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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/03/2025 has been entered.
Claim Status
Applicants' response and amendments to the claims, filed 12/03/2025, are acknowledged and entered. Claim 13 was newly added.
Claims 1-13 are pending and under examination.
Claim Rejections - 35 USC § 112(a)
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 1-13 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.
Independent claim 1 was amended to add the limitation “…and includes no C3 or higher alcohols”. Specifically, claim 1 and claims dependent therefrom now require injecting a liquid injectable active pharmaceutical drug product that “…consists of greater than 99 percent non-fermented ethanol and includes no C3 or higher alcohols”.
It is readily apparent that the originally filed disclosure lacks support for this newly added limitation. Applicant asserts that the claim amendments “are fully supported by the Application, as filed” and that illustrative support for the amendment “can be found on page 3 of the Application as filed”. However, nowhere in the originally filed disclosure does Applicant disclose or describe that the liquid injectable active pharmaceutical drug product includes no C3 or higher alcohols. Indeed, the phrase “C3 or higher” appears nowhere in the disclosure. Neither is there any disclosure whatsoever of, e.g., propanol (C3 alcohol) or butanol (C4 alcohol), anywhere in the specification.
Accordingly, the newly added limitation “…and includes no C3 or higher alcohols” introduces New Matter into the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-7, 9-10, and 13 are rejected under 35 U.S.C. 103(a) as being unpatentable over FABER ET AL. (Circulation, 1998, vol. 98, p.2415-2421), KNIGHT (Heart, 2006, vol. 92, p.1339-1344), and NISHIMURA ET AL. (Circ. Res., 2017, vol. 121, p.771-783) in view of PHARMCO (“Product Specifications Sheet, Harmonized USP/BP/EP/JP Alcohol, Absolute, Dehydrated, Anhydrous (200 PROOF), Pure ETHANOL”, 2017) and ITW REAGENTS (“Ethanol absolute (USP, BP, Ph.Eur.) pharma grade”, 2017, Technical Data Sheet, Product Code: 191086, 3 pages) (Accessed from https://www.itwreagents.com/download_file/tds/191086/en/tds_191086_en.pdf).
The claims circumscribe a method of reducing septal thickness in a patient comprising a series of steps wherein a liquid injectable active pharmaceutical ingredient drug product consisting of greater than 99% non-fermented ethanol is injected into a target septal artery.
FABER ET AL. teach percutaneous transluminal septal myocardial ablation (PTSMA) has been introduced as an alternative procedure for reducing the left ventricular outflow tract gradient (LVOTG) in hypertrophic obstructive cardiomyopathy (Abstract). Regarding claims 7 and 10, they teach measuring left ventricular outflow tract gradient (LVOTG) (“[a]ortic pressure was monitored by the percutaneous transluminal coronary angioplasty guiding catheter after exclusion of an aortic valve gradient…LVOTG was assessed at rest and after a premature ventricular beat”) (p.2416, paragraph bridging left and right columns). Regarding claim 6, they teach all patients received a 4F transfemoral pacemaker lead introduced into the right ventricular apical region (Id.). They teach the presumed target vessel was then selectively intubated with a 0.014-inch guide wire through a 7F or 8F percutaneous transluminal coronary angioplasty guiding catheter. A short, slightly oversized over-the-wire balloon (1.5 to 3.0 mm) was introduced and inflated, and the distal vessel bed was contrasted. After exclusion of dye reflux into the left anterior descending coronary artery (LAD), and if probatory vessel closure by the inflated balloon had resulted in significant LVOTG reduction, the alcohol was injected in fractions of 1 mL in the first 30 patients (p.2416, right column, first full paragraph). They teach the balloon remained inflated for 10 minutes after the alcohol administration to enhance tissue contact and to exclude alcohol reflux into the LAD (p.2416, right column, third full paragraph).
KNIGHT also sets forth the well-known method steps for the alcohol septal ablation procedure. He teaches a guiding catheter is introduced into the left main coronary artery and a 0.014 inch guidewire into the left anterior descending artery (LAD). The first septal artery is usually selected, and a short (~10 mm) ‘‘over the wire’’ (OTW) balloon introduced into the branch. The lumen of this device provides the route for delivery of angiographic contrast, echo contrast, and ultimately alcohol, selectively into the septal artery. As transient heart block is common at the time of injection, a temporary pacing wire is routinely inserted, usually via the femoral vein. As required by claims 7 and 9, the OTW balloon is positioned under fluoroscopic guidance to ensure that it is entirely within the septal branch and does not encroach on the lumen of the LAD. The OTW balloon is inflated and the guidewire removed. A small amount of angiographic contrast is injected through the OTW balloon to ensure that there is no spill back into the LAD. An echocardiographic contrast agent is then injected through the OTW balloon. Absolute alcohol (1–2 ml) is administered slowly through the lumen of the OTW balloon, with the balloon remaining inflated for five minutes. See p.1340-1341, “Alcohol Septal Ablation: The Procedure”.
NISHIMURA ET AL. also sets forth the known method steps for the alcohol septal ablation procedure. They teach before the ablation, an initial diagnostic catheterization
to measure the left ventricular outflow tract is performed. They teach a temporary pacemaker lead should be inserted in patients without a permanent pacemaker or ICD in place. A guidewire is advanced into the target septal artery; an over-the-wire balloon is then advanced into the target septal artery and inflated to avoid backflow of alcohol into the left anterior descending artery, thereby avoiding infarction of nontarget myocardial areas. After the guidewire is withdrawn, echocardiographic contrast agent is injected through the balloon catheter with simultaneous transthoracic echocardiography. Up to 3 mL of absolute alcohol is then injected slowly through the central lumen of the balloon catheter under continuous fluoroscopic, hemodynamic, and electrocardiographic observation. After withdrawal of the balloon catheter, a final angiogram
is performed to document complete occlusion of the septal branch and normal flow in the left anterior descending artery. See p.778, left and right columns, “Procedure”.
The combined teachings of Faber et al., Knight, and Nishimura et al. differ from the claimed invention only in so far as they do not expressly teach that the alcohol utilized in the alcohol septal ablation procedure taught therein consists of greater than 99% non-fermented ethanol. Rather, they teach injecting “absolute alcohol”.
It would have been obvious at the time the application was filed to utilize the highest purity ethanol available to carry out alcohol septal ablation as taught in the cited prior art. A person of ordinary skill in the art would obviously seek to minimize impurities and contaminants in any drug product administered to human patients. In this regard, absolute ethanol containing ≥99% (v/v) ethanol was readily available to those skilled in the art before Applicant’s filing date. See, for example, PHARMCO (“Product Specifications Sheet, Harmonized USP/BP/EP/JP Alcohol, Absolute, Dehydrated, Anhydrous (200 PROOF), Pure ETHANOL,”), which teaches grain-derived Absolute, Dehydrated, Anhydrous ethanol that is no less than 99.5% pure (typically 99.99%). It teaches that the “typical result” for tests for impurities are: <5 ppm for methanol, “None Detected” for acetaldehyde, acetal, and benzene, and <10 ppm “Sum of all other impurities”. Indeed, “pharma grade” absolute ethanol was also known and commercially available in the art (ITW REAGENTS). This “pharma grade” absolute ethanol is minimum 99.5% pure and contains less than 0.0002% benzene, less than 0.001% acetaldehyde and acetal, and less than 0.03% total of “other impurities”. Regarding the newly added limitation “…and includes no C3 or higher alcohols”, neither PHARMCO nor ITW REAGENTS names C3 or higher alcohols (e.g., propanol or butanol) as impurities present in their ethanol products.
Applicants recite the use of a drug product that consists of “greater than 99 percent non-fermented ethanol” (Claim 1) and newly added dependent claim 13 recites that the drug product is “produced by hydration of ethylene”. There is no factual evidence of record that the source or method of making high-purity ethanol leads to any meaningful difference in the final product. Put another way, Absolute, Dehydrated, Anhydrous ethanol that is no less than 99.5% pure is Absolute, Dehydrated, Anhydrous ethanol that is no less than 99.5% pure whether it is grain-derived ethanol such as taught in PHARMCO or other such high-purity ethanol products known in the art such as the “pharma grade” absolute ethanol taught in ITW REAGENTS or “non-fermented ethanol” as presently claimed. Ethanol is ethanol, whether it is made by fermentation or synthetically, i.e., it has the same chemical formula (C2H6O), molecular weight, and physical/chemical properties. Thus, ≥99% grain-derived, fermented ethanol is chemically and physically identical to ≥99% non-fermented ethanol, absent factual evidence to the contrary. For example, Applicant has still proffered no factual evidence that the claimed “non-fermented ethanol”, e.g., ethanol produced by hydration of ethylene, does not contain the same impurities present in fermented alcohol and/or has any different chemical, physical, or biological properties from ≥99% grain-derived, fermented ethanol.
Accordingly, it would have been prima facie obvious to a person of ordinary skill in the art to administer absolute ethanol containing ≥99% (v/v) ethanol in the alcohol septal ablation taught in the cited prior art, regardless of whether or not that absolute ethanol containing ≥99% (v/v) ethanol was made by fermentation or not.
Claim(s) 8 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over FABER ET AL. (Circulation, 1998, vol. 98, p.2415-2421), KNIGHT (Heart, 2006, vol. 92, p.1339-1344), and NISHIMURA ET AL. (Circ. Res., 2017, vol. 121, p.771-783) in view of PHARMCO (“Product Specifications Sheet, Harmonized USP/BP/EP/JP Alcohol, Absolute, Dehydrated, Anhydrous (200 PROOF), Pure ETHANOL”, 2017) and ITW REAGENTS (“Ethanol absolute (USP, BP, Ph.Eur.) pharma grade”, 2017, Technical Data Sheet, Product Code: 191086, 3 pages) (Accessed from https://www.itwreagents.com/download_file/tds/191086/en/tds_191086_en.pdf) as applied to claims 1-7, 9-10, and 13 above, and further in view of RAZAVI ET AL. (The Lancet, December 6, 2003, vol. 362, p.1877-1882) and SITGES ET AL. (Catheterization and Cardiovascular Interventions, 2001, vol. 53, p.524 –526).
The teachings of Faber et al., Knight, Nishimura et al., Pharmco, and ITW Reagents as applied to claims 1-7, 9-10, and 13 supra are incorporated by reference in their entirety and applied equally to claims 8 and 11-12. Claims 8 and 11-12 differ from the combined teachings of Faber et al., Knight, Nishimura et al., Pharmco, and ITW Reagents in so far as the references, while disclosing guiding a catheter by fluoroscopy, do not disclose guiding the catheter used for alcohol ablation by echocardiogram or MRI. However, as evidenced by the following prior art such means of guidance were well-known and routine in the art of alcohol ablation.
RAZAVI ET AL. teach fluoroscopically guided cardiac catheterization is an essential tool for diagnosis and treatment of congenital heart disease but has drawbacks. They describe a novel method of cardiac catherization guided by MRI with radiographic support (p.1877, left column, “Background”). They teach advancing the catheter using either MRI guidance with real time sequences or with a combination of fluoroscopic and MRI guidance depending on ease of catheter manipulation (p.1879, paragraph bridging left and right columns). They teach MRI guidance for cardiac catheterisation affords greater physiological and anatomical information than do other methods (p.1881, right column, first full paragraph; Table 4).
SITGES ET AL. teach treating a patient with a percutaneous transluminal septal myocardial ablation (PTSMA) (p.524, left column, “Introduction), wherein the left coronary artery was catheterized following a standard procedure and ethanol 3 cc was infused in the first septal branch of the left anterior descending artery. A transesophageal echocardiogram was performed with myocardial contrast imaging to determine the correct septal branch for the alcohol injection (p.524, right column, second full paragraph).
The Examiner’s rationale and conclusion of obviousness as applied to claims 1-7, 9-10, and 13 supra is incorporated by reference and applied equally to claims 8 and 11-12. With specific regard to claims 8 and 11-12, it would have been obvious to a person of ordinary skill in the art that catheter guidance in percutaneous transluminal septal myocardial ablation could be readily and predictably achieved through the use of echocardiography, fluoroscopy, or cardiac MRI with or without contrast as such means for catheter guidance in cardiac procedures was well-known and routine in the art as evidenced by the cited prior art. The application thereof in alcohol septal ablation procedures as taught by the cited prior art would predictably identify the desired location in the heart for the catheter as demonstrated by the combined teachings of the cited prior art.
Response to Arguments
Applicants argue:
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In response, Applicants still have not presented any factual evidence that “non-fermented ethanol” possesses any enhanced/unexpected characteristics relative to fermented alcohol. Regardless of any impurities that may or may not be present, ethanol is ethanol and it is the ethanol that is providing the therapeutic benefit in patients. Furthermore, despite Applicant’s assertions to the contrary, purified and rectified ethanol produced by fermentation IS in fact chemically identical to purified and rectified non-fermented ethanol. It still has the molecular formula CH3CH2OH. Just because it might have different impurities present doesn’t change the chemical composition of the ethanol per se. As has been repeatedly explained by the Examiner, physically, chemically, and biologically, Absolute, Dehydrated, Anhydrous ethanol that is no less than 99.5% pure (typically 99.99%) would be expected to have the same properties whether produced by fermentation or not. The end product, i.e., ethanol, is physically, chemically, and biologically the same, i.e., it is ethanol, absent factual evidence to the contrary. Applicant’s arguments that the presence of small, insignificant amounts of impurities somehow dramatically change the physical, chemical, and/or biological properties of the ethanol are unavailing and defy common sense. To this point, the Examiner maintains that those skilled in the art routinely used absolute ethanol as an active pharmaceutical ingredient as evidenced by the cited prior art. Applicants clearly did not invent reducing septal thickness in a patient by injecting ethanol through a catheter into a septal artery. As evidenced by at least ITW REAGENTS “pharma grade” absolute ethanol was readily available for such a purpose prior to the filing of Applicant’s application. The Examiner maintains that Applicant still has yet to provide any factual evidence that “greater than 99 percent non-fermented ethanol” has any physical, chemical, or biological properties that the >99.5% pure fermented absolute ethanol taught in the prior art doesn’t have.
Similar to “product-by-process” claims, it is the end product that is evaluated for patentability, not the process by which it is made. Such is the case here – the prior art teaches all of the limitations of the claimed method, but does not expressly disclose how the “absolute ethanol” used in the method was made. It is the position of the Examiner that, similar to a product-by-process claim limitation, the claimed “non-fermented alcohol” is physically, chemically, and biologically the same as grain-derived ethanol absent factual evidence to the contrary.
A similar fact pattern was recently evaluated by the U.S. Court of Appeals for the Federal Circuit (“CAFC”) where they reviewed the patentability of a product-by-process limitation embedded within a method claim. See Biogen MA, Inc. v. EMD Serono, Inc., F.3d, 2020 WL 5755468 (Fed. Cir. Sept. 28, 2020). The main claim in Biogen’s patent recited a method for immunomodulation or treating a condition or disease “comprising the step of administering to a patient in need of such treatment a therapeutically effective amount of a composition comprising a recombinant polypeptide produced by non-human host transformed by a recombinant DNA molecule. . .” The CAFC reconfirmed its own prior precedent that the “nesting of a product-by-process limitation within a method of treatment claim does not change the construction of the product-by-process limitation itself.” The Court explained that there “is no logical reason why the nesting of a product-by-process limitation within a method claim should change how novelty of that limitation is evaluated.” Such is the case here, where the novelty/non-obviousness of the claimed method rests wholly on the novelty/non-obviousness of the composition administered – a product-by-process, which should be determined by comparing the ethanol of the claim with the prior art ethanol – not by comparing the process of forming it. In this case, Applicant has failed to provide factual evidence that the claimed non-fermented ethanol possesses any physical, chemical, or biological properties different from fermented ethanol.
Conclusion
Claims 1-13 are rejected.
Applicant is requested to specifically point out the support for any amendments made to the disclosure in response to this Office action, including the claims (M.P.E.P. §§ 714.02 and 2163.06). In doing so, applicant is requested to refer to pages and line (or paragraph) numbers (if available) in the as-filed specification, not the published application. Due to the procedure outlined in M.P.E.P. § 2163.06 for interpreting claims, other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Applicant is reminded that MPEP §2001.06(b) clearly states that “[t]he individuals covered by 37 C.F.R. 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question." See Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972). MPEP §2001.06(b) clearly indicates that “if a particular inventor has different applications pending in which similar subject matter but patentably indistinct claims are present that fact must be disclosed to the examiner of each of the involved applications.” See Dayco Prod. Inc. v. Total Containment, Inc., 329 F.3d 1358, 1365-69, 66 USPQ2d 1801, 1806-08 (Fed. Cir. 2003).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES D ANDERSON whose telephone number is (571)272-9038. The examiner can normally be reached on Monday-Friday, 7:30 am - 4:00 pm PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/James D. Anderson/Primary Examiner, Art Unit 1629
UNITED STATES PATENT AND TRADEMARK OFFICE
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Tel. No.: (571) 272-9038