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 .
Claims 1-16 are under examination.
Applicant’s 2/22/2024 petition for color drawings was dismissed 4/24/2025.
Applicant’s 6/24/2024 petition for color drawings was granted 7/31/2024.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains 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.
Independent claim 1 recites intranasally administering 350 U to 2000 U insulin to preterm neonates. Dependent claim 13 requires that the intranasal administration not cause systemic hypoglycemia.
Independent claim 14 recites intranasally administering 175 U to 1000 U insulin to each nare of a preterm infant (i.e. 350 U to 2000 U total).
The preterm neonates are not limited to humans and include other mammals such as primates and rodents. See at least specification paragraph [0068].
Example 3 intranasally administered insulin to P5 rats referencing the amounts administered in Example 1. Each rat received a total of 50 micrograms insulin (1.44 units of insulin). See at least specification paragraphs [0096 and 0147].
The amount of insulin administered in Example 3 is not commensurate in scope to the amounts of insulin required by the instant claims. The claimed amounts are orders of magnitude higher than the amount used in the example. The amounts required by the instant claims would not have been recognized as being suitable by those of ordinary skill in the art at the time of the effective filing date.
Note that Fan et al (U.S. Patent No. 11,931,403) administered 25 micrograms of insulin in 2.5 microliters of PBS to each naris of P10 pups (normal delivery). Each rat received 50 micrograms of intranasal insulin. See Example 1.
Talati et al. discloses administering 25 micrograms of insulin in 2.5 microliters of PBS to each naris of P10 pups (normal delivery). Each rat received 50 micrograms of intranasal insulin. See Section 2.3. Note that this is applicant’s own work. There is no disclosure of intranasally administering dosages of insulin comparable to those in the claims (350 U to 2000 U insulin).
Note that Li-Wan Fan et al. (2019, of record) administered 20 micrograms in 10 microliters of PBS applied to each of the nasal cavities (i.e. 40 micrograms total) in adult male rats (250 g). See section on animals and treatment. The forty micrograms would appear to correspond to about 1.15 U. There is no disclosure of intranasally administering dosages of insulin comparable to those in the claims (350 U to 2000 U insulin).
Shah et al. (January 2016, of record) discloses intranasally administering 20 IU or 40 IU of insulin to adult humans with Alzheimer’s disease. See section on intranasal administration on page 5. There is no disclosure of intranasally administering dosages of insulin comparable to those in the claims (350 U to 2000 U insulin).
The amounts of insulin administered in the instant claims are orders of magnitude higher than what would have been known to those of ordinary skill in the art as being therapeutic. They would have been considered an overdose. An insulin overdose may lead to very low blood glucose and result in coma or death.
Johansen et al. discloses that a median dose of 900 IU of insulin (range 26-4800 IU) resulted in insulin overdose. Prevalent complications included cerebral impairment. See at least abstract. The case reports of overdoses were for humans with a median age of 36 years (interquartile range of 12-71 years). See at least Table 1. This would indicate to one of ordinary skill in the art that these doses would also be overdoses in neonates and preterm neonates. Note that the weight of these subjects would be significantly greater than the weight of a preterm human neonate or preterm rat neonate.
Beuhler et al. discloses insulin overdoses as having a median of 40 (interquartile range, 25-60) units. See at least abstract, page 790-791 (bridging paragraph), Table 1, and Figure 1. Again, the subjects were primarily adults and not preterm neonates.
Webber et al. (U.S. Patent Application Publication 2023/0357349) indicates that 2.5 IU/kg insulin constituted an insulin overdose. See at least paragraph [0158]. At least for example, a 10 pound human baby would be approximately 4.5 kg so an insulin overdose would be 11.25 IU according to Webber et al. A more realistic weight for a preterm human neonate would be 2.5 kg. So an insulin overdose would be 6.25 IU according to Webber et al.
The specification does not demonstrate that administration of intranasal insulin in the amounts recited in the claims would have the required therapeutic benefits. In view of the prior art with respect to insulin overdose, it appears that deleterious results, including death, would have been more likely to result. The experimental results of 1.44 units cannot be extrapolated to predict therapeutic (or deleterious) effects for the claimed administration amounts of 350 U to 2000 U. In particular, the claimed dosages to administer would appear to be sufficient to cause systemic hypoglycemia. (See instant claim 13.)
The claimed methods are not enabled.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
Fan et al. (WO 2025/179292) discloses methods of the instant claims. This document claims priority to the instant application. It is not prior art against the instant claims.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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