DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed 13 February 2025 has been examined.
Claims 54–85 are pending. Claims 1–53 are canceled.
Benefit of Earlier Filing Date
The instant application was filed 20 October 2024; is a national stage application of PCT/US2023/066271, filed 27 April 2023, and claims the benefit of an earlier filing date of U.S. Prov. Pat. App. Serial No. 63/363,716, filed 28 April 2022. Applicant’s claim is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) received on 8 January 2025 and 29 June 2026 are acknowledged and have been considered.
The document cited in the IDS received on 29 June 2026 was lined-through because it is duplicative of the same document cited in the IDS received on 8 January 2025.
Objections to the Specification
The abstract of the disclosure is objected to because it recites legal phraseology (“comprising”); language referring to the purported merits (“inventive compounds,” “inventive lipid particles,” “inventive lipoplexes”); and language that can be implied (“Some embodiments of the invention,” “Other embodiments,” “Some embodiments,” “Further embodiments,” “Additional embodiments of the invention are also discussed herein”).
Appropriate correction is required.
For guidelines for the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
Objections to the Claims
(iv) Claim 71 is objected to because it refers to a “lipid particle component” without providing a chemical name, structure, or function that can be used to describe the subject matter. The term “component” is a nonce word that fails to connote any structural or functional information. Further, the claim states, “the lipid particle component is not a boron compound.” A claim must state what the invention is rather than what it isn’t. Examiner suggested deleting the work “component”. Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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.
(i) Claims 68 and 69 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 68 and 69 refer to compounds I-1, I-2, etc. without providing a chemical structure or formula for each compound. As a result, one of ordinary skill in the art must refer to the specification to understand what the claimed invention is. The description and the claims are separate statutory requirements. Under modern claim practice, claims must stand alone to define an invention. See MPEP2173.05(s) citing Ex parte Fressola, 27 USPQ2d 1608 (BPAI 1993).
Appropriate correction is required.
(ii) Claims 54–83 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 54 recites: “A boron compound selected from Formula (I) . . . where Formula (I) is Formula (Ia) and Formula (Ib) (emphasis added).”
Claim 63 recites: “wherein Y1 and Y2 are the same or different and are . . .”
Claim 84 is directed to a method of preparing a compound of Formula (Ia).
Claim 85 is directed to a method of preparing a compound of Formula (Ib).
It is unclear whether the claims are directed to a single boron compound or a mixture of different boron compounds because claim 54 uses the conjunction “and,” which can be interpreted to define the “boron compound” as a mixture of compounds according to Formulae (Ia) and (Ib). Further, claim 63 defines the Y1 and Y2 variables, which are variables located on the compounds of Formulae (Ia) and (Ib), respectively. Thus, claim 63 can also be interpreted to mean the “boron compound” refers to a mixture of compounds. By contrast, claims 84 and 85 describe a synthesis for the compounds of Formulae (Ia) and (Ib); those claims can only be interpreted to define the boron compound as a single compound. Accordingly, claims other than claims 84 and 85 are ambiguous because they can be interpreted as being directed to a single boron compound or to a mixture of different boron compounds.
Appropriate correction is required.
Claim Interpretation
The claims are indefinite for the reasons identified above. For the purposes of further examination, the claims will be interpreted as requiring a compound of Formula (Ia) or a compound of Formula (Ib).
Claim Rejections - 35 U.S.C. § 112
The following is a quotation 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.
(i) Claims 54–85 are rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement. The claims contain subject matter (i.e., derivatives) that was not described in the instant specification in such a way as to reasonably convey to one of ordinary skill in the art that Applicant, at the time the application was filed, had possession of the claimed invention.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), the Federal Circuit stated “the hallmark of written description is disclosure.” A specification adequately describes an invention when it “reasonably conveys to those skilled in the art the inventor had possession of the claimed subject matter as of the filing date.” (Id.). “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). In Ariad, the Federal Circuit explained what is required to meet the written description requirement:
This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar, 418 F.3d 1349, 1357–58 (Fed. Cir. 2005). Specifically, the level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. at 1359.
(Ariad, at 1351).
The written description of a genus, such as a chemical genus, “requires a precise structure, formula, [or] chemical name” of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997). The Federal Circuit commented on that case in the Ariad decision:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
(Ariad, at 1350).
The factors outlined in the above Federal Circuit cases are analyzed in turn below with respect to the claimed invention.
(A) The nature and scope of the claimed invention in view of the specification: relates generally to the chemical art and more specifically to the pharmaceutical art; and even more specifically to a compound of Formula (I), including a salt, geometric isomer, optical isomer, or derivative thereof; compositions, particles, or lipoplexes comprising the compound; methods of administering the compound; and methods of preparing the compound.
A salt, geometric isomer, or optical isomer of a compound of Formula (I) would be represented by essentially the same chemical structure as the base compound; however, a derivative implies a modification to the structure of the compound of Formula (I) and the modification may involve the deletion and/or addition of an atom or functional group that changes the structure of a compound of Formula (I).
The specification states: “In yet other embodiments, simple derivatives of the compounds (e.g., ethers, esters, or amides) which can sometimes have desirable retention and release characteristics and which may also be easily hydrolyzed by body pH, enzymes, or other suitable means, can be employed.” (Spec., ¶63). No examples of such derivatives are disclosed. No guidance is provided regarding where on the structure of Formula (I) the modification would occur to obtain such derivatives. And guidance is provided for preparing such derivatives.
(B) The extent and content of the prior art: The scope of the prior art (i.e., art discovered in Examiner’s search or cited in Applicant’s IDSs) is limited. Accordingly, Applicant’s disclosure is critical to show possession.
(C) The maturity of the science or technology: When considered as a whole, the science relevant to making and using derivatives of the compound of Formula (I) is in its infancy because the compounds are not disclosed in the application or prior art of record.
(D) The predictability of the aspect at issue: the chemical and pharmaceutical arts are generally recognized as unpredictable. In re Fisher, 427 F.2d 833, 839 (CCPA 1970). The art requires, for example, each potential drug candidate to be assessed for physiological activity. (Id.). Applications in unpredictable arts require more specific disclosures to satisfy the statutory requirement. In this case, there is no evidence suggesting the claimed invention is more predictable than the chemical and pharmaceutical arts are generally.
The question of written description
After considering the above factors and evidence discussed therein, Examiner finds the specification does not adequately describe a representative number of species for a derivative of a compound of Formula (I) or provide sufficient guidance for making such derivatives. As such, the specification does not reasonably convey to those skilled in the art that Applicant had possession of the claimed subject matter as of the filing date.
Examiner recommends deleting “derivatives thereof” from the claims.
(ii) Claims 79–83 are rejected under 35 U.S.C. § 112(a) because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” . . . These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claims is broad in scope. Claim 79 is a method comprising one or more administrations of the composition of claim 74. Claim 74 requires only a boron compound of claim 54. Claim 79 encompasses any disease. Claim 80 encompasses any type of cancer. Claim 81 encompasses any type of vaccine. Claim 82 encompasses any type of infection. Claim 83 encompasses any type of immune response. The claims therefore cover any disease, as well as certain classes of diseases (cancer, infection) that are broad on their own.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a method of administering a composition comprising a boron compound of Formula (I) to treat a disease. Accordingly, the nature of the invention is sophisticated.
The state of the prior art can be ascertained by reviewing the Background of the specification and/or relevant literature. Generally, in order to treat a disease, one of skill in the art must identify a biological target for affecting the disease, demonstrate a first drug candidate some way modulates the normal processes of the biological target, and demonstrate that a subject would benefit from such modulation without detrimental side effects. Typically, the process includes in vitro laboratory screening, in vivo testing, and clinical testing. Once that process has been successfully completed by the first drug candidate, subsequent drug candidates can benefit from the established proof of concept if a substantial correlation can be established between the first drug candidate and the subsequent drug candidates.
With respect to the instant application, Examiner is unaware of any evidence that the claimed boron compounds have therapeutic use and can be used to treat a disease.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical or veterinary medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor is limited to the preparation of the claimed boron compounds of Formula (I), compositions thereof, and properties associated with gene silencing activity. No correlation has been established between the gene silencing activity and the treatment of a specific disease.
The existence of working examples: There are no working examples demonstrating the treatment of a specific disease.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease encompassed by the claims, which is any disease. As claimed, the scope of such diseases is essentially unbound.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the claimed invention. The nature of the invention is sophisticated, the state of the prior art is not established for the claimed boron compounds, the breadth of the claims is broad in scope, the art is unpredictable, there are no working examples, and the guidance is directed to the preparation of the boron compounds of Formula (I), compositions thereof, and properties associated with gene silencing activity rather than a method of treating a disease or even an in vitro biological assay that correlates to the in vivo treatment of a disease. Accordingly, when the evidence is considered as a whole, one of ordinary skill in the art would conclude that undue experimentation would be required to practice the claimed invention.
Claim Rejections - 35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(i) Claims 54, 55, 57, 58, 61, 63, 64, and 67 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Aikawa et al., Chem. Lett. (2017), 46(3), 293–95 (“Aikawa”) [IDS].
Aikawa discloses the compound shown below, which anticipates instant formula (Ia) when:
m1 = 2;
n1 = 1; one of n2 and n3 = 0 and the other = 1;
X1 = CH2-CH2-CH2;
Y1 and Z1 = O-C(O)-;
R1 and R2 = alkyl; and
R3 and R4 = C15-alkyl.
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Claim 67 is directed to pKa, which is an inherent property of the boron compound. Because members of a Markush group (e.g., Formula (Ia)) share both structural and functional characteristics, one of ordinary skill in the art would expect the compound in Aikawa to have a pKa in the claimed range.
(ii) Claims 54, 55, 57, 58, 61, 63, 64, and 67 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Inbrahim, Faisal (2021), Electronic Theses and Dissertations, Paper 3731 (“Inbrahim”) [IDS].
Inbrahim discloses the compound shown below, which anticipates instant formula (Ia) when:
m1 = 2;
n1 = 1; one of n2 and n3 = 0 and the other = 1;
X1 = CH2-;
Y1 and Z1 = O-C(O)-;
R1 and R2 = alkyl; and
R3 and R4 = C13-alkyl.
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(Inbrahim, p.144).
Conclusion
No claims are allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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/JASON M. NOLAN/Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
