DETAILED ACTION
Status of Claims
The amendment filed 06/02/2026 is acknowledged. Claims 1, 3, 4, 10, 11, 16, and 20 are currently amended. Claim 2 is Cancelled. Claims 1 and 3-20 are pending and under examination.
Withdrawn Rejections/Objections
The rejection of claims 10 and 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the claims being amended to omit the indefinite language.
The rejection of claims 1 and 10 under 35 U.S.C. 102 as being anticipated by NIH Grant 1I21RX001371-01 is withdrawn in view of the amendment to claim 1 to include the limitation of “wherein the subject suffers from hypogonadotropic hypogonadism (HH).”
The rejection of claims 1, 7, 8, 11, and 16 under 35 U.S.C. 102 as being anticipated Zygun et al. is withdrawn in view of the amendment to claim 1 to include the limitation of “wherein the subject suffers from hypogonadotropic hypogonadism (HH).”
The rejection of claims 1, 5, 10, and 15 under 35 U.S.C. 102 as being obvious over NIH Grant 1I21RX001371-01 is withdrawn in view of the amendment to claim 1 to include the limitation of “wherein the subject suffers from HH.”
Maintained/Modified Rejections
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 16 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
In the context of claim 16, the phrase “optionally” reads as an exemplary term. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP 2173.05(d).
Therefore, claim 16 is rejected under 35 U.S.C. 112(b) for being indefinite.
Claims 1, 3-5, 10, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over NIH Grant 1I21RX001371-01, in view of Barton et al.
Claims 1, 3-5, 10, and 15 are drawn to a method of treating traumatic brain injury (TBI) induced hypogonadal hypogonadism (HH).
1I21RX001371-01 discloses administering hCG to subjects suffering from TBI to enhance neurogenesis and stimulate cognitive recovery (claim 1), and that subjects would be treated for 6 months (claim 10) [see Specific Aim 1].
1I21RX001371-01 does not teach or suggest a method wherein the subject suffers from HH, a TBI-associated impairment induced by an injury to the hypothalamus or pituitary gland, or impairment induced by suppression of synthesis and secretion of hormones produced by the hypothalamic-pituitary-gonadal (HPG) axis. 1I21RX001371-01 also does not teach or suggest the specific sequences disclosed in claim 5, or sequences having 90% identity thereto, nor does it teach or suggest that the subjects are capable of normal adult gonadal hormone synthesis and secretion.
Barton et al. discloses that individuals suffering from TBI frequently develop HH [see p.2 paragraph 1] (claim 1), which is characterized by low testosterone levels [see p.2 Introduction] and/or low or inappropriately normal gonadotropin levels [see p.7 paragraph 4], demonstrating dysfunction of the HPG axis (claim 4). Further, Barton et al. explains that HH frequently results from damage to the pituitary gland [p. 8 paragraph 1] (claim 3).
It would have been obvious to combine the disclosure of 1I21RX001371-01 of administering hCG to subjects suffering from TBI with the teachings of Barton et al. as a means to restore gonadal hormone function in individuals with a pituitary gland injury or impaired HCG axis following TBI because the art teaches that HH is a common consequence of TBI and results from damage to the pituitary and/or from an impaired HCG axis (claims 1, 3, and 4). Furthermore, there would be a reasonable expectation of success as one would reasonably believe that administering hCG to TBI patients with HH, which is also characterized by low gonadotrophin levels, would have the effect of stimulating the gonads to produce normal gonadal hormones, thereby inducing neurogenesis and improving cognitive outcomes as taught by 1I21RX001371-01.
Regarding claim 15, 1I21RX001371-01 does not limit administration to subjects exhibiting hypogonadism nor does it exclude subjects having normal circulating gonadal hormone levels. Thus, because 1I21RX001371-01 administers hCG broadly to TBI subjects without limitation based on hormonal status, one would reasonably assume that the subject population encompasses TBI subjects having normal gonadal hormone levels, and selecting this subset of subjects from the broader population would have been obvious without evidence that hormonally normal subjects would respond differently (claim 15).
Regarding claim 5, the sequences recited encode the native human alpha and beta subunits of hCG and hLH. hCG and hLH are well characterized proteins with subunit sequences that were publicly known at the time of the invention. More specifically, SEQ ID NO: 1 was available as of May, 2009 [see UniprotKB: C0KRQ8], SEQ ID NO: 2 as of July, 2015 [see UniprotKB: A0A0F7RQP8] and SEQ ID NO: 3 as of March 2002 [see UniprotKB: Q8WXL0]. It would have been obvious to use the native alpha and beta subunits in the modified method of 1I21RX001371-01 as it was routine in clinical and experimental practice to do so (claim 5).
Therefore, claims 1, 3-5, 10, and 15 are rejected under 35 U.S.C. 103.
Claims 1, 3-5, 7, 8, 11, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Zygun et al. in view of Barton et al.
Claims 1, 3-5, 7, 8, 11, 15, and 16 are drawn to a method of treating TBI induced HH.
Zygun et al. discloses administration of hCG every other day for a total of 3 doses [see p. 8, Intervention/treatment], which is equivalent to every other day for one week (claims 7 and 8), to male patients ages 18-65 [see p. 5, Inclusion Criteria, point 1; p. 8, Intervention/treatment] and to women “of child bearing potential,” [see p.5, Inclusion Criteria, point 6-2] which encompasses pre-menopausal women (claim 16), following TBI [see p.5, Inclusion Criteria, point 3] (claim 1). Zygun et al. further discloses administration of hCG at 10,000 IU per dose. CDC health statistics using data gathered from 2015-2018 estimate that the average woman’s weight in the United States during that time was about 76kg [see p.7] and about 90kg for men [see p.9]. This corresponds to about 130 IU/kg to for human female subjects and 111 IU/kg for human male subjects (claim 11).
Zygun et al. does not teach or suggest a method wherein the subject suffers from HH, a TBI associated impairment induced by an injury to the hypothalamus or pituitary gland, or impairment induced by suppression of synthesis and secretion of hormones produced by the hypothalamic-pituitary-gonadal (HPG) axis. Zygun et al. does not teach or suggest the specific sequences of claim 5, or sequences of 90% identity thereto, nor does it teach or suggest that the subjects are capable of normal adult gonadal hormone synthesis and secretion.
Barton et al. discloses that individuals suffering from TBI frequently develop HH [see p.2 paragraph 1] (claim 1), which is characterized by low testosterone levels [see p.2 Introduction] and/or low or inappropriately normal gonadotropin levels [see p.7 paragraph 4], demonstrating dysfunction of the HPG axis (claim 4). Further, Barton et al. explains that HH frequently results from damage to the pituitary gland [p. 8 paragraph 1] (claim 3).
It would have been obvious to combine the disclosure of Zygun et al. of administering hCG to subjects suffering from TBI with the teachings of Barton et al., to restore gonadal hormone function in individuals with a pituitary gland injury or impaired HCG axis following TBI because the art teaches that HH is a common consequence of TBI and results from damage to the pituitary and/or from an impaired HCG axis. Furthermore, there would be a reasonable expectation of success as one would reasonably believe that administering hCG to TBI patients with HH, which is also characterized by low gonadotrophin levels, would have the effect of stimulating the gonads to produce normal gonadal hormones, thereby inducing neurogenesis and improving cognitive outcomes.
Regarding claim 15, Zygun et al. does not limit administration to subjects exhibiting hypogonadism nor does it exclude subjects having normal circulating gonadal hormone levels. Thus, because Zygun et al. administers hCG broadly to TBI subjects without limitation, would reasonably assume that the subject population encompasses TBI subjects having normal gonadal hormone levels, and selecting this subset of subjects from the broader population would have been obvious without evidence that hormonally normal subjects would respond differently (claim 15).
Regarding claim 5, the sequences recited encode the native human alpha and beta subunits of hCG and hLH. hCG and hLH are well characterized proteins with subunit sequences that were publicly known at the time of the invention. More specifically, SEQ ID NO: 1 was available as of May, 2009 [see UniprotKB: C0KRQ8], SEQ ID NO: 2 as of July, 2015 [see UniprotKB: A0A0F7RQP8] and SEQ ID NO: 3 as of March 2002 [see UniprotKB: Q8WXL0]. It would have been obvious to use the native alpha and beta subunits in the modified method of Zygun et al. as it was routine in clinical and experimental practice to do so (claim 5).
Therefore, claims 1, 3-5, 7, 8, 11, 15, and 16 are rejected under 35 U.S.C. 103.
Claims 1, 6, 9, 12, 13, 17, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Zygun et al. in view of Barton et al., and in further view of Lee et al.
Claims 1, 6, 9, 12, 13, 17, and 18 are drawn to a method of treating TBI induced HH.
The disclosure of Zygun et al. and Barton et al. are discussed above.
The combination of Zygun et al. and Barton et al. fail to teach or suggest the administration lengths and frequencies of claims 6 and 9, the effective amounts of claims 12 and 13, or that the subjects are not capable of normal adult gonadal hormone synthesis and secretion or wherein the subject is further administered a gonadal hormone as required by claims 17 and 18.
Lee et al. discloses several hCG administration protocols, including administering hCG at a rate of two to three time per week [see p. 3 paragraph 1] (claim 6), and further teaches a regimen comprising administering testosterone replacement therapy (TRT) to hypogonadal men and periodically cycling TRT off and replacing it with 3000IU of hCG every other day for four weeks [see p. 2 paragraph 7] (claims 9, 12, 13, 17, and 18).
Regarding claims 12 and 13, the specification defines an “effective amount” to include dosages that yield acceptable therapeutic effects, and notes that dosages may be adjusted based on the interval of administration. Accordingly, Lee et al. administering 3,000IU hCG every other day for 4 weeks corresponds to an effective amount of about 42,000IU, or 466IU/KG for a 90kg human male, falling within the claimed range because the total effective exposure, in light of the specification’s interval guidance, achieves an effective amount.
Regarding claims 17 and 18, the specification defines subjects not capable of normal adult gonadal hormone synthesis and secretion as those having circulating gonadal hormone concentrations outside the normal adult reference ranges. Lee et al. expressly discloses administering testosterone and hCG to men with hypogonadism, which necessarily requires the subjects to have reduced gonadal hormone synthesis and secretion, thereby satisfying the limitations of claims 17 and 18 in light of the specification’s definition of “not capable.”
Although Lee et al. discloses these administration schedules and diagnostic steps in the context of reproductive health, the reference demonstrates that hCG was routinely administered according to repeated dosing schedules over multi-week treatment periods and that hCG could be paired with a gonadal hormone such as testosterone to hypogonadal subjects. As such, it would have been obvious to combine the modified method of Zygun et al. of administering hCG to subjects suffering from TBI induced HH, with the teachings of Lee et al. of administering hCG according to a known and routine administration timeline, to subjects suffering from TBI induced HH. Additionally, it would have been obvious to further administer a gonadal hormone, such as testosterone, to subjects not capable of normal adult gonadal hormone synthesis and secretion with a reasonable expectation that it would increase circulating gonadal hormone levels, as testosterone replacement therapy was a routine standard of care that the art teaches can be paired with hCG.
Therefore, claims 1, 6, 9, 12, 13, 17, and 18 are rejected under 35 U.S.C. 103.
Claims 1, 7, 8, 11-13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Zygun et al. in view of in view of Barton et al., and further in view of Gulekli et al.
Claims 1, 7, 8, 11-13, and 16 are drawn to a method of treating TBI induced HH.
The disclosure of Zygun et al. and Barton et al. are discussed above.
The combination of these references fails to teach or suggest the effective amounts of claims 12 and 13 in female subjects.
Gulekli et al. discloses administration of hCG to female patients at doses of 10,000 IU up to 20,000 IU to stimulate gonadal hormone production [see abstract]. Using an average adult female body weight of 77kg as discussed above, a 20,000 IU dose of hCG corresponds to approximately 260 IU/kg (claim 12) but slightly below the claimed range of 300-500 IU/kg. However, lighter subpopulations of women, such as Asian women with an average weight of 61kg [see CDC, p.7], would receive 328 IU/kg, which falls within the claimed range of 300-500 IU/kg (claim 13). Regardless, given that the specification defines “about” to be plus or minus 10%, in addition to the routine nature of dose optimization in the art, it would have been obvious to adjust the administration amounts to fall within the range of 300-500 IU/kg. Applying the known hCG treatment as taught by Gulekli et al. to the modified method of Zygun et al. would involve a predictable use of a known treatment for its known physiological effect, with a reasonable expectation of success.
Therefore, claims 1, 7, 8, 11-13, and 16 are rejected under 35 U.S.C. 103.
Claims 1 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Zygun in view of Barton et al. and Lee et al., and further in view of McCullers et al. (01/2002) and McCullers et al. (08/2002).
Claims 1 and 14 are drawn to a method of treating TBI induced HH.
The disclosure of Zygun et al., Barton et al., and Lee et al. are discussed above.
The combination of these references fails to teach or suggest the use of RU-486.
McCullers et al. (08/2002) discloses that TBI alters glucocorticoid receptor expression and regulation in the hippocampus [see p. 47, section 4.4]. McCullers et al. (01/2002) disclose that pretreatment with RU-486, a glucocorticoid receptor antagonist, protects hippocampal neurons following TBI [see Abstract], indicating that administration of RU-486 is known to mitigate glucocorticoid-mediated neural injury associated with TBI and could improve neurobehavioral outcomes (i.e., information processing, perceptual functioning, and memory) [see Conclusion].
It would have been obvious to further administer RU-486 to a subject suffering from TBI induced HH with a reasonable expectation that it would mitigate glucocorticoid-mediated hippocampal injury as a means of preserving the neurological pathways relevant to cognitive function. Furthermore, one would have been motivated to administer RU-486 in combination with hCG to address multiple hormonal pathways known to contribute to neurological injury following TBI. Such a combination represents predictable use of known agents for treating the same condition and does not require any synergistic effects.
Therefore, claims 1 and 14 are rejected under 35 U.S.C. 103.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over NIH Grant 1I21RX001371-01 in view of Barton et al., and further in view of Lopez-Rodriguez et al.
Claim 19 is drawn to a method of treating TBI in a subject that is capable of normal hormone synthesis.
The disclosure of 1I21RX001371-01 and Barton et al. are discussed above.
The combination of these references fails to teach or suggest a method of determining that the subject is capable of normal adult hormone synthesis and secretion.
Lopez-Rodriguez discloses that TBI alters circulating gonadal hormone levels and describes determining circulating hormone levels by collecting blood from a subject, extracting plasma, measuring testosterone [see p. 3985, Quantitative Analysis of Neuroactive Steroids”], and comparing the measured testosterone levels to a control sample to determine if levels fall below control ranges [see p. 3987, Figures A, B, and C]. These deficits are associated with poorer outcomes [see p. 3991, paragraph 3].
It would have been obvious to determine gonadal hormone status of a TBI subject before administering treatment as the art teaches that circulating levels of gonadal hormones are correlated with negative outcomes after TBI, and as such, a person having ordinary skill in the art would have been motivated to measure circulating gonadal hormones, as described by Lopez-Rodriguez, to evaluate endocrine dysregulation after TBI and thereby provide more appropriate therapeutic interventions.
Therefore, claim 19 is rejected under 35 U.S.C. 103.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Zygun in view of Barton et al. and Lee et al., and further in view of Carnegie.
Claim 20 is drawn to a method of treating TBI in a subject that is not capable of normal hormone synthesis.
The disclosure of Zygun et al., Barton et al., and Lee et al. are discussed above.
The combination of these references fail to teach or suggest a step comprising determining that the subject is not capable of normal adult gonadal hormone synthesis and secretion.
Carnegie teaches a method of diagnosing hypogonadism comprising measurement of serum testosterone, a sex steroid, in addition to prolactin, FSH, and LH levels, as compared to normal ranges [see p.54, right column, paragraph 2] (claim 20). It would have been obvious to a person of ordinary skill in the art seeking to treat TBI patients with hypogonadism to combine the teachings of Zygun and Lee et al. with the diagnostic method of Carnegie to identify individuals that are not capable of normal gonadal hormone synthesis and secretion and administer hCG and testosterone according to a known and routine administration timeline.
Therefore, claims 1 and 20 are rejected under 35 U.S.C. 103.
Response to arguments
35 U.S.C. 112
Applicant argues that the rejection of claims 10, 16, and 20 under 35 U.S.C. 112(b) as being indefinite has been overcome in view of the amendments to those claims.
This argument is found persuasive for claims 10 and 20 but not for claim 16. Claim 16 still recites the phrase “optionally” and, as stated above, the phrase reads as an exemplary term. Description of examples or preferences is properly set forth in the specification rather than the claims.
Therefore, the rejection of claims 10 and 20 under 35 U.S.C. 112(b) is withdrawn but the rejection of claim 16 under 35 U.S.C. 112(b) is maintained.
1I21RX001371-01
Applicant argues that 1I21RX001371-01 is deficient in that it does not teach or suggest administration of an effective amount of hCG, hLH, or a combination thereof, to subjects with TBI induced HH as required by the presently amended claim 1. Applicant argues that 1I21RX001371-01 is only prospective and does not teach that TBI targets a particular part of the brain.
In view of the amended claim 1, these arguments are found persuasive. However, it is noted that conclusive proof of efficacy is not required, and that the relevant inquiry under 35 U.S.C. 103 is whether the prior art would have provided a person having ordinary skill in the art with a reasonable expectation of success in carrying out the claimed method [see MPEP 2143.02]. In this sense, the grant does not merely propose testing hCG in a TBI model, but also teaches that TBI suppresses circulating gonadotrophin and sex steroid concentrations and describes a resulting neurosteroid deficient state. 1I21RX001371-01 teaches that hCG promotes neurogenesis and expressly proposes hCG treatment following TBI to enhance neurogenesis and cognitive recovery. This teaching is pertinent to the discussions below.
Therefore, the rejections of claims 1 and 10 under 35 U.S.C. 102 and claims 1, 5, 10, and 15 under 35 U.S.C. 103 are withdrawn.
1I21RX001371-01 in view of Barton et al.
Applicant argues that neither reference suggests treating HH subgroup with hCG or hLH, and neither establishes that doing so would induce cognitive recovery. As such, Applicant argues that there was neither a motivation to make the proposed combination nor a reasonable expectation of success, and that arriving at the claimed method requires hindsight. Applicant notes that Barton specifically excludes individuals with a history of hLH treatment, which suggests that applicant is arguing teaching away.
Applicant’s arguments have been fully considered but they are not persuasive.
First, the rejection does not rely upon 1I21RX001371-01 as teaching HH or on Barton et al. as teaching administration of hCG or hLH, rather, 1I21RX001371-01 and Barton et al. are relied upon for their own respective teachings. That is, 1I21RX001371-01 teaches that hCG and hLH are hormones that are reduced during TBI but promote neurogenesis, and expressly proposes hCG treatment following TBI to enhance neurogenesis and cognitive recovery. Barton et al. teaches that persistent HH is a common consequence of TBI, thereby identifying the endocrine impairment that 1I21RX001371-01 teaches is an outcome of TBI. A person having ordinary skill in the art seeking to use the method of 1I21RX001371-01 would therefore have had a reason to apply that treatment to TBI subjects exhibiting HH as described by Barton. Accordingly, applicant’s argument that Barton et al. does not teach administration of hCG or hLH does not render the claimed method nonobvious over the prior art.
Applicant’s argument that Barton et al. does not teach or suggest that administration would induce cognitive recovery is similarly not persuasive because 1I21RX001371-01 provides the teachings regarding the use of hCG to promote neurogenesis and induce cognitive recovery.
Applicant’s argument that Barton et al. excludes patients with a history of hLH therapy is not persuasive because it only describes the patient population selected for that study that best reduces confounding variables. This does not discredit or discourage the use of hCG in patients with TBI induced HH as rendered obvious by the combination of 1I21RX001371-01 and Barton et al.
Applicant’s assertion that the only suggestion to administer hCG and/or hLH to TBI subjects with HH comes from Applicant’s disclosure or hindsight reasoning is unpersuasive for the reasons discussed above.
Applicant’s argument that there is no reasonable expectation of success is not persuasive as 1I21RX001371-01 provides specific biological rationale for administration of hCG following TBI, while Barton et al. teaches that TBI patients often exhibit deficient gonadotrophin signaling and HH. In view of these teachings, one would have reasonably expected that administration of hCG to a TBI patient with HH to induce neurogenesis and cognitive recovery as taught by 1I21RX001371-01.
Therefore, the rejection of claims 1, 3-5, 10, and 15 under 35 U.S.C. 103 is maintained.
1I21RX001371-01 in view of Lopez-Rodrigues et al.
Applicant argues that Lopez-Rodrigues et al. fails to cure the deficiencies of 1I21RX001371-01 as it does not disclose administering hCG, hLH, or a combination thereof to a subject suffering from TBI induced HH.
This argument is not found persuasive because, at the outset, claim 19 does not require the subject suffer from TBI and HH, only that the subject suffer from TBI. Furthermore, 1I21RX001371-01 provides the teachings concerning administration of hCG following TBI as discussed above while Lopez-Rodriguez et al. is relied upon for the additional determination of gonadal hormone status. In view of the teaching that TBI can alter the levels of circulating hormone levels, one would have been motivated to evaluate the gonadal hormone status of a TBI subject to determine an appropriate therapeutic approach.
Therefore, the rejection of claim 19 under 35 U.S.C. 103 is maintained.
Zygun et al.
Applicant argues that Zygun et al. is deficient in that it does not teach or suggest administration of an effective amount of hCG, hLH, or a combination thereof, to subjects with TBI induced HH as required by the presently amended claim 1.
Applicant’s argument is directed to a limitation that was newly added to claim 1, thereby requiring a modification as necessitated by amendment. The rejection above of Zygun et al. in view of Barton et al. cures this deficiency. More specifically, Zygun et al. teaches administration of hCG to subjects following TBI, while Barton et al. teaches that HH is a frequent consequence of TBI. Thus, the absence of an express teaching of HH diagnosis in Zygun et al. does not render the claimed method nonobvious over the references.
Therefore, the rejections of claims 1, 7, 8, 11, and 16 under 35 U.S.C. 103 are maintained.
Zygun et al. in view of Lee et al.
Applicant argues that Zygun et al. and Lee et al. are deficient in that they do not teach or suggest administration of an effective amount of hCG, hLH, or a combination thereof, to subjects with TBI induced HH as required by the presently amended claim 1.
As discussed above, applicant’s argument is directed to a limitation that was newly added to claim 1, thereby requiring a modification as necessitated by amendment. The rejection above of Zygun et al. in view of Barton et al. and Lee et al. cures this deficiency. In addition to Zygun et al. and Barton et al. as discussed above, Lee is relied upon for its additional administration schedules, dosages, and treatment of hypogonadal subjects. Thus, the absence of an express teaching of TBI diagnosis in Lee et al. does not render the claimed method nonobvious over the references.
Therefore, the rejection of claims 1, 6-9, 11-13, and 16-18 under 35 U.S.C. 103 is maintained.
Zygun et al. in view of Lee et al., McCullers I, and McCullers II
Applicant argues that the combination of these references is deficient in that it they do not teach or suggest administration of an effective amount of hCG, hLH, or a combination thereof, to subjects with TBI induced HH as required by the presently amended claim 1.
As discussed above, applicant’s argument is directed to a limitation that was newly added to claim 1, thereby requiring a modification as necessitated by amendment. The rejection above of Zygun et al. in view of Barton et al., Lee et al., McCullers I, and McCullers II cures this deficiency. In addition to Zygun et al., Barton et al., and Lee et al. as discussed above, McCullers I and McCullers II are relied upon for only for the additional use of RU-486 in the treatment of TBI. Thus, the absence of an express teaching of administration of gonadal hormones or treatment of HH by McCullers I and II does not render the claimed method nonobvious over the references.
Therefore, the rejection of claim 14 under 35 U.S.C. 103 is maintained.
Zygun et al. in view of Lee et al. and Carnegie et al.
Applicant argues that the combination of these references is deficient in that it they do not teach or suggest administration of an effective amount of hCG, hLH, or a combination thereof, to subjects with TBI induced HH as required by the presently amended claim 1.
As discussed above, applicant’s argument is directed to a limitation that was newly added to claim 1, thereby requiring a modification as necessitated by amendment. The rejection above of Zygun et al. in view of Barton et al., Lee et al., and Carnegie et al. cures this deficiency. In addition to Zygun et al., Barton et al., and Lee et al. as discussed above, Carnegie et al. is relied upon for only for diagnostic assessment of HH. Thus, the absence of an express teaching of administration of gonadal hormones or treatment of HH by Carnegie et al. does not render the claimed method nonobvious over the references.
Therefore, the rejection of claim 20 under 35 U.S.C. 103 is maintained.
Zygun et al. in view of Gulekli et al.
Applicant argues that the combination of these references is deficient in that it they do not teach or suggest administration of an effective amount of hCG, hLH, or a combination thereof, to subjects with TBI induced HH as required by the presently amended claim 1.
As discussed above, applicant’s argument is directed to a limitation that was newly added to claim 1, thereby requiring a modification as necessitated by amendment. The rejection above of Zygun et al. in view of Barton et al., and Gulekli et al. cures this deficiency. In addition to Zygun et al., Barton et al., as discussed above, Gulekli et al. is relied upon for only for the additional administration dosages for stimulating gonadal hormone production. Thus, the absence of an express teaching of treatment of HH by Gulekli et al. does not render the claimed method nonobvious over the references.
Therefore, the rejection of claims 1, 7, 8, 11-13, and 16 under 35 U.S.C. 103 is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TIRONE D. JOHNSON/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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