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 .
Status of the Application
This Office Action is in response to applicant’s arguments filed on 11/21/25. Claims 3, 5-6, 13-26, 29-30 have been cancelled. Claims 1-2, 4, 7-12, 27-28, 31-38 are pending. Claims 4, 7-12, 27-28, 31-34 have been withdrawn. Claims 1-2, 35-38 are examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and repeated below for Applicant’s convenience.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 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.
Claims 1-2, 35-38 are rejected under 35 U.S.C. 103 as being unpatentable over Navaneethan et al. ("Volatile organic compounds in bile can diagnose malignant biliary strictures in the setting of pancreatic cancer: a preliminary observation," Gastrointestinal Endoscopy 2014, 80(6), 1038-1045, of record) in view of Boyden et al. (WO 2017/137741, of record), Song et al. (“Quantitative breath analysis of volatile organic compounds of lung cancer patients,” 2010, Lung Cancer, 67, 227-231, of record), and Li et al. (“Pancreatic cancer,” The Lancet, 2004, vol. 363, pages 1049-1057, of record).
The instant claims are directed to a method of determining the efficacy of or treating pancreatic cancer in a subject by analyzing two signature compounds (acetoin - also known as 3-hydroxy-2-butanone) in a bodily sample and comparing this concentration with a reference, wherein an increase in concentration indicates that the subject is suffering from pancreatic cancer or that the treatment is ineffective, and administering a therapeutic agent capable of treating pancreatic cancer.
Navaneethan et al. teach that the identification of volatile organic compounds (VOCs) from a bile sample as potential biomarkers in the diagnosis of pancreatic cancer (page 1039, left column, paragraphs 2-4). Mass spec analysis comprised 22 common analytes, including 2-propanol, acetaldehyde, ethanol, pentane, and ethane (page 1039, right column, first paragraph). The concentration of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and TMA) were increased in the bile headspace of patients with pancreatic cancer compared to controls (page 1040, left column, last paragraph). Table 2 clearly shows a higher concentration of acetaldehyde found in patients with pancreatic cancer as compared to a control. Therefore, the study showed that patients with pancreatic cancer have a specific pattern of VOC print that is characterized by high levels of TMA, acetone, acetaldehyde, benzene, carbon disulfide, and pentane in the headspace compared with patients with benign biliary strictures (page 1041, bridging sentence). A significant increase in pentane in the biliary fluid headspace in pancreatic cancer suggests the contribution of lipid peroxidation. Navaneethan et al. also observed an increase in acetaldehyde in the VOC of bile in patients with pancreatic cancer. This is clinically significant because breath testing is an attractive option in diagnosing patients with cancer since VOCs are present in breath samples and would represent a noninvasive diagnosis of pancreatic cancer (pages 1042-1043).
However, Navaneethan et al. fail to disclose 3-hydroxy-2-butanone and therapeutic agents useful for treating pancreatic cancer.
Boyden et al. teach methods of diagnosing cancer in a subject by determining a level of one or more volatile organic compounds in cancer (title and abstract), wherein the cancer is pancreatic cancer (page 6, paragraphs 4-5; page 36, first full paragraph). In one embodiment, the biomarker is a C2-30 ketone, preferably a C3-14 ketone, for example acetone, 2-butanone, 2-pentanone, etc. (page 32, last paragraph).
Song et al. teach that 3-hydroxy-2-butanone taken from the breath is a well-known volatile organic compound used for the early diagnosis of cancer (abstract).
Li et al. teaches several therapeutic agents useful for treating pancreatic cancer. In the USA, adjuvant treatment with fluorouracil-based chemoradiation is frequently recommended (page 1053, left column, last paragraph). Gemcitabine is currently the standard care for metastatic pancreatic cancer (page 1054, left column, first paragraph). Table 2 on page 1054 lists several novel agents, such as the monoclonal antibody (C225, trastuzumab, bevacizumab), the receptor tyrosine inhibitors (ZD1839, OSI-774, SU5416, SU6668), and the farnesyl transferase inhibitors and antisense oligonucleotides (celecoxib and rofecoxib).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have combined 3-hydroxy-2-butanone, as taught by Boyden and Song et al., with acetaldehyde and pentane as the VOCs in the method of treating and diagnosing pancreatic cancer, as taught by Navaneethan and Li et al.
A person of ordinary skill in the art would have been motivated to combine 3-hydroxy-2-butanone with acetaldehyde and pentane because all three are known VOC biomarkers to be useful in the diagnosis of cancer, in general, and pancreatic cancer, specifically. Navaneethan et al. already teaches that ketones, in general, and acetone, specifically, can be used to detect pancreatic cancer. This is corroborated by Boyden et al. broader teaching that the biomarker for diagnosing pancreatic cancer can be a C2-30 ketone, preferably a C3-14 ketone, for example acetone or 2-butanone. Since Song et al. teach that 3-hydroxy-2-butanone is a well-known volatile organic compound and species to the broad teaching of ketones and 2-butanones, one of ordinary skill in the art would have had a reasonable expectation of success in using 3-hydroxy-2-butanone for the ketone, taught by Navaneethan and Boyden et al.
Examiner notes that this is a typical genus/species situation. Once a prima facie case of obviousness is established, the burden is shifted to the Applicant for objective evidence for nonobviousness. See MPEP 2144.08.
Furthermore, one of ordinary skill in the art would recognize from these teachings that after administration of the therapeutic agents to a subject suffering from pancreatic cancer, a decrease in the concentration of acetaldehyde, pentane, and 3-hydroxy-2-butanone would represent that the therapeutic agents are effective and conversely, an increase in the concentration of acetaldehyde, pentane, and 3-hydroxy-2-butanone would represent that the therapeutic agents are ineffective in the treatment of pancreatic cancer.
Response to Arguments
Applicant argues that Navaneethan does not disclose the analysis of VOCs in a breath sample nor does Navaneethan disclose acetoin for the diagnosis of pancreatic cancer. Since acetoin is a different type of compound from those disclosed in Navaneethan, it would not have been obvious to use acetoin in breath samples for diagnosis of pancreatic cancer.
This is not persuasive because Navaneethan clearly teaches that “breath testing is an attractive option in diagnosing patients with cancer since VOCs are present in breath samples and would represent a noninvasive diagnosis of pancreatic cancer” (pages 1042-1043). With regard to acetoin, Applicant is reminded that the secondary references were used to teach this specific limitation.
Applicant argues that Boyden and Li fail to teach acetoin for the detection of VOCs found in breath.
This is not persuasive because Boyden teach that a biomarker for diagnosing pancreatic cancer can be a C2-30 ketone, preferably a C3-14 ketone, for example acetone or 2-butanone, which is a genus of the species, acetoin. Furthermore, attention is drawn to the Song reference for the teaching of acetoin in breath samples.
Applicant argues that Song teaches the diagnosis of lung cancer, which is not relevant to pancreatic cancer. One of ordinary skill in the art would understand that different cancers have very different VOC profiles.
This is not persuasive because Song et al. teach that acetoin taken from the breath is a well-known volatile organic compound used for the early diagnosis of cancer, in general. Since acetoin is a well-known VOC, one skilled in the art would have had a reasonable expectation of success in other cancers, for example pancreatic cancer, as taught by Navaneethan and Boyden.
Applicant argues that the use of acetoin as a robust biomarker for diagnosing pancreatic cancer would not be obvious to one skilled in the art. As shown in Table 2 of the specification, acetoin was identified as the most significant VOC for pancreatic cancer. This finding came as a complete surprise and was totally unexpected.
This is not persuasive because Applicant has not sufficiently explained why or how this finding is a complete surprise or totally unexpected. In the absence of this explanation, this finding is obvious in view of the teachings of the cited prior art.
Regarding the establishment of unexpected results or synergism, a few notable principles are well settled. The Applicant has the initial burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02 (b). It is applicant’s burden to present clear and convincing factual evidence of nonobviousness or unexpected results, i.e., side-by-side comparison with the closest prior art in support of nonobviousness for the instant claimed invention over the prior art. The claims must be commensurate in the scope with any evidence of unexpected results. See MPEP 716.02 (d). With regard to synergism, a prima facie case of synergism has not been established if the data or result is not obvious. The synergism should be sufficient to overcome the obviousness, but must also be commensurate with the scope of the claims. Further, if the Applicant provides a DECLARATION UNDER 37 CFR 1.132, it must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case of obviousness. See MPEP 716.02 (e).
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623