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 .
Status of Claims
Claims 1, 3, 6, 7, 8, 9, 11, 14, 15, 21, 25, 26, 29 and 57-62 are pending and under examination.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 9-30-2025 is acknowledged.
Information Disclosure Statement
The information disclosure statement has been considered. An initalled copy is enclosed.
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 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.
Claims 1, 3, 6, 7, 8, 9, 11, 14, 15, 21, 25, 26, 29 and 57-62 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.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
While all of the factors have been considered, only those deemed necessary to establish a prima facie case are set forth below.
Scope or breadth of the claims and Knowledge of the prior art
The claims are directed to treatment of a “frailty condition” by administering an effective amount of a gelsolin molecule to treat the frailty condition. The use of the term “frailty condition” is not defined in the medical arts. The specification defines “frailty condition” as “a physical condition in a subject” (specification page 6, line 29). The frailty condition is not limited to an age-related frailty condition and can be associated with one or more of: physical trauma, physical confinement, hospitalization, chronic physical inactivity, limited mobility, diabetes, a disease condition, paralysis and a chronic disease condition (see specification page 3, lines 31-34). This definition includes a vast array of physical conditions that the gelsolin molecule is said to be effective for treating. Peddada et al teach that numerous diseases are associated with decrease levels of gelsolin (see Peddada et al, Medical Hypothesis, 78:203-210, 2012; of record) at page 204, column 2, first paragraph and page 205, Table 1, as compared to non-diseased individuals. However, gelsolin levels do not statistically predict mortality and does not distinguish between survivors and non-survivors (page 205, column 2, Figure 1A and B. Other than being a general health marker, gelsolin supplementation has not been demonstrated to provide treatment of these other “frailty conditions” which naturally have the claimed characteristics and symptoms. The specification fails to teach any benefit to gelsolin administration in patients with characteristics and symptoms as claimed or any benefit to provide physical activity in general. While plasma gelsolin may be a general prognostic marker of health, it does not follow that supplementation provides for treatment of frailty conditions having the characteristics and symptoms claimed. Even as late as 2018, plasma gelsolin remains a therapeutic target and its interactions in disease are complex. Feldt et al (Expert Reviews in Molecular Medicine, 20:e7:1-10, 2019; of record) teach that gelsolin is only a potential treatment for a variety of diseases having the claimed characteristics and symptoms and has been tested in very few (see page 8, column 1, GSN as a therapeutic target). Feldt et al teach that gelsolin has the potential to become a useful therapeutic, however, further research is required. The ability to treat characteristics and symptoms as claimed in the absence of a decrease in gelsolin is unclear and untaught by the specification.
Guidance provided by inventor/working examples
The specification teaches that when gelsolin molecule is administered to a subject on an ongoing, regular basis wherein the subject has a diagnosis of phenotypic frailty or prefrailty and the subject has two or more of physical weakness, exhaustion or physical inactivity then the administration shows reduced frailty or prefrailty in these characteristics (see Examples 2-6). The specification does not teach treating the vast majority of frailty conditions as broadly defined in the specification or the symptoms as claimed (claims 14 and 15). Exhaustion/fatigue and other claimed characteristics and symptoms are characteristics and symptoms of multiple physical conditions as defined in the specification. The specification does not teach effective treatment of physical condition of diseases having one or more of the characteristics as recited in the claims such that the one or more of the characteristics are improved or impairment reduced where plasma gelsolin is known to be reduced. The specification also does not teach the effective amelioration or treatment of symptoms set forth in claims 14 to 15. Therapeutic application or benefit of gelsolin replacement has not been demonstrated in these physical conditions. Lee et al (Annals of Surgery 243(3):399-403, 2006) teach that plasma gelsolin levels are critical indicators in mortality in critically ill surgical (open-chest or abdominal) or trauma (trauma or burns) patients. These hospitalized patients necessarily comprise a physical condition that has the characteristics of exhaustion, weakness and physical inactivity and have not been demonstrated to have the requisite response to gelsolin therapy. The specification does not teach any therapeutic benefit for the vast majority of physical conditions contemplated within the scope of “frailty condition” as set forth in the claims. The specification does not teach that exhaustion, weakness or physical inactivity can be treated as claimed as a result of any frailty condition that is not defined by the art as frailty or pre-frailty. The specification does not teach that symptoms such as muscle wasting, cachexia, physical injury, impaired locomotion or decreased physical stability can be effectively treated in any subject no standard means of measuring the status has been presented. . The symptoms have numerous associations with different diseases and where the plasma gelsolin has not been investigated and as such, the supplementation of gelsolin would have an unpredictable outcome. A representative number of physical conditions associated with exhaustion/fatigue such as adrenal insufficiency, infections, autoimmune disorders, anemia, fibromyalgia, chronic kidney disease, cancer, stress have not been demonstrated by the specification to be effectively treated by means of reducing/decreasing/ameliorating a characteristic or symptom as claimed herein.
Level or degree of predictability
The treatment of conditions of mammalian subjects is highly unpredictable. Here the teachings of the specification are for improvement in limited characteristics in a particular patient having been diagnosed with a particular syndrome (frailty or pre-frailty). This cannot be extended to encompass treatment of diseases having as a characteristic or symptom of frailty in common, without more. No single therapeutic has been demonstrated to treat the claimed characteristics and/or symptoms. There is no teaching of the specification that provides evidence to support efficacy in a number of characteristics or symptoms as claimed. However, in applications directed to inventions in arts but where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991).
Quantity of experimentation
The quantity of experimentation would be extensive to assess the different characteristics and symptoms in a variety of diseases administer gelsolin and then determine efficacy without a reasonable expectation of success.
In light of the foregoing factors, the evidence as a whole suggests that the specification, in light of the level of knowledge in the art, does not enable one of ordinary skill to make or use the invention over the full scope of the instant claims without undue experimentation. Consequently, the claims are prima facie non-enabled.
Claims 9, 11, 14 and 15 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The claim 9, recites that the determined status is compared to a control status, what is the control status ? A control status is not defined in the specification and as such the determined status is compared to an unknown and per se indefinite
The claim 11 recites that the subjects liklihood of survival is compared to a control likelihood of survival, what is the control ? A control liklihood is not defined in the specification and as such the subject’s liklihood is compared to an unknown control liklihood and per se indefinite.
As to claims 14 and 15, the claims states “decreased physical stability”, however the phrase in indefinite because it is unclear what the comparison is to. Decreased from what ?
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) 1, 3, 6, 7, 8, 9, 11, 14, 15, 21, 25, 26 and 57-62 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al (The Journal of Infectious Diseases, 220:1498-1502, published online July 9, 2019; of record).
Yang et al teach administration of plasma gelsolin improves survival in a murine model (i.e. subject is a mammal, claim 62) of pneumococcal pneumonia. Yang et al teach that the administration post infection provided for increased survival reduced morbidity and reduced weight loss (see page 1500, Figure 2(A-C)). The status of each of survival, weight loss and morbidity score were assessed at multiple time points, starting on day 1 after pneumonococcal infection. Yang et al teach that morbidity score was assessed using a composite index providing for symptoms of hunched, ruffled fur, partially closed eyes, prolapsed penis or splayed hind quarter and listlessness. The morbidity score reflected a cumulative score for exhaustion, weakness, impaired locomotion, decreased physical stability (see claims 1, 3, 6, 7, 8, 9, 11, 14, 15, 21, 25, 26 and 57-62). Weight loss (e.g. cachexia; age related frailty condition) was monitored daily before and after gelsolin administration. The status was assessed starting at day 0 and daily thereafter. Infection was begun on day 1 and treatment with recombinant human plasma gelsolin was give intraperitoneally on days 2 and 3 after infection (see page 1499, Figure 1 legend). Treatment with the gelsolin provides for decreased cachexia and decreased morbidity (e.g. claimed characteristics of frailty) and increased survival as compared to vehicle controls (see Figure 1, page 1500).
Claim(s) 1, 11, 14, 15, 21, 25, 26 and 57-62 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al (OFID, 2017:4 (Suppl 1) Abstract 1519, Session 167).
Yang et al teach administration of plasma gelsolin improves survival in a murine model (i.e. subject is a mammal, claim 62) of pneumococcal pneumonia. Yang et al teach that the administration post infection provided for increased survival and reduced weight loss (see abstract, “Results” and Graphs). The status of survival as copared to vehicle controls were assessed at multiple time points, daily, starting on day 1 after pneumonococcal infection on day zero and monitored for 10 days (i.e. determining staus of subject and controls at multiple time points, including before and after administering gelsolin). Yang et al teach that in each of three separate trials adminstration of multiple doses of recombinant human plasma gelsolin reduced weight loss (i.e. cachexia; age related frailty condition) and mortality. Increasing the dose of gelsolin increased the survival rate. Treatment with the gelsolin provides for decreased cachexia (weight loss) and increased survival as compared to vehicle controls. As such, Yang et al anticipates the claimed invention.
Conclusion
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/Patricia Duffy/Primary Examiner, Art Unit 1645