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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection 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.
Priority
The instant application 18/552,657, filed 09/26/2023, is a 371 national stage entry of international patent application PCT/CA2022/050445, filed 03/25/2022, which claims benefit of U.S. provisional patent application No. 63/166,430, filed 03/26/2021.
Status of Application and Claims
The preliminary amendment filed 09/27/2023 is acknowledged. Claims 1, 3, 5, 7, 9, 11-12, 14, 16, and 18-19 are amended. Claim 20 is cancelled. Claim 21 is newly added. Claims 1-19 and 21 are currently pending and are examined on the merits herein.
Claim Interpretation
Claims 5, 11, 13, 15, and 17 are being interpreted as reciting Markush groups wherein a class of ingredient (i.e. “suspending agent” in claim 5, “sweetener” in claim 11) comprises a single ingredient chosen from the Markush group, or any combination of the listed ingredients. Thus, the presence of a single ingredient from the Markush group (i.e. “xanthan gum” in claim 5, “sucrose” in claim 11) within the suspension would satisfy the limitations of the claims.
Claim 18 appears to recite an inherent property of the oral veterinary suspension of claim 1. Therefore, claim 18 is being interpreted as not imparting further structural limitations to the claimed oral veterinary suspension of claim 1.
Claim 21 is written towards a method comprising generating an oral veterinary suspension and delivering the suspension to a neonatal animal. The preamble of claim 21 does not clarify the method as specifically being written towards generation of the suspension, or delivery of the suspension. Because the first step recited is the step of generating the oral veterinary suspension, claim 21 will be interpreted as a method of making an oral veterinary suspension. Because of this interpretation, the second step of delivering the suspension to a neonatal animal does not impart structural or functional limitations on the claimed method of making the suspension.
Claim Objections
Claim 18 is objected to because of the following informalities: claim 18 should recite “stable” instead of “stabile.” Appropriate correction is required.
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.
Claim 18 is 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 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 inventors, at the time the application was filed, had possession of the claimed invention.
The instant specification does not explain how the oral veterinary suspension is stable (i.e., if the suspension is chemically or physically stable), and the instant specification also fails to impart information on how long the oral veterinary suspension is stable for. Claim 18’s broad recitation of the suspension being “stable for at least one year” does not meet the written description provisions due to a lack of specific information regarding the stability of the suspension (chemical or physical) and its timeframe of stability. The specification provides no guidance as to determine whether or not this stability is chemical or physical, or what the timeframe of said stability is, which can include a hundred years due to the open-ended nature of the phrase “at least one year.” The specification provides insufficient written description to support the broad recitation encompassed by the claim.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The skilled artisan cannot envision the stability of the suspension being chemical or physical stability for any period of time beyond one year. Adequate written description requires more than a mere statement that is an inherent property of the invention. Therefore, the recitation of the inherent property of the oral suspension of claim 1 as recited in claim 18 fails to satisfy the written description provision of 35 USC § 112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.)
Claim 21 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification, while being enabling for treatment of anemia in newborn lambs and providing supplemental iron to newborn calves at specific doses of the oral veterinary suspension, does not reasonably provide enablement for prevention or treatment of any iron deficiency in any neonatal animal. 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 these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).[1]
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, relative skill level, and breadth of the claims
The instant invention is directed to a method of preventing or treating an iron deficiency in a neonatal animal.
The complex nature of the claims is greatly exacerbated by the breath of the claims. The claims encompass broad ways that an oral veterinary suspension comprising water, an iron salt that is iron fumarate, iron sulfate, or a combination thereof suspended in the water, and a suspending agent treats or prevents iron deficiency in a neonatal animal. The relative skill of those in the art is high, that of an MD or PhD.
The state and predictability of the art
The state of the art recognizes that effective amounts of ferrous sulphate reduce anemic effects in suckling animals, particularly piglets and calves; however, the state of the art recognizes specific parameters are required to achieve these results, particularly the effective amounts of ferrous sulphate administered to the neonatal animal. As illustrative of the state of the art, the examiner cites Churio, O. et al. (2019). “Use of Encapsulation Technology to Improve Efficiency of an Iron Oral Supplement to Prevent Anemia in Suckling Pigs,” Animals, 9(1), doi:10.3390/ani9010001 (PTO-892) and Eisa, A. M. A.; Elgebaly, L. S. (2010). “Effect of ferrous sulphate on haematological, biochemical and immunological parameters in neonatal calves,” Veterinaria Italiana, 46(3), 329-335 (PTO-892).
The lack of significant guidance from the specification or the prior art with regard to treating or preventing any iron deficiency in any neonatal animal makes practicing the scope of the invention unpredictable. Since the instant specification provides no limiting definition of the term “prevention”, the examiner will adopt the broadest reasonable interpretation for it. The Merriam-Webster’s Online Dictionary defines “prevent” as “to keep from happening or existing”, i.e., to completely eradicate. Similarly, since the instant specification provides no limiting definition of the term “treatment”, the examiner will adopt the broadest reasonable interpretation for it. The Merriam-Webster’s Online Dictionary defines “treatment” as “management and care to prevent, cure, ameliorate, or slow progression of a medical condition.”
The claim is thus very broad insofar as it recites treatment or prevention of any iron deficiency in any neonatal animal, i.e., management and care to prevent, cure, ameliorate, or slow progress of any iron deficiency in any neonatal animal, or the complete eradication of the same. While such treatment or prevention might theoretically be possible under strictly controlled laboratory conditions, as a practical matter it is nearly impossible to achieve in the “real world” in which patients live; complications such as rejection of the neonatal animal (i.e. vomiting, refusal to ingest), overdose, and toxicity are always a risk, particularly when the effective amount of the active ingredient is not addressed.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides specified guidance on administration of a particular dosage form of the invention to neonatal lambs and calves for demonstrable affects including increased hemoglobin values in neonatal calves and reduction (not complete eradication) of anemia in neonatal lambs (instant specification Examples 1 and 2). This guidance fails to address the complete eradication of all iron deficiency in all neonatal animals. Due to the limited guidance in the art surrounding prevention of iron deficiency in neonatal animals using oral suspensions akin to the instantly claimed suspension, one of ordinary skill would undergo undue experimentation in deducing which pharmaceutically effective amounts of the suspension should be administered to which neonatal animals for the complete treatment and prevention of iron deficiency in said neonatal animals. The principles, preferred embodiments, and modes of operation described in the specification fail to enable treatment or prevention of all iron deficiency in all neonatal animals.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed method could be predictably used to treat and prevent all iron deficiencies in all neonatal animals as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 1, 18 and 21 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.
Claims 1 and 21 both recite “an iron salt that is iron fumarate, iron sulfate, or a combination thereof suspended in the water.” It is unclear what is meant by this statement. As evidenced by Cameron, F. K. (2002). “The Solubility of Ferrous Sulphate,” ACS Publications, https://pubs.acs.org/doi/pdf/10.1021/j150310a002, ferrous sulphate (FeSO4) is soluble in water (p. 1 “Various Properties”). Therefore, FeSO4 would not naturally be “suspended” in water, and would instead be dissolved in water. It is unclear if the claimed iron salt is merely present in the water in the claimed suspension, or if the iron salt must be suspended in the water to satisfy the claim limitation; in the case of the latter, it is unclear how the iron sulfate would be suspended in the water due to its solubility in water. Therefore, any recitation of the iron salt being “suspended in the water” will be interpreted as meaning that the iron salt is present in the claimed suspension, regardless of whether the salt is suspended or dissolved in the water of the suspension.
Claim 18 recites that the oral veterinary suspension is stable for at least one year. It is unclear if this recited stability is chemical or physical stability. Furthermore, the claimed range of “at least one year” is a one-sided range with no upper limit. This range is indefinite because there is no evidence or disclosure in the instant specification as to how long the suspension is stable for, and what the time period of stability is.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 18 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 18 recites the oral veterinary suspension of claim 1, wherein the oral veterinary suspension is stable for at least one year. This is considered to be a recitation of an inherent property of the oral veterinary suspension of claim 1, and does not appear to impart further structural limitations on the composition itself; therefore, claim 18 fails to further limit the subject matter of claim 1, the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5-7, 9-14, 18 and 21 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 2009/0317488 A1 (Mehta, K. et al) published 12/24/2009 (PTO-892).
Mehta teaches a liquid suspension containing a ferrous ion-cation resin complex as active nutritional moiety or active pharmaceutical ingredient ([0069]). Mehta teaches a process of preparing an orally ingestible liquid suspension comprising reacting at least one orally ingestible ionic mineral and pharmaceutically acceptable cation exchange resin in an aqueous mixture, thereby forming an ionic mineral-ion exchange resin complex in situ, and mixing the aqueous mixture with one or more active or inactive components to form the orally ingestible liquid suspension (claim 1). Mehta teaches the iron in the formulation is delivered in an amount sufficient to treat iron deficiency, including iron deficiency anemia ([0081]). Mehta teaches aqueous suspensions of the invention may be obtained by dispersing the ionic mineral-ion exchange resin compositions in a suitable aqueous vehicle ([0049]). Mehta teaches exemplary suspending agents for use in the composition include xanthan gum ([0044]).
Mehta exemplifies the process of preparing the aqueous suspension having the following ingredients ([0098]):
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Mehta teaches the steps of the process, and explains that the process forms the ferrous resin complex in the suspension in situ ([0099]).
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) and Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). The preamble of instant claim 1 recites “an oral veterinary suspension for delivering supplemental iron to a neonatal animal,” which is considered to be an intended use of the suspension claimed in claim 1, and is not considered a limitation and is of no significance to claim construction regarding the suspension being claimed. Although the suspension of Mehta is not specifically written to be a veterinary oral suspension for delivering supplemental iron to a neonatal animal, because Mehta teaches a process of forming a suspension containing water as base, ferrous sulfate heptahydrate combined with the resin in situ to form the dispersed ferrous resin complex, and xanthan gum as suspending agent, Mehta reads on the claimed suspension comprising water, iron sulfate, and suspending agent, as recited in instant claim 1, and Mehta also reads on the claimed method of generating said suspension in instant claim 21. Furthermore, Mehta reads on the suspending agent being xanthan gum, as recited in instant claims 5 and 6. Additionally, the Examiner has converted the amount of xanthan gum present in the 500 mL suspension to be equivalent to 2.18 mg/mL for xanthan gum as suspending agent, which reads on the range for suspending agent recited in instant claim 7.
Mehta teaches that sucralose is an artificial sweetener ([0053]). Therefore, the presence of sucralose in the exemplary suspension of Mehta reads on claims 9-11. Mehta teaches the antioxidant ascorbic acid in the suspension is used to stabilize the ionic mineral, particularly to minimize conversion of ferrous iron to ferric iron ([0036]-[0037]). Thus, ascorbic acid reads on a preservative which preserves ferrous iron in the composition, and reads upon instant claims 12-13. Furthermore, the presence of vitamins A and D in the suspension reads upon instant claim 14.
Regarding the inherent property recited in claim 18, per MPEP 2112.01, “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established.” In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). As claim 1’s composition is identical to the prior art composition of Mehta, these compositions are presumed to have the same inherent properties regarding stability over the course of a year. Additionally, "[p]roducts of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Therefore, claims 1, 5-7, 9-14, 18 and 21 are anticipated by Mehta.
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 1-2, 5-18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0317488 A1 (Mehta, K. et al) published 12/24/2009 (PTO-892), as evidenced by “Concentration as %” (n.d.), e-safe-anesthesia.org. https://e-safe-anaesthesia.org/sessions/17_03/d/ELFH_Session/451/tab_627.html (PTO-892).
The teachings of Mehta, as they pertain to instant claims 1, 5-7, 9-14, 18 and 21 are addressed in the 35 U.S.C. 102(a)(1) and 102(a)(2) anticipation rejection supra.
The teachings of Mehta differ from the instantly claimed invention in that they fail to exemplify that the iron salt of the suspension is iron fumarate, as recited in instant claim 2. Additionally, Mehta fails to teach that the suspending agent is present in an amount of about 5 mg/mL, as recited in instant claim 8. Mehta also fails to exemplify that its suspension comprises one or more vitamins from a group comprising vitamin A acetate, vitamin B12, vitamin E acetate, or any combination thereof, as recited in instant claim 15. Mehta also fails to exemplify that its suspension further comprises one or more nutritional minerals, more specifically one or more nutritional minerals comprising sodium selenite, as recited in instant claims 16 and 17 respectively. It is noted that Mehta fails to explicitly teach that the method of generating a suspension comprising water, an iron salt that is iron fumarate, iron sulfate, or a combination thereof suspended in the water, and a suspending agent, also includes the step of delivering the suspension to a neonatal animal for prevention or treatment of an iron deficiency in the neonatal animal, as recited in instant claim 21. Note the Claim Interpretation section supra, which discusses that the second step of the method of claim 21, delivering the suspension to a neonatal animal, is interpreted as not imparting structural limitations on the claimed method of making the suspension.
Mehta does, however, teach other donor sources of iron may be readily selected, including a ferrous fumarate ([0017]). Mehta also teaches that the xanthan gum (suspending agent) is used in an amount from about 0.01 to about 5% w/v in the liquid formulation ([0044]). As evidenced by e-safe-anesthesia.org, to calculate w/v % from a concentration represented by mg/mL, it is appropriate to move the decimal point one space to the left. Using this formula, the Examiner calculates the exemplified amount of xanthan gum (2.18 mg/mL) to be 0.218 % w/v of the total suspension. Additionally, the Examiner calculates 5% w/v of xanthan gum to be equivalent to 50 mg/mL (5% w/v converts to 50 mg/mL when moving the decimal point one space to the right).
Mehta also teaches the body needs small quantities of trace minerals including selenium ([0016]). Mehta teaches a pediatric dosage unit of its invention including the ferrous cation exchange resin complex and further provides components selected from one or more of a group of components including vitamin B12 (1-2 mcg) and selenium in the form of sodium selenite (30-35 mcg) ([0068]).
Mehta teaches a method of treating iron deficiency anemia comprising the step of administering an effective amount of the non-toxic, orally ingestible mineral-ion exchange resin formulation (claims 30 and 31). Mehta teaches its formulation is particularly well-adapted for pediatric use (Abstract). Mehta defines pediatric as including both children and infants ([0002]). Mehta also teaches a recommended daily amount of iron for children aged 0-0.5 is 6 mg/day, and for children aged 0.5-1 is 10 mg/day ([0018]).
Regarding instant claim 2, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to substitute the ferrous sulfate heptahydrate used in the exemplified suspension of Mehta with ferrous fumarate, and arrive at the instantly claimed invention. Per MPEP 2143 I(B), simple substitution of one known element for another to obtain predictable results is prima facie obvious. The suspension of Mehta differs from instant claim 2’s invention in that its iron salt is ferrous sulfate, not ferrous fumarate. Mehta establishes that ferrous sulfate and ferrous fumarate are equivalents for the purpose of donating iron in the suspension of Mehta. Based on Mehta’s express teaching that other donor sources of iron (besides ferrous sulfate) may be readily selected from a group including ferrous fumarate, the ordinarily skilled artisan would reasonably predict that the substitution of ferrous sulfate heptahydrate with ferrous fumarate in Mehta’s suspension would yield a comparable suspension composition suitable for use as an orally ingestible treatment for iron deficiency.
Regarding instant claim 8, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to perform routine optimization on the amount of xanthan gum present in the suspension of Mehta, in order to optimize the suspension qualities. Mehta establishes that the purpose of xanthan gum is to act as suspension agent in the suspension, and exemplifies a concentration for xanthan gum of 2.18 mg/mL in its exemplary suspension, which is equivalent to 0.218% w/v. Mehta also establishes the appropriate finite concentration range for xanthan gum in its liquid suspension is between about 0.01 to about 5% w/v; the Examiner has converted the upper end of this range to be equivalent to 50 mg/mL. The ordinarily skilled artisan would have pursued routine optimization of the amount of xanthan gum within this finite, workable concentration range for xanthan gum (between at least 2.18 mg/mL and about 50 mg/mL) with a reasonable expectation of success based on the explicit teachings of Mehta which state that this concentration range is appropriate for xanthan gum within the suspension formulation. The range taught by Mehta (at least 2.18 mg/mL to about 50 mg/mL) overlaps, and thus renders obvious, the instantly claimed amount for suspending agent in instant claim 8. Furthermore, per MPEP 2133.05 II(A), differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). There is no indication in the instant specification that the claimed amount of suspending agent is critical for the instantly claimed suspension, and therefore this difference in concentration compared to Mehta will not support the claim’s patentability.
Regarding instant claims 15, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to add vitamin B12 to the suspension composition exemplified by Mehta, and arrive at the instantly claimed invention. Per MPEP 2143 I(A), combination of prior art elements according to known methods to yield predictable results is considered prima facie obvious. Mehta exemplifies a suspension comprising the elements of claim 1, and also teaches a separate oral dosage form for pediatric use within the scope of its invention which includes components selected from a group including vitamin B12. The only difference between Mehta and the instantly claimed invention of claim 15 is that the exemplified suspension of Mehta does not contain vitamin B12. One of ordinary skill in the art could have added vitamin B12 into the exemplified suspension of Mehta based on the teachings of Mehta which state that vitamin B12 is suitable for use in the dose form of the composition, particularly in the context of pediatric dosage. The ordinarily skilled artisan would have recognized that adding vitamin B12 to the suspension of Mehta would predictably result in an appropriate suspension dose form for pediatric treatment because Mehta teaches this to be an appropriate additional ingredient in its formulations containing ferrous cation exchange resin complex.
Regarding instant claims 16 and 17, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to add sodium selenite to the suspension composition exemplified by Mehta, and arrive at the instantly claimed invention. Per MPEP 2143 I(A), combination of prior art elements according to known methods to yield predictable results is considered prima facie obvious. Mehta exemplifies a suspension comprising the elements of claim 1, and also teaches a separate oral dosage form for pediatric use within the scope of its invention which includes sodium selenite. The only difference between Mehta and the instantly claimed invention of claims 16 and 17 is that the exemplified suspension of Mehta does not contain sodium selenite. One of ordinary skill in the art could have added sodium selenite into the exemplified suspension of Mehta based on the teachings of Mehta which state that sodium selenite is suitable for use in the dose form of the composition, particularly in the context of pediatric dosage. The ordinarily skilled artisan would have recognized that adding sodium selenite to the suspension of Mehta would predictably result in an appropriate suspension dose form for pediatric treatment because Mehta teaches this to be an appropriate additional ingredient in its formulations containing ferrous cation exchange resin complex.
Regarding the second (structurally and functionally non-limiting) method step of instant claim 21, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to use the suspension formed by the process exemplified by Mehta in Mehta’s method of treating iron deficiency anemia in an infant aged 0.0-0.5 or 0.5-1 years old, following Mehta’s recommended daily dosage for infants in these age ranges, and arrive at the instantly claimed invention. The Examiner notes that a human infant reads upon a neonatal animal. Mehta suggests its formulations are particularly suitable for pediatric use, and establishes recommended daily dosage ranges for infants in age range from 0 to 1 years of age. The ordinarily skilled artisan would have been motivated to use the suspension of Mehta for its intended purpose – treating iron deficiency anemia in pediatrics – with the daily recommended iron administration guidance for infants explicitly taught by Mehta. The ordinarily skilled artisan would have a reasonable expectation of success using the suspension of Mehta, at Mehta’s recommended intake amounts for iron for children ages 0-1, to treat iron deficiency in infants because Mehta explicitly states that its formulations are particularly suitable for pediatric use, which encompasses use by both infants and children.
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0317488 A1 (Mehta, K. et al) published 12/24/2009 (PTO-892), as applied to claims 1-2, 5-18 and 21 above, and further in view of US 2007/0077313 A1 (Krebs, P. J. et al) published 04/05/2007 (PTO-892).
The teachings of Mehta, as they pertain to instant claims 1-2, 5-18 and 21 are addressed supra.
The teachings of Mehta differ from the instantly claimed invention in that they fail to teach that the suspension comprises iron fumarate in an amount of about 100 mg/mL to about 400 mg/mL, more specifically in an amount of about 200 mg/mL, as recited in instant claims 3 and 4 respectively. Instead, Mehta exemplifies the use of ferrous sulfate heptahydrate in an amount of 12.45 g/500 mL, which is equivalent to 0.0249 g/mL, or 24.9 mg/mL.
Krebs teaches that ionic iron (ferrous) oral dosage forms, such as ferrous sulfate, ferrous gluconate, ferrous succinate, and ferrous fumarate, are often used because the ferrous form of iron has better absorption than the less soluble ferric form, which can precipitate out in the body; these ferrous supplements are most efficiently absorbed on an empty stomach, however, this is not tolerable for many people due to gastrointestinal side effects which can limit the amount of iron supplement that can be prescribed ([0007]). Krebs teaches that administering an oral iron supplement composition containing both ferrous iron salts and polysaccharide iron complex (PIC) provides an unexpectedly well tolerated method for treating iron deficiency anemia, and provides a composition that can be administered to a wide variety of patients, without regard to their ability to absorb iron through a particular physiological mechanism; in particular, the composition provides therapeutic blood iron levels, with unexpectedly increased tolerability, irrespective of the patient's ability to absorb iron via a particular absorption mechanism ([0010]). Krebs teaches ferrous fumarate is found to give particularly suitable results ([0019]). Krebs teaches the composition is administered in liquid or elixir form, combined with excipient including alcohol and water, at a concentration ranging from about 200 mg/mL to about 600 mg/mL of ferrous fumarate and from about 200 mg/mL to about 600 mg/mL of PIC; furthermore, those of skill in the art will understand that different concentrations of each component can be administered depending upon the degree of iron deficiency ([0030]).
It would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to incorporate ferrous fumarate in an amount from about 200 mg/mL to about 600 mg/mL and PIC from about 200 mg/mL to about 600 mg/mL into the suspension of Mehta, and arrive at the instantly claimed invention. The ordinarily skilled artisan would have been motivated to do so based on the teachings of Krebs which demonstrate that a composition comprising a combination of ferrous fumarate and PIC in these concentration ranges results in an unexpectedly well tolerated composition for treating iron deficiency anemia which is administrable to a wide variety of patients without regard to their ability to absorb iron through a particular physiological mechanism; thus, the ordinarily skilled artisan would seek to incorporate this combination of ferrous fumarate and PIC, at the designated amounts, into the oral suspension of Mehta in order to produce an oral suspension which is more tolerable and administrable to a wide patient population. The ordinarily skilled artisan would have a reasonable expectation of success adding both ferrous fumarate and PIC, in the taught concentration ranges, to the suspension of Mehta based on the fact that Krebs teaches water is a suitable excipient for the liquid or elixir form of the combination of ingredients, and water is the base of the suspension of Mehta – therefore, for at least this reason, the ordinarily skilled artisan would expect that incorporation of ferrous fumarate and PIC in these amounts into the suspension of Mehta would result in an oral liquid suspension product suitable for treating iron deficiency anemia.
Alternatively, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to combine the composition of Krebs with the suspension of Mehta and arrive at the instantly claimed invention, because both compositions are taught to be effective for the same purpose – treatment of iron deficiency anemia via oral ingestion of the compositions. Per MPEP 2144.06, "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Thus, combination of the suspension of Mehta with the liquid composition of Krebs would result in a product which comprises from about 200 mg/mL to about 600 mg/mL of ferrous fumarate, and the ordinarily skilled artisan would predict success combining the compositions for use treating iron deficiency anemia based on the fact that each individual composition present in the combination composition is known to successfully treat iron deficiency anemia. The taught amount of ferrous fumarate in Krebs overlaps, and thus renders obvious, the instantly claimed amount range for ferrous fumarate in instant claim 3, and also renders the specific amount for ferrous fumarate obvious in claim 4. Per MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0317488 A1 (Mehta, K. et al) published 12/24/2009 (PTO-892), as applied to claims 1-2, 5-18 and 21 above, and further in view of US 2,985,559 (James Coles, C. L.) published 05/23/1961 (PTO-892).
The teachings of Mehta, as they pertain to instant claims 1-18 and 21, are addressed supra. To reiterate, it would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to substitute the ferrous sulfate heptahydrate used in the exemplified suspension of Mehta with ferrous fumarate based on Mehta’s explicit suggestion to do so (see 35 U.S.C. 103 rejection over claims 1-2, 5-18 and 21 in view of Mehta supra).
The teachings of Mehta differ from the instantly claimed invention in that they fail to teach that the iron salt of the suspension has a particle size of about 25 µm to about 200 µm, as recited in instant claim 19.
James Coles teaches an aqueous suspension of ferrous fumarate in fine particulate form showing reduced tendency to agglomeration or impaction of the ferrous fumarate particles (Col. 1 lines 57-62). James Coles teaches that the invention is suitable for oral administration (Col. 1 lines 66-68). James Coles teaches the particle size of ferrous fumarate in the aqueous suspension should be as fine as possible so as to permit ready and even suspension on simple shaking, and thus thoroughly milled or micro-pulverized ferrous fumarate is preferred; the size of the ferrous fumarate particles is preferably such that substantially all of the particles are less than 50 µm (Col. 2 lines 1-11).
It would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the instantly claimed invention, to use ferrous fumarate particles that are less than 50 µm (in other words, 50 µm or less) in the oral suspension of Mehta, and arrive at the instantly claimed invention. The ordinarily skilled artisan would have been motivated to use ferrous fumarate of this size based on the teachings of James Coles which states that fine particulate form ferrous fumarate, particularly with a size of less than 50 µm, reduces tendency of the ferrous fumarate particles to agglomerate or impact when suspended in an aqueous suspension for oral administration. Additionally, this fine particle size for ferrous fumarate demonstrates ready and even suspension on simple shaking, which is preferrable for oral administration applications. The ordinarily skilled artisan would find a reasonable expectation of success in using ferrous fumarate with a particle size of less than 50 µm in the oral suspension of Mehta because Mehta suggests the use of ferrous fumarate as the iron source in the water-based suspension, and James Coles teaches similar water-based oral suspensions of ferrous fumarate which exhibit improved physical properties due to the fine particle size of the suspended ferrous fumarate. The taught particle size of ferrous fumarate in James Coles overlaps, and thus renders obvious, the instantly claimed particle size range for iron salt. Per MPEP 2144.05, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Claims 1, 5-6 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Churio, O. et al. (2019). “Use of Encapsulation Technology to Improve Efficiency of an Iron Oral Supplement to Prevent Anemia in Suckling Pigs,” Animals, 9(1), doi:10.3390/ani9010001 (PTO-892) in view of US 9737609 B2 (Vu, C. et al) published 08/22/2017 (PTO-892).
Churio teaches an encapsulated iron supplement for oral ingestion and its effects of iron nutrition status in neonatal suckling pigs (p. 1 Abstract). Churio teaches encapsulation of ferrous sulphate heptahydrate (FS) as non-heme iron source and atomized bovine erythrocytes (BE) as heme iron source encapsulated in the nucleus of maltodextrin-encapsulated microparticles (p. 2 “2.1. Material”). Churio teaches development of the encapsulated supplement by mixing both types of microparticles in a 1:1 ratio (1g of ferrous sulphate microparticle and 1g of bovine erythrocyte microparticle) and adding 3 mL of distilled water to generate a suspension which is then loaded into 10 mL syringe for administration (p. 3 “2.3. Supplement Compounding”). Churio teaches administration of the supplement to pigs by pouring the supplement into their mouths from the curved drench syringe; each piglet receives a total dose of 260 mg of iron, which is a sufficient amount to meet requirement for lactation period up to weaning at 21 days of age (p. 4 1st para). Churio teaches anti-anemic effects are achieved using four low-iron doses of the supplement when administered to the piglets, and iron deficiency anemia and its previous stages were successfully prevented (p. 1 Abstract; p. 7 4th para). Thus, Churio reads on the method of prevention of iron deficiency in a neonatal animal by generating oral veterinary suspension comprising water and iron salt (iron sulfate) suspended in the water, and delivering the oral veterinary suspension to the neonatal animal.
Churio differs from the instantly claimed invention in that Churio fails to teach the oral veterinary suspension formed in the method of claim 21 also comprises a suspending agent.
Vu teaches that oral dosage forms have stability problems associated with maintaining the active pharmaceutical ingredients in the suspension; these problems include sedimentation, creaming crystal growth (agglomeration), separation, and difficulty to redisperse to obtain original suspensions (Col. 2 lines 6-16). Vu teaches that the type of suspending agent influences the physical stability of suspensions (Col. 2 lines 21-25).
Vu teaches a synergistic blend of konjac powder and xanthan gum is used as suspending agent to suspend active pharmaceutical ingredients and improve the stability of oral pharmaceutical suspensions (Co. 2 lines 37-42). Vu teaches the synergistic blend of konjac powder and xanthan gum is used to make oral pharmaceutical suspensions for veterinary use (Col. 7 lines 65-67). Vu exemplifies the use of a base formulation for oral pharmaceutical suspensions comprising xanthan gum and konjac powder (Col. 9 Table 2). Vu teaches six different oral pharmaceutical suspensions containing differing active pharmaceutical ingredients using the synergistic combination of konjac powder and xanthan gum shows homogeneity and stability, even when stored at room temperature without shaking for 72 hours (Col. 9 lines 29-45; Col. 10 lines 53-56).
It would have been prima facie obvious for a person having ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the synergistic blend of xanthan gum and konjac powder suspending agents taught by Vu into the supplement suspension generated and used in Churio’s method of preventing iron deficiency anemia in neonatal piglets, and arrive at the instantly claimed invention. The ordinarily skilled artisan would have been motivated to incorporate the xanthan gum/konjac powder blend into the suspension of Churio because Churio’s suspension is an oral veterinary suspension which would benefit from the stabilizing effects of the suspending agent combination of Vu. The ordinarily skilled artisan would find a reasonable expectation of success adding the suspending agent combination o