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 .
Election/Restrictions
Applicant’s response to the restriction/ election requirement from 6/26/2026 without traverse is acknowledged. Applicant has elected the invention of Group II (original claims 7-9), and as species- sickle cell disease. But has cancelled some original claims and has amended other original claims, to where all claims are now ultimately dependent on claim 7, and the only remaining claimed species of disease is sickle cell disease.
The restriction/ election requirement is hereby MADE FINAL. Claims 7, 11, 19, 21, 36, 42, 44, 46, 48, 50 and 52-54 are pending, and have been examined herewith to the extent of Applicant’s elected species of sickle cell disease, which in this case, is across the breadth of the claims.
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Claim Rejections - 35 USC § 112
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 7, 11, 19, 21, 36, 42, 44, 46, 48, 50 and 52-54 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 a method of treating and/or preventing sickle cell disease in a subject in need thereof, comprising administering to the subject a composition comprising 15-hydroxyeicosapentaenoic acid (15-HEPE) in free acid form or a pharmaceutically acceptable ester, or salt thereof, does not reasonably provide enablement for a method of treating and/or preventing sickle cell disease in a subject in need thereof, comprising administering to the subject a composition comprising a conjugate of 15-hydroxyeicosapentaenoic acid (15-HEPE). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
(1) The nature of the invention and (2) the breadth of the claims:
The invention relates to a method of treating and/or preventing sickle cell disease
and/or symptoms associated thereof in a subject in need thereof, comprising administering to the subject a composition comprising 15-hydroxyeicosapentaenoic acid (15-HEPE) in free acid form or a pharmaceutically acceptable ester, conjugate, or salt thereof.
The claims are very broad with respect to the compounds claimed, namely any and every conjugate of 15-HEPE.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
A search for “conjugates of 15-HEPE” does not return any specific references.
It is well established that "the scope of enablement various inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839 (1970).
Absent a mechanistic link between the method steps and the observed effect, the pharmaceutical and medical treatment arts are highly unpredictable. Most progress is established through empirical and anecdotal evidence as to the efficacy of certain treatments. Once a mechanistic link has been established between the method and the mechanism of action become more predictable. However, many uncertainties can still exist even when the mechanism of action is known. For example, factors such as the bioavailability, pharmacokinetic profile, and potency of a compound can still be uncertain even if it can be expected to be active in disease models. It is highly unpredictable to treat or prevent sickle cell disease with conjugates of 15-HEPE when it is uncertain what these conjugates even are.
(5) The relative skill of those in the art:
The relative skill of one in the art is expected to be high, such as that of a person with an advanced degree in medicinal chemistry or biochemistry.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification provides no teaching of any conjugates of 15-HEPE. It provides no definition of this claim term either. There is a teaching of an ester of 15-HEPE, but the claim language is clear that the term “ester” and “conjugate” are two separate terms. The term “conjugate” does not appear to be co-extensive with the term “derivative” either, because the specification teaches both of these terms, and does not define them to be a subset of one another. In this case, only “derivative” has been defined. “[0104] As used herein, “15-HEPE” refers to 15-hydroxy-eicosa-5Z,8Z,11Z,13E, 17Z-pentaenoic acid in its free acid form and/or a pharmaceutically acceptable ester, conjugate, or salt thereof, or mixtures of any of the foregoing. Similarly, as used herein, a fatty acid especially those written in short form (e.g., 15-HEPE) refers to the fatty acid in free acid form and/or a pharmaceutically acceptable ester, conjugate, or salt thereof, or mixtures of any of the foregoing, as long as the acyl group or the carbon chain portion of the molecule remains intact. The term “pharmaceutically acceptable” in the present context means that the substance in question does not produce unacceptable toxicity to the subject or interaction with other components of the composition. A “derivative” of 15-HEPE may be used instead in certain embodiments, which includes molecules where the acyl group or the carbon chain portion of the 15-HEPE molecule has one or more modifications, although it does not include any derivative compound missing the hydroxy group of 15-HEPE.”
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to no teaching in the prior art of prior of any conjugates of 15-HEPE, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
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, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7, 11, 19, 21, 36, 42, 44, 46, 48, 50 and 52-54 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/019919 A1 to Rowe et al. (“Rowe”, of record in Applicant’s IDS), and further in view of US 20210315851 A1 to Climax et al. (“Climax”).
Rowe teaches pharmaceutical compositions comprising 15-OHEPA (which is 15-HEPE), and its use in treating disorders. (Abstract). Rowe explicitly teaches that the disease that can be treated with 15-HEPE includes sickle cell disease (see page 13, line 21). Rowe provides a pharmaceutical composition comprising 15-hydroxy eicosapentaenoic acid (known as 15-OHEPA or 15-HEPE), and that it be may used for oral administration (See Abstract, page 1-Summary, lines 1-2). In some embodiments, the 15-OHEPA is in the form of a C1 -4 alkyl ester such as methyl ester or ethyl ester (p 1, summary, para 1, also p 3, lines 23-29).
Per Rowe, 15-OHEPA is a chiral molecule and may be used in the (S)- or (R)- enantiomeric form, or as a racemic mixture. Used herein, "15-OHEPA" includes all such forms, with no limitation as to stereospecifcity. In another embodiment, the 15-OHEPA comprises the (S) form : 1 5(S)-Hydroxy-(5Z,8Z,1 1 Z,13E,17Z)- eicosapentaenoic acid. (page 1, para 2).
Rowe teaches that effective amount refers to the amount of an active composition that is required to confer a therapeutic effect on the subject, and that a "therapeutically effective amount," refers to a sufficient amount of an agent or a compound being administered which will relieve to some extent one or more of the symptoms of the disease, disorder, or condition being treated (See p 14, para 1, lines 1-5). Further taught outcome of treatment is increase in RBC (red blood cells) is at least about 5%-400% compared to base line or placebo arm (p 20, (v), para 6).
Rowe teaches that the invention provides pharmaceutical compositions, for example orally deliverable compositions, comprising 15-OHEPA. In one embodiment, the compositions comprise a therapeutically effective amount of 15-OHEPA. In one embodiment, the pharmaceutical composition comprises about 0.1 % to about 99%, about 1 % to about 95%, about 5% to about 90% by weight of 15-OHEPA (See p 3, last para bridging page 4). Rowe teaches that the dosage forms include oral dosage form (p 7, last para) and includes tablets, capsules etc. (p 8, first para). The composition provides a daily dose of 15-OHEPA in an amount of about 1-10,000 mg (See p 25, para 2, lines 1-2). The composition of 15-OHEPA is present in an amount of about 50 mg to about 1000 mg (page 2, lines 3-6, claim 5). The reference also teaches that if a subject is administered 1-4 g of 15-OHEPA a day this may be up to 4 capsules each providing 1g of 15-OHEPA (page 8, para 4).
Rowe further discloses that the composition may also comprise other omega-3 fatty acids, e.g. EPA, or 15- Hydroxy eicosapentaenoic acid (15-OH EPA). Rowe further discloses varying the amounts of 15-OH EPA and 15-OHEPA, and the disclosed amounts fall within Applicant’s claimed ranges. “In various embodiments, the invention provides pharmaceutical compositions, for example orally deliverable compositions, comprising 1 5-OHEPA. In one embodiment, the compositions comprise a therapeutically effective amount of 1 5-OH EPA. In one embodiment, the pharmaceutical composition comprises about 0.1 % to about 99%, about 1 % to about 95%, about 5% to about 90% by weight of 15-OHEPA.” (p. 3).
Since the same composition is administered to a subject with the same disease in therapeutically effective amounts, it will achieve the same effect/ outcomes as in Applicant’s claims 11, 19, 21.
Although Rowe teaches the treatment of a diverse number of diseases, this is remedied by the teachings of Climax.
Climax further specifically narrows the diseases to hematological disorders, specifically sickle cell disease, and to their treatment with 15-HEPE. See, e.g., claims 1, 15 and 16.
Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Rowe and Climax with a reasonable expectation of success. The skilled artisan would have been motivated to do so since Rowe discloses Applicant’s claimed method with 15-HEPE as applicable to a broad array of diseases, to specifically disclose sickle cell diseases, and further in view of Climax, which shows more targeted treatment specifically of hematologic diseases, and sickle cell disease specifically.
Claim Rejections - 35 USC § 112
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.
Claim 46 is 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.
Claim 46 is directed to: “The method of claim 7, wherein the composition comprises no more than 10% wt. of omega-3 fatty acids other than 15-HEPE or omega-3 fatty acids other than 15-HEPE represents no more than 10% wt. of all fatty acids present in the composition.” It is unclear how the first part of the claim “wherein the composition comprises no more than 10% wt. of omega-3 fatty acids other than 15-HEPE” is any different from the second part of the claim “or omega-3 fatty acids other than 15-HEPE represents no more than 10% wt. of all fatty acids present in the composition”. The lack of proper punctuation, with multiple commas missing, add to this lack of clarity. So does the lack of proper grammar, e.g., the word “represents”, which appears to in reference not to a single compound, but to compounds, namely omega-3 fatty acids.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
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, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SVETLANA M IVANOVA/ Primary Examiner, Art Unit 1627
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