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 election without traverse of group I, and species of compound IV-a as shown in ¶ [0067] of the specification, oral administration and the gastro-intestinal tract in the reply filed on July 7, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
The elected species has variables of R1 and R2 together with the nitrogen to which they are attached forming a reside of general formula (III), with one of R3 and R4 being H and the other being the sugar residue with R5 being a hydrogen and is also known by the common name betanin.
Claim Interpretation
Claims 22 and 24 define the process by which the composition administered in claim 12 is produced. The nesting of the product-by-process limitation within a method of treat ment claim does not change the proper construction of the product-by-process limitation itself.
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) MPEP 2113.
Particularly given the optional step of the addition of betanin and/or vulgaxanthin, compositions comprising such ingredients fall within the scope of the product produced by the process of claim 22. Ozonation can alter the product that is produced by the recited process and that is reflected in the rejections set forth below.
Claim Rejections - 35 USC § 112 – Scope of Enablement
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.
Claim 24 is 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 the use of compositions that comprise sufficient intact betalains to act as a contrast agent as required by the method of claim 12, does not reasonably provide enablement for all compositions comprising one or more chemically distinct betalains that are ozonized. 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 disclosure and claims of the application have been compared per the factors indicated in the decision In re Wands, 8 USPQ2nd 1400 (Fed. Cir. 1988) as to undue experimentation
The factors include:
1. The nature of the invention;
2. The breadth of the claims;
3. The predictability or unpredictability of the art;
4. The amount of direction or guidance presented;
5. The presence or absence of working examples
6. The quantity of experimentation necessary;
7. The state of the prior art; and
8. The relative skill of those skilled in the art.
Each relevant factor is addressed below on the basis of comparison of the disclosure, the claims and the state of the art in the assessment of undue experimentation.
The nature of the invention; the breadth of the claims:
The claims are drawn to a method of acquiring a contrast enhanced image using magnetic resonance imaging (MRI) of a subject in which a composition comprising one of more chemically distinct betalains, the contrast agent, and water is administered to a subject and then an image of the subject is acquired using MRI. The compositions can be administered via various routes for imaging of different parts of the body.
The predictability or unpredictability of the art; the amount of direction or guidance presented; the presence or absence of working examples; the quantity of experimentation necessary; the state of the prior art; the relative skill of those skilled in the art:
The relative skill of those skilled in the art is relatively high such as research scientist or technician who routinely acquires images using techniques such as MRI.
The claims do not merely require the acquisition of any MRI image but one that is contrast enhanced, which is accomplished by administration of a contrast agent, in this case, one or more chemically distinct betalains.
Ozonization is the exposure of, in the instant claim, the composition comprising the one or more chemically distinct betalains and water to ozone, a strong oxidant. As discussed in Sadowska-Bartosz et al. (Molecules, 2021), betalains react with molecular oxygen with aerobic oxidation of betacyanidins, a genus which includes betanin (see Figure 1a), is mediated by reactive oxygen species (p 10, ¶¶ 2 and 3). The hydrolysis of betanin glycosides and release of aglycones, which are themselves more labile and prone to oxidation that causes a bathochromic shift of 4–6 nm (p 11, ¶ 1). While slightly different in structure than betalains (see figure 1), reduction in the fluorescence of betaxanthins serves as a measure of betaxanthin oxidation (p 6, ¶ 6). Therefore one of ordinary skill in the art would reasonably expect that upon exposure of a composition to comprising betalains to ozone, the betalains would be oxidized, altering their structure and properties. Ozonization of oils for is known, but based on the description of Aydm et al. (introduction section on p 1385; J Am Oil Chem Soc, 2018) it appears that oxidizing species are present in the final product so if such materials are contacted with the betalain containing compositions, the same degradation of the betalain along with alteration in function could occur.
While the specification generally discloses that the oil and/or oil containing compositions can be ozonized, no examples of contrast enhanced images appear to have been generated to demonstrate with such a composition to demonstrate that such a compositions retain the ability to enhance the contrast during an MRI. Undue experimentation would be required to determine the structure of the betalain(s) and/or other conditions such as concentration or protective ingredients such as antioxidants that might be required to preserve the ability of the betalain containing composition to still generate a contrast enhanced image using MRI when either the composition as a whole or ingredients of the compositions were ozonized.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 12 – 14 and 17 – 25 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.
Claim 12, from which all other claims depend, requires a composition comprising “one or more chemically distinct betalains” (emphasis added) and it not clear what the requirements are for chemical distinctness are. The claims do not use the common phrasing of “one or more betalains” that would indicate that any betalain, alone or in combination with other compounds also falling within the genus of betalains must be present in the claimed composition. Structural isomers are compounds that differ in the connectivity of the atoms but have the same molecular formula. For example, multiple sugars such as glucose, fructose, galactose and mannose all have the same molecular formula or can comprise an aldehyde or ketone, which are distinct functional groups. Are structural isomers considered to be chemically distinct even though they have the same molecular formula? Stereoisomers not have the same molecular formula but the same sequence of bonded atoms but differ in the 3-D orientation of those groups. Are stereoisomers considered to be chemically distinct due to the difference in 3-D structure? Therefore the scope of what would read on more than one chemically distinct betalain cannot be determined.
The dependent claims fall therewith.
Please clarify.
Claim 19 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 19 depends from claim 2 which has been cancelled for the definitions of R3 and R4. Therefore the metes and bounds of this claim cannot be determined. Please clarify.
In the interest of compact prosecution, this claim is being examined to the extent that it reads on the elected species. Upon clarification of the scope of this claim, the examination status of this claim will be reevaluated.
Claim 23 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. Regarding claim 23, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Please clarify.
Claim Rejections - 35 USC § 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.
Claim(s) 12 – 14, 17 – 19, 21 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arthurs et al. (BMC Medical Imaging, 2014) as evidenced by Chhikara et al. (Food Chem, 2019).
Arthurs et al. discloses the use of various juices, including a mixture of beet juice and apple juice (whole document, e.g. title and Table 1). For the in vivo experiments, the juice was orally administered (p 4, col 1, ¶ 2) and interactive MRI in vivo was performed using an IR-SSFSE pulse sequence (p 3, col 1, ¶ 4) to generate images such as those shown in figure 4 that are used to visualize the gastrointestinal tract (e.g., abstract).
When a species is clearly named, the species claim is anticipated no matter how many other species are additionally named (MPEP 2131.02(II)).
That the beet juice of Arthurs et al. comprises one or more betalains is not explicitly taught. However, Chhikara et al. evidences that the beet juice will comprise at least one betalain such as betanin as beetroot is one of the richest sources of betanin along with other betacyanins including prebetanin, isobetanin and neobetanin (p 194, col 2, ¶ 3). The first paragraph of column 2 on p 195 indicates a concentration of 312.5 mg betanin per 100 g of pressed juice from beetroot.
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.
Claim(s) 12 – 14, 17 – 22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Arthurs et al. (BMC Medical Imaging, 2014) as evidenced by Chhikara et al. (Food Chem, 2019).
Arthurs et al. and Chhikara et al. are discussed above.
The concentration of ingredients such as the betalains of beet juice including betanin used as a contrast agent were not explicitly disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to select various fruit juices such as the beet juice containing composition of Arthurs et al. for oral administration to a subject to generate contrast before acquisition of an image of gastrointestinal tract using MRI. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the beet juice containing composition does generate contrast and depending on the availability of various materials, potential allergies of the patient being imaged and the imaging parameters used, one of ordinary skill in the art would routinely optimize the material being used. The material used was a mixture of apple and beet juice so routine optimization by one of ordinary skill in the art would also include determining the optimal amount of the different juices that contain betanin, beet juice being a particularly rich source of this betalain, and there is no evidence of record as to the criticality of the claimed concentrations of the betalain when used as a contrast agent.
Claim(s) 23 is rejected under 35 U.S.C. 103 as being unpatentable over Arthurs et al. and Chhikara et al. as applied to claims 12 – 14, 17 – 22 and 25 above, and further in view of Kaimainen et al. (LWT Food Sci and Tech, 2015) and Brito De La Fuente et al. (US 2018/0000732).
Arthurs et al. and Chhikara et al. are discussed above.
The presence of olive oil in the composition is not disclosed.
Kaimainen et al. discloses that betalains are water-soluble but sensitive to high temperature, basic or very acidic pH, light, air (oxygen) and high water activity (¶ bridging cols 1 and 2 on p 899). Their stability could be improved by encapsulation technologies such as emulsification (p 899, col 2, ¶ 1) and since most foods have an aqueous continuous phase, w/o/w (water in oil in water) double emulsions have more potential as they offer the possibility to incorporate both lipophilic and hydrophilic compounds (p 899, col 2, ¶ 2). Double emulsions have also been extensively studied for drug industries (p 899, col 2, ¶ 2). As shown in figure 5 and discussed in section 3.4, the betalain encapsulated in the double emulsion showed a time dependent release profile with fast release during the first 120 minutes that slowed until no further release was observed after 180 minutes (¶ bridging p 902 and 903).
Brito De La Fuente et al. discloses oil-in-water emulsions for parenteral administration (whole document, e.g., abstract). A variety of oils can be used in the preparation of the emulsion, including olive oil which is among the preferred oils disclosed (¶¶ [0032] and [0033]). Various amounts for the oil phase are disclosed at ¶ [0029] and can be from 2 – 30 wt% of oil phase.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate the beet juice and active agents contained therein using the w/o/w emulsion disclosed by Kaimainen et al. and to use olive oil for the oil phase of the emulsion that is then used as a contrast agent with MRI. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Kaimainen et al. discloses that betalains are water soluble and their stability can be improved by encapsulation in a w/o/w emulsion, that are known for food and drug uses, while also providing a sustained release. This can add additional functionality to the imaging process as images obtained shortly after oral administration would reflect the intact gastrointestinal system before much release had occurred. As betalains were released, potentially more information about where the material traveled over time could be collected. Olive oil in a known oil for use in emulations to be parenterally administered and the selection of oils known for use in emulsions is prima facie obvious absent evidence of criticality. “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05.
Claim(s) 24 is rejected under 35 U.S.C. 103 as being unpatentable over Arthurs et al., Chhikara et al., Kaimainen et al. and Brito De La Fuente et al. as applied to claims 12 – 14, 17 – 23 and 25 above, and further in view of Aydm et al. (J Am Oil Chem Soc, 2018).
Arthurs et al., Chhikara et al., Kaimainen et al. and Brito De La Fuente et al. are discussed above.
The use of ozonated materials is not disclosed.
Aydm et al. discloses that ozonation of unsaturated oils improves the stability of ozone and such materials have been shown to have beneficial effects on wound healing, antibacterial activity and will slowly release ozone over time (¶ bridging p 1385 and 1386). Ozonated olive oil was used to prepare nanoemulsions (p 1386, col 2, ¶¶ 1 and 2).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use an ozonated material at least as an antimicrobial agent that can act as a preservative for the emulsion even if other properties such as enhanced wound healing are not needed for all imaging applications of the betalain containing emulsion administered for imaging purposes. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because ozonated oils such as olive oils can be used in emulsions as taught by Aydm et al. and impart beneficial effects such as antibacterial activity and enhanced wound healing. It would be obvious to one of ordinary skill in the art to vary the order of steps because, in such a method, where the order of steps is not critical, one of ordinary skill in the art would have recognized that varying the order of steps would result in an equivalent means of carrying out the method as to whether the oil was ozonated prior to being made into an emulsion or the composition as a while was ozonated after preparation of the emulsion.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Nissa M Westerberg/Primary Examiner, Art Unit 1618
Prosecution Insights