the expression level of miRNAs; claim 44 encompass the non-elected species of methods that characterize each of the subtypes of luminal, luminal-papillary, luminal-infiltrated, basal-squamous and neuronal (i.e., the combination of all 5 subtypes); and claim 46 is limited to methods that identify the subtype therapy for only non-elected subtypes (i.e., this claim does not include a subtype therapy for the luminal subtype)
Claims 51 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 33-41, 43, 45 and 47-50 read on the elected invention and have been examined herein to the extent that the claims read on the elected subject matter of methods that detect the luminal subtype of cancer based on the expression of the combination of UPK2 and UPK1A. The claims encompass the non-elected subject matter of the additionally recited subtypes and combinations of the subtypes and the non-elected genes and combinations of genes other than the luminal subtype and the combination of the UPK2 and UPK1A genes. Prior to the allowance of claims, any non-elected subject matter which has not been rejoined with the elected subject matter will be required to be removed from the claims.
Note that claim 33 recites that the method is one “to characterize the sample to subtypes differentiated based at least in part on two or more of: luminal markers…luminal-papillary markers…”. Since Applicant elected the single subtype of the luminal subtype, the claims have been examined only to the extent that the method is one that characterizes the sample with respect to the luminal subtype.
Objection to Drawings / Objection to the Specification
4. The drawings are objected to under 37 CFR 1.83(a). The specification describes some of the figures in terms of particular colors. For example, figure 8 is described in terms of the color blue (see para [0065]; paragraph numbering herein is with respect to the published application). Figure 22 includes the description of the drawing in terms of yellow, blue and green. However, the figures have been filed in black and white. Thus, the description of the figures in the specification is not consistent with the drawing and the specification is thereby also objected to.
If the drawings are intended to be in black and white, the specification should be amended to delete the reference to the recited colors. Alternatively, corrected drawing sheets in compliance with 37 CFR 1.121(d) are required. Note that color drawings are only accepted on rare occasions when they are the only practical medium by which to disclose the subject matter to be patented. See MPEP 608.02(VIII).
Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
If color photographs or color drawings are submitted, it is noted that color photographs and color drawings are not accepted unless a petition filed under 37 CFR 1.84(a)(2) is granted.
A petition for color drawings must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via EFS-Web or three sets of color drawings or color photographs, as appropriate, if not submitted via EFS-Web, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Appropriate correction is required.
5. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code – see, for example, para [0065], [0288], [0310] and [0330]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code, such as “www.”. See MPEP § 608.01.
6. The use of the term Random Forests™, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
This is one example of a trademark that is used in the specification. The specification should be reviewed for any additional trademarks or trade names and the terms should be accompanied by their generic terminology and capitalized or where appropriate accompanied by a proper symbol.
Improper Markush Grouping Rejection
7. Claims 33-41, 43, 45 and 47-50 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of the UPK2, UPK1A, FOXA1, GATA3, PPARG, KRT20, SNX31, FGFR, FGFR3-TACC3 fusions, IncRNAs DANCR, GAS5, MALAT1, NEAT1, NORAD (LINC00657), UCAI,ZNF667-AS1 (MORT), LINC00152, GATA3, FOXA1, PPARy, TP63, sonic-hedgehog signaling (SHH), CD274 (PD-L1) and PDCD1 (PD-1), CD44, KRT5, KRT6A, KRT14, COL17A1, TGM1, DSC3, TP63, GSDMC, PI3, TP53, CRTAC1, CTSE, PADB, MSN, and NR3C1, CD274, PDCD1LG2, 1D01, CXCL11, LICAM, SAAJ1, CTLA4; MSI1, PLEKHG4B, GNG4, PEG10, RND2, APLP1, SOX2, TUBB2B, TP53, RB1 and E2F3 and neuroendocrine markers CHGA, CHGB, SCG2, ENO2, SYP, NCAM1, and genes / targets listed in Tables 2-4, and combinations thereof are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
It is first noted that MPEP 2117 states that “A Markush claim may be rejected under judicially approved "improper Markush grouping" principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an "improper Markush grouping" if either: (1) the members of the Markush group do not share a "single structural similarity" or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)). “ Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class (prong 1) and the members of a Markush group share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent (prong 2).
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.” (see MPEP 2117IIA).
Herein, the recited alternative species do not share a single structural similarity, as each gene has a different chemical structure in that it consists of a different nucleotide sequence. The only structural similarity present is that all of the genes comprise nucleotides. The fact that the genes comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides alone is not essential to the asserted common activity of being correlated with a cancer subtype or responsiveness of a cancer to treatment. Accordingly, while the different genes are asserted to have the property of being correlated with a cancer subtype or responsiveness of a cancer to treatment, they do not share a substantial structural similarity essential to this activity.
Further, the recited genes do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that genes behave in the same manner and can be substituted for one another with the same intended result achieved. There is no evidence of record to establish that it is clear from their very nature that the recited genes possess the common property of being diagnostic of a cancer subtype / responsiveness of the cancer to treatment.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
In particular, this rejection may be obviated by amendment of the claims to recite characterizing the sample as having the luminal subtype based on the expression levels of UPK2 and UPK1A.
Claim Rejections - 35 USC § 101
87. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 33-41, 43, 45 and 47-50 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature / natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant' s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” which discusses the Alice/Mayo two-part test for evaluating subject matter eligibility.
Regarding Step 1 of the subject matter eligibility test set forth at MPEP 2106III, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite the correlation between the level of expression of UPK2 and UPK1A and the luminal subtype of cancer, as well as a correlation between the luminal subtype of a particular therapy - i.e., a “subtype-directed therapy.” As in Mayo Collaborative Services v. Prometheus, the recited relationship is a natural phenomenon that exists apart from any human action. See also Cleveland Clinic Foundation v. True Health Diagnostic, LLC, 2018-1218 (Fed Cir. 2019) which states that “The re-phrasing of the claims does not make them less directed to a natural law.”
The claims also recite the judicial exception of an abstract idea and particularly mental processes.
MPEP 2106.04(a) states that the enumerated groupings of abstract ideas include:
“1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);…
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).”
The claims require performing the step of “identifying” a subtype-directed therapy based on a received subtype characterization. The broadest reasonable interpretation of the “identifying” step is that this step may be accomplished by reading information in a database or report regarding a subtype characterization and then mentally identifying a therapy that treats the subtype. Such “identifying” thereby encompasses processes that may be performed mentally and thus is an abstract idea.
The claims recite “reporting" the subtype characterization and subtype-directed therapy. As broadly recited, the reporting be accomplished verbally. Such verbal communication is also abstract, having no particular concrete or tangible form.
The claims also recite “providing the expression levels to a genomic classifier, the genomic classifier to measure the expression levels against reference expression pattern profiles to characterize the sample to subtypes differentiated based.” Note that comparing per se may be accomplished by critical thinking processes. The use of a classifier to compare expression levels to reference levels and provide the result of a classification of the subtype of cancer is also considered to be an abstract idea since using a generic computer or software program to implement an abstract idea does not itself impart patent eligibility.
As stated in MPEP 2106.04(a)(2) III “The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation” and that “Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer.”
Herein, the use of a generic computer to apply a generic algorithm to compare expression levels and classify the subtype of lung squamous cell carcinoma samples does not constitute something more than an abstract idea.
Also, the use of the machine learning algorithms and/or models recited in the dependent claims to compare expression levels constitutes a judicial exception of a mathematic concept.
See MPEP 2106.04I which states “mathematical formulas are considered to be a judicial exception as they express a scientific truth, but have been labelled by the courts as both abstract ideas and laws of nature.”
See also MPEP 2106.04(a)(2):
“A claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the “mathematical concepts” grouping. A mathematical calculation is a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. There is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word “calculating” in order to be considered a mathematical calculation. For example, a step of “determining” a variable or number using mathematical methods or “performing” a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation.
Examples of mathematical calculations recited in a claim include:…
v. using an algorithm for determining the optimal number of visits by a business representative to a client, In re Maucorps, 609 F.2d 481, 482, 203 USPQ 812, 813 (CCPA 1979); and
vi. calculating the difference between local and average data values, In re Abele, 684 F.2d 902, 903, 214 USPQ 682, 683-84 (CCPA 1982).”
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s).
As discussed above, identifying a subtype-directed therapy is an abstract step and does not involve administering a particular therapy.
See MPEP 2106.04(d)(2):
Examiners should keep in mind that in order to qualify as a "treatment" or "prophylaxis" limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of such a limitation is a step of "administering amazonic acid to a patient" or a step of "administering a course of plasmapheresis to a patient." If the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. For example, a step of "prescribing a topical steroid to a patient with eczema" is not a positive limitation because it does not require that the steroid actually be used by or on the patient, and a recitation that a claimed product is a "pharmaceutical composition" or that a "feed dispenser is operable to dispense a mineral supplement" are not affirmative limitations because they are merely indicating how the claimed invention might be used.
Even if the claims recited a step of administering a luminal-directed therapy to a subject classified as having the luminal subtype, as generically recited this constitutes merely an “apply it” limitation. None of the claims specifically states the identity of a particular “subtype-directed therapy” for the luminal subtype of cancer.
Regarding specific treatments, see MPEP 2106.04(d)(2):
When determining whether a claim applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, the following factors are relevant.
a. The Particularity Or Generality Of The Treatment Or Prophylaxis
The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application….
b. Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)
The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). For example, consider a claim that recites a natural correlation (law of nature) between blood glucose levels over 250 mg/dl and the risk of developing ketoacidosis (a life-threatening medical condition). The claim also recites "treating a patient having a blood glucose level over 250 mg/dl with insulin". Insulin acts to lower blood glucose levels, and administering insulin to a patient will reduce the patient’s blood glucose level, thereby lowering the risk that the patient will develop ketoacidosis. Thus, in the context of this claim, the administration step is significantly related to the recited correlation between high blood glucose levels and the risk of ketoacidosis. Because insulin is also a "particular" treatment, this administration step integrates the law of nature into a practical application. Alternatively, consider a claim that recites the same law of nature and also recites "treating a patient having a blood glucose level over 250 mg/dl with aspirin." Aspirin is not known in the art as a treatment for ketoacidosis or diabetes, although some patients with diabetes may be on aspirin therapy for other medical reasons (e.g., to control pain or inflammation, or to prevent blood clots). In the context of this claim and the recited correlation between high blood glucose levels and the risk of ketoacidosis, administration of aspirin has at best a nominal connection to the law of nature, because aspirin does not treat or prevent ketoacidosis. This step therefore does not apply or use the exception in any meaningful way. Thus, this step of administering aspirin does not integrate the law of nature into a practical application.
Regarding the reporting step, as discussed above, this step is an abstract idea. Further, see MPEP 2106.05(a)
Examples that the courts have indicated may not be sufficient to show an improvement to technology include:
i. A commonplace business method being applied on a general purpose computer, Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1976; Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015);
ii. Using well-known standard laboratory techniques to detect enzyme levels in a bodily sample such as blood or plasma, Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1355, 1362, 123 USPQ2d 1081, 1082-83, 1088 (Fed. Cir. 2017);
iii. Gathering and analyzing information using conventional techniques and displaying the result, TLI Communications, 823 F.3d at 612-13, 118 USPQ2d at 1747-48
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The claims do not require performing any specific, non-conventional transformative active process steps.
Regarding the use of classifiers, training algorithms and models, using machine learning algorithms and models to compare expression levels was well-known, routine and conventional in the prior art, as evidenced by the teachings in the specification (e.g., para [0188]).
Further, MPEP 2106.05(a) states that ”Limitations that the courts have found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include: i. Adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, e.g., a limitation indicating that a particular function such as creating and maintaining electronic records is performed by a computer, as discussed in Alice Corp., 134 S. Ct. at 2360, 110 USPQ2d at 1984 (see MPEP § 2106.05(f))”
In Mayo v. Prometheus, the Supreme Court stated: "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377, 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
9. 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.
Claims 33-41, 43, 45 and 47-50 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.
Claims 33-41, 43, 45 and 47-50 are indefinite over the recitation of the “markers listed in Tables 2-4.”. As stated in MPEP 2173.05(s), claims should be complete to themselves and the reference to Tables 2-4 renders the claims incomplete. Claims which recite figures or tables are only permitted in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into a claim.
Claims 33-41, 43, 45 and 47-50 are indefinite over the recitation of “providing the expression levels to a genomic classifier, the genomic classifier to measure the expression levels against reference expression pattern profiles to characterize the sample to subtypes differentiated based at least in part on two or more of” the recited markers because it is unclear as to what is meant by this phrase. It is unclear as to what is meant by the classifier measuring the expression levels “against” expression pattern profiles and it is unclear as to what is meant by this step resulting in “to characterize the sample to subtypes.”
Claims 34-41, 43, 45 and 47-50 are dependent on canceled claims - e.g., canceled claims 1, 3, 6, 9 and 14 - and are therefore “incomplete.” See MPEP 608.01(n)(V). Additionally, it is unclear as to what is intended to be encompassed by the dependent claims since they do not depend from a specific pending claim.
Claim 36 contains the trademark/trade name Random Forests™. MPEP 2173.05 states “If the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982).”The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a particular type of algorithm and, accordingly, the identification/description is indefinite.
Claim 39 is indefinite and unclear as to whether “Robust-Multi-Array (RMA) algorithm” is intended to be distinct from “an algorithm selected from….RMA” and if so it is unclear as to the distinction between an RMA algorithm and an algorithm that is RMA.
Claim 40 is indefinite over the recitation of “wherein the expression levels are detected using whole exome sequencing…” because it is unclear as to how this recitation is intended to further limit the claim. The claim does not previously recite a step of detecting expression levels. Rather, the claim (to any extent that it is intended to depend from claim 33 rather than cancelled claim 1) recites a step of receiving expression levels. Thereby, it is unclear as to whether claim 40 is intended to include a step of detecting expression levels in addition to receiving the expression levels or if claim 40 intends to define how the received expression levels were previously detected.
Claim 43 is indefinite and vague over the recitation of “the detection or the lack of detection of an umbrella cell phenotype in the sample” because the claim does not set forth the criteria for how one or how the classifier ascertains if an umbrella cell phenotype is present in the sample.
Claim Rejections - 35 USC § 112(a) - Enablement
10. 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.
Claims 33-41, 43, 45 and 47-50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods that detect an increase in the level of expression of UPK2 and UPK1A in a urothelial tumor tissue sample, as compared to a reference control level of expression of UPK2 and UPK1A, as indicative of a luminal subtype of urothelial cancer that will be responsive to treatment with atezolizumab,
does not reasonably provide enablement for methods that characterize any type of cancer as being a luminal subtype based on the detection of an increase or decrease in the level of expression of UPK2 and UPK1A in any type of sample as compared to any reference expression pattern profile or methods which identify any luminal “subtype-directed therapy.” The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The following factors have been considered in formulating this rejection (In re Wands, 858F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988): the breadth of the claims, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, the amount of direction or guidance presented, the presence or absence of working examples of the invention and the quantity of experimentation necessary.
The claims encompass methods that characterize any type of cancer as being a luminal subtype of cancer based on detecting an increase or decrease in the expression level of UPK2 and UPK1A as compared to any reference expression profile.
However, the teachings in the specification are limited to urothelial cancer. See, for example, para [0211]. Regarding the urothelial tumor tissue samples analyzed, it is disclosed that “The luminal subtype had the highest expression levels of several uroplakins (UPK1A, UPK2) and genes that are highly expressed in terminally differentiated urothelial umbrella cells (KRT20, SNX31) (FIG. 5 ). This suggested that these tumors were derived from intermediate cells that have a transcriptional program that leads to expression of markers characteristic of normal umbrella cells” (para [0227]).
The specification does not teach that UPK2 and UPK1A are expressed at increased or decreased levels of other types of luminal cancers, such as luminal breast cancers. In the absence of any information regarding UPK2 and UPK1A expression levels in a representative number of different types of luminal cancers, it is highly unpredictable as to whether an increase or decrease in the level of UPK2 and UPK1A can be used to identify other types of cancers as being of the luminal subtype and distinguishing the luminal subtype from other subtypes. Such characterization of other types of cancers can only be obtained through experimentation, the results of which are unpredictable.
Secondly, the specification does not teach any “luminal subtype-directed therapies” - i.e., therapies that specifically target the luminal subtype of urothelial cancer or other types of cancer.
Rather, the specification (para [0267] states:
“The luminal subtype had the highest expression levels of several uroplakins (UPK1A, UPK2) and genes that are highly expressed in terminally differentiated urothelial umbrella cells (KRT20, SNX31) (FIG. 5 ). This suggested that these tumors were derived from intermediate cells that have a transcriptional program that leads to expression of markers characteristic of normal umbrella cells.”
In Figure 14, the drawing has a question marking regarding targeted therapy for luminal urothelial cancers, as shown below:
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516
1008
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Greyscale
The specification (para [0274]) does teach that luminal bladder cancers had a better response to treatment with atezolizumab than 3 other subtypes of bladder cancers, but the response was not as pronounced as in neuronal cancers:
“Remarkably, the neuronal subtype defined by the TCGA 2017 classifier (SOX2, TUBB2B, PEG10) showed a high objective response rate and had the best overall survival (p=0.012, FIG. 31 A,B, C). The luminal subtype was also associated with both a better response rate (38%) and overall survival than the other three subtypes, but to a much smaller degree (FIG. 31C).”
Accordingly, the disclosure makes clear that there is currently no known luminal “subtype-directed therapy,” but that atezolizumab can be used to treat the luminal subtype of urothelial cancers.
The specification does not provide sufficient guidance as to how to predictably identify additional therapies that are correlated with higher levels of expression of UPK2 and UPK1A and which are luminal subtype-directed therapies. Such information can only be ascertained by trial-by-error experimentation. Gene expression may be influenced by a number of factors, in addition to disease itself, and these factors must be considered prior to drawing any conclusions regarding an association between gene expression patterns and prognostic factors or responsiveness of a subject to a particular treatment. While methods for expression profiling are known in the art, such methods provide only the general guidelines that allow researchers to search for mRNAs or proteins whose expression patterns may linked to the occurrence of a particular phenotype. The results of performing such methodology are highly unpredictable. The specification has provided only an invitation to experiment. Accordingly, undue experimentation would be required to determine other types of luminal cancers and other types of therapies that are correlated with an increase or decrease in the expression level of UPK2 or UPK1A, or with luminal cancers per se, as compared to any reference level.
The unpredictability in the art is supported by the teachings in the specification in para [0272] which indicate that while etoposide-cisplatin therapy is recommended in neoadjuvant and metastatic settings, as for neuroendocrine neoplasms arising in other sites “this should also be tested in prospective clinical trials.”
35 USC 112 first paragraph requires that the invention is enabled at the time the invention is made. "[T]o be enabling, the specification.., must teach those skilled in the art how to make and use the full scope of the claimed invention without 'undue experimentation.'" Wright, 999 F.2d at 1561, 27 USPQ2d at 1513 (emphasis added), quoted in Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2 1001, 1004 (Fed. Cir. 1997). Thus, "there must be sufficient disclosure, either through illustrative examples or terminology, to teach those of ordinary skill how to make and how to use the invention as broadly as it is claimed." In re Vaeck, 947 F.2d 488, 496 & n. 23, 20 USPQ2d 1438, 1445 & n. 23 (Fed. Cir. 1991), quoted in Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1372, 52 USPQ2d 1129, 1138 (Fed. Cir.1999).
Further, as set forth in Rasmusson v. SmithKline Beecham Co., 75 USPQ2d 1297, 1302 (CAFC 2005), enablement cannot be established unless one skilled in the art "would accept without question" an Applicant's statements regarding an invention, particularly in the absence of evidence regarding the effect of a claimed invention. Specifically:
"As we have explained, we have required a greater measure of proof, and for good reason. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the "inventor" would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis."
In the present situation, in view of the high level of unpredictability in the art, and the lack of disclosure and guidance provided in the specification and in the prior art, it would require undue experimentation for one of skill in the art to make and use the invention as broadly claimed.
Priority
11. The present claims are not entitled to priority to provisional application 62/628,756, filed 02/09/2018. It is noted that a claim as a whole is assigned an effective filing date rather than the subject matter within a claim being assigned individual effective filing dates. The ‘756 application does not provide support for each of the embodiments in independent claim 33 and each of the embodiments in the dependent claim. For example, the ‘756 application does not teach the limitation of identifying a luminal subtype-directed therapy and reporting the luminal subtype-directed therapy and does not provide enablement for methods that identify and report a luminal subtype-directed therapy. In Figure 14 of the ‘756 application a question mark is provided for a “Targeted therapy” for luminal subtypes.
If Applicant asserts that the present claims are entitled to priority to the provisional applications, Applicant should point to specific teachings (e.g., by page and line number) in the priority applications to establish priority for each of the recitations set forth in the claims.
See MPEP 2163 II at “(b) New Claims, Amended Claims, or Claims Asserting Entitlement to the Benefit of an Earlier Priority Date or Filing Date under 35 U.S.C. 119, 120, 365, or 386” states “To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure.”
See also MPEP 211.05: “(t)he written description and drawing(s) (if any) of the provisional application must adequately support and enable the subject matter claimed in the nonprovisional application that claims the benefit of the provisional application.”
Claim Rejections - 35 USC § 103
12. 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.
Claim(s) 33-36, 38, 39, 41, 45, and 47-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConkey et al (U.S. 20150292030; cited in the IDS) in view of Griffith et al (U.S. 20140018253).
McConkey teaches a method for identifying a subtype of bladder cancer comprising: assaying a sample from a subject to determine the expression level of UPK2 and UPK1A; comparing the expression levels to reference expression levels, including expression levels stored on a computer, using a class comparison software program; and identifying the subtype of bladder cancer as being a luminal subtype based on detecting an increase in the level of expression of UPK2 and UPK1A in the sample as compared to the reference level (e.g., para [0007], [0010-0011], [0060-0061], [0111] and [0119]). McConkey teaches using the results of the expression analysis to identify and report a treatment for the bladder cancer patient (e.g., para [0017] and [0073]). It is also disclosed that bladder cancer patients identified as having a luminal subtype of bladder cancer (“cluster 3”) can be treated by administering a FGFR inhibitor and particularly a FGFR3 inhibitor therapy (e.g., para [0010-0011], [0053]), and that the anti-FGFR agent may be a tyrosine kinase inhibitor (para [0097]).
McConkey does not teach that the method is a computer-implemented method that comprises receiving the expression levels of UPK2 and UPK1A; receiving the information regarding the bladder cancer being a luminal subtype of bladder cancer; identifying a therapy for the subtype based on the received information; and reporting the subtype of the bladder cancer as being a luminal subtype and a therapy for the luminal subtype of bladder cancer.
However, Griffith teaches computer-implemented methods for diagnosing cancer based on gene expression levels, wherein the method comprises receiving, in a computer system, information regarding gene expression levels in a sample from a subject; using a computer processor and a random forest algorithm to compare the gene expression levels with reference gene expression levels and identifying a cancer phenotype based on the comparison (e.g., para [0010-0011], [0072]). Griffith teaches generating a report regarding the gene expression levels and the diagnosis of the patient (para [0074]) and the use of this information to provide a therapeutic strategy for the patient (e.g., abstract; para [0005], [0031] and [0063]).Griffith teaches that computer-implemented methods provide a means for easily accessing, storing and distributing information (e.g., [0078-0084]) and “provide rapid and useful information for clinical decision making” (para [0006]).
In view of the teachings of Griffith, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a computer to implement the method of McConkey. In particular, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of McConkey so as to have used a computer system to receive information regarding the expression levels of UPK2 and UPK1A in a sample from a patient; used a classifier such as a random forest classifier to compare the expression levels of UPK2 and UPK1A in the sample from the patient with reference levels; to have used the results of the comparison to identify the cancer as a luminal subtype when the level of expression of UPK2 and UPK1A in the patient’s samples was increased relative to a reference level; and to have provided a report indicating that the patient had a luminal subtype of bladder cancer and indicating that the patient should be treated with a therapy directed to treating a luminal subtype of bladder cancer, such as treatment with a FGFR3 inhibitor. One would have been motivated to have done so for the advantages associated with computer-implemented methods of providing a method that rapidly processes expression information, stores the expression information and results of the comparison of the expression information with reference levels, including information regarding the subtype of bladder cancer and the most suitable therapy for a patient having the luminal subtype of bladder cancer, and for the benefits associated with readily reporting the clinical information regarding the patient’s subtype and selection of therapy to the patient and medical personnel.
Regarding claims 34-36, as discussed above, modification of the method of McConkey so as to have used a computer processor, as taught by Griffith, to receive the gene expression information and to compare the gene expression information with reference profile levels would have resulted in a method that uses a random forest classifier to accomplish the classifying step.
Regarding claims 38 and 39, McConkey teaches normalizing expression levels using BRB ArrayTools (para [0111]), which is a class prediction model that uses a robust multi-array algorithm (RMA).
Regarding claim 41, McConkey teaches that the method is one in which the gene expression levels are expression levels of mRNA (e.g., para [0053] and [0074]).
Regarding claims 45, 47 and 48, these claims encompass methods wherein the “subtype-directed therapies” is limited to administration of a tyrosine kinase inhibitor of FGFR3. McConkey teaches that patient’s identified as having the luminal (cluster 3) subtype of bladder cancer should be administered a tyrosine kinase inhibitor of FGFR3, and particularly PD173074 (e.g., para [0011], [0020] and [0053]; and claim 37).
Additionally, regarding claim 48, it is noted that the information / written material in the report is not considered to be within the statutory classes and does not materially distinguish the claimed method over that of McConkey. See MPEP 2111.05 which states:
“The first step of the printed matter analysis is the determination that the limitation in question is in fact directed toward printed matter. “Our past cases establish a necessary condition for falling into the category of printed matter: a limitation is printed matter only if it claims the content of information.” See In re DiStefano, 808 F.3d 845, 848, 117 USPQ2d 1265, 1267 (Fed. Cir. 2015). “[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight.” Id. at 850, 117 USPQ2d at 1268. If a new and nonobvious functional relationship between the printed matter and the substrate does exist, the examiner should give patentable weight to printed matter. See In re Lowry, 32 F.3d 1579, 1583-84, 32 USPQ2d 1031, 1035 (Fed. Cir. 1994); In re Ngai, 367 F.3d 1336, 70 USPQ2d 1862 (Fed. Cir. 2004); In re Gulack, 703 F.2d 1381, 1385, 217 USPQ 401, 403-04 (Fed. Cir. 1983). The rationale behind the printed matter cases, in which, for example, written instructions are added to a known product, has been extended to method claims in which an instructional limitation is added to a method known in the art. Similar to the inquiry for products with printed matter thereon, in such method cases the relevant inquiry is whether a new and nonobvious functional relationship with the known method exists.”
MPEP 2111.05 further states:
“where the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.”
In the present situation, the information in the report does not have a new and nonobvious functional relationship with the method steps of the claim and thereby does not materially distinguish the claimed method over that suggested by the combined teachings of McConkey and Griffith.
Regarding claims 49, McConkey does not specifically teach that the sample is a blood sample. However, McConkey discloses kits comprising reagents for isolating mRNA from blood samples so that the mRNA can be used for expression analysis (e.g., para [0102]). McConkey (para [0102] states: “these kits allow a practitioner to obtain samples of neoplastic cells in blood, tears, semen, saliva, urine, tissue, serum, stool, sputum, cerebrospinal fluid and supernatant from cell lysate.” Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of McConkey so as to have specifically used a blood as the source of the sample to assay for expression levels of UPK1A and UPK2. One would have been motivated to have done so because the teachings of McConkey indicate that blood is a source of neoplastic cells that can be used to assay for gene expression levels and the ordinary artisan would have recognized that a blood sample could be obtained from the patient in a non-invasive manner.
Regarding claim 50, McConkey teaches that the sample in which gene expression is detected may be a tumor tissue sample (e.g., para [0107] and [0117]).
13. Claims 37 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over McConkey et al (U.S. 20150292030; cited in the IDS) in view of Griffith et al (U.S. 20140018253) and further in view of Buerki et al (U.S. 20140066323).
The teachings of McConkey and Griffith are presented above.
Regarding claim 37, the combined teachings of McConkey and Griffith do not teach using an unsupervised machine learning algorithm as the genomic classifier.
However, Buerki teaches methods for diagnosing cancer in a subject wherein gene expression levels from a sample from a patient are compared with that of a reference expression profile using a classifier algorithm (e.g., para [0006]). Buerki teaches that while the classifier can be a supervised classifier, such as a Random Forest machine learning algorithm (para [0273]), the classifier may also be an unsupervised learning algorithm (para [0274]). Buerki (para [0274]) states:
“The machine learning algorithms may also comprise an unsupervised learning algorithm. Examples of unsupervised learning algorithms may include artificial neural network, Data clustering, Expectation-maximization algorithm, Self-organizing map, Radial basis function network, Vector Quantization, Generative topographic map, Information bottleneck method, and IBSEAD.”
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the method of McConkey so as to have used an unsupervised machine learning algorithm, including an artificial neural network or data clustering, to compare the expression levels with a reference gene expression profile and to classify the subject’s bladder cancer as luminal based on the comparison. One would have been motivated to have done so because Buerki teaches that unsupervised machine learning algorithm, including an artificial neural network or data clustering, can be effectively used in place of supervised machine learning algorithms, such as a rain forest algorithm, to compare expression data and provide classifications based on the comparison.
Regarding claim 40, McConkey teaches using microarrays to measure gene expression levels but does not teach performing whole genome sequencing to measure gene expression levels.
However, Buerki teaches that gene expression levels can be measured using whole genome sequencing or microarray analysis (e.g., para [0262-0263]).
In view of the teachings of Buerki, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of McConkey so as to have received gene expression levels that were measured by whole genome sequencing because Buerki teaches that this is an equally effective means for quantifying gene expression levels.14. Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over McConkey et al (U.S. 20150292030; cited in the IDS) in view of Griffith et al (U.S. 20140018253) and further in view of McConkey et al (Urol. Oncol. 2010. 28(4): 429-440; herein after “McConkey (2010)”).
The teachings of McConkey and Griffith are presented above.
The combined references do not teach the limitation that “the genomic classifier differentiates subtypes based at least in part on the detection or the lack of detection of an umbrella cell phenotype in the sample.”
However, McConkey (2010) teaches that gene expression profiling has been used to classify urothelial cancer as papillary/superficial and non-papillary/muscle-invasive (see abstract). It is disclosed that urothelial cancers contain subpopulations of cancer stem cells (abstract). McConkey (2010) teaches that the urothelium is comprised of 3 layers and the first layer is an “umbrella cell” (p. 8, 2nd full para). The reference (p. 21, Figure 4) states:
“The surface epithelium consists of a single layer of terminally differentiated urothelial cells (“umbrella cells”) that express uroplakins and cytokeratin-20 (CK20) and have a low proliferative potential. It is conceivable that papillomas arise from transformation of umbrella cells, but this would require that they “de-differentiate” to reacquire self-renewal potential. Below the umbrella cells is a multicellular layer of intermediate cells that express CK18 and variable levels of p63, CK5, and CD44. These are most likely “transit-amplifying cells” that possess higher proliferative potential but have also begun to differentiate towards the umbrella cell phenotype. Finally, adjacent to the basement membrane is a layer of basal cells that express high levels of CK5, CD44, p63 and the 67 kD laminin receptor. This layer contains urothelial stem cells, which are tightly regulated by stromal elements (cells and matrix proteins) contained within the “niche”. Recent studies indicate that urothelial cancer stem cells share several molecular markers with the normal basal cell, including CD44, CK5, and the 67 kD laminin receptor and that these markers are upregulated at the tumor-stromal interface in xenografts.”
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of McConkey (U.S. 20150292030) so as to have included in the genomic classifier information regarding the presence or absence of an umbrella cell phenotype. One would have been motivated to have done so because McConkey (2010) teaches the possible transformation of umbrella cells and the differentiation of cells in the urothelium during cancer progression. Thereby, including information in the genomic classifier regarding the presence or absence of an umbrella cell phenotype would have provided further information for classifying and monitoring changes in the urothelial cancer.
15. Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over McConkey et al (U.S. 20150292030; cited in the IDS) in view of Griffith et al (U.S. 20140018253) and further in view of Kiselynov et al (Int. J. Cancer. 2016. 136: 2562-2569).
The following rejection applies to claim 48 to the extent that the claim may intend to require that the therapy is an immune checkpoint therapy and that the immune checkpoint therapy is atezolizumab.
The teachings of McConkey and Griffith are presented above.
The combined references do not teach reporting that the “subtype-directed” therapy to be used to treat the subject is atezolizumab.
However, Kiselynov teaches that the anti-PDL1 antibody atezolizumab has been found to be effective in treating metastatic MIBC.(p. 2565, col. 1 final sentence to col. 2 first para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of McConkey so as to have reported that those patients identified as having luminal urothelial cancer could be treated with atezolizumab in those instances in which the urothelial cancer is metastatic MBC. Note that neither the specification nor the claims provide a limiting definition for what constitutes “subtype-directed therapy” and as broadly recited this phrase encompasses any therapy that could be used to treat the subtype.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached on M-Th 6:30-5:00 EST.
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 (Winston) Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CARLA J MYERS/Primary Examiner, Art Unit 1634
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