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 .
DETAILED ACTION
Claim Status
Claims 1-4, 6-10 and 12 are pending. Claims 1-4, 6-7, 9 and 12 are being examined in this application. In the response to the restriction requirement, Applicants elected lactoferrin, grape seed extract, other natural antimicrobial peptides not comprised, herpes virus, and medical device. Claims 8 and 10 are withdrawn as being drawn to a nonelected species.
Response to Amendment
The declaration under 37 CFR 1.132 filed on 3/16/2026 is insufficient to overcome the rejection of claims 1-4, 6-7, 9 and 12 based upon 35 U.S.C. 112(a) and 35 U.S.C. 103 as set forth in the last Office action because:
Applicant argues that “[t]he anti-viral effects discussed above are not specific to a particular virus type. Virtually all viruses, whether DNA or RNA, enveloped or non-enveloped, initially interact with the target cell through negatively charged moieties located on the cell surface, such as heparan sulfate proteoglycans, sialic acids, gangliosides, or negatively charged receptors (e.g., CXCL4)”.
Applicant also argues that “[t]he oxidative destabilization of surface proteins affects motifs that are structurally conserved among different viruses, including disulfide bonds, aromatic clusters, and hydrophobic domains. Thus, it is respectfully submitted that, for all of the reasons discussed above, the skilled person would not be forced to undergo undue experimentation to make and use the invention as claimed in order to treat each and every viral infection”.
Applicant further argues that “[t]he synergistic, anti-viral activity shown by the composition tested in Example 9 of the present application, comprising lactoferricin and grape seed extract (GSE), is based on a dual, orthogonal interference of the active ingredients and of the plant extracts with the virus' ability to infect cells. In particular: the strong cationic and amphipathic nature of the active ingredient (lactoferricin peptide in Example 9) operates the electrostatic neutralization of the virus and/or masks the anionic moieties on the target cell's surface; this prevents the attraction of the virus to the target cell, the engagement of its receptors, and the eventual fusion of the virus-cell membranes. The polyphenolic components of the plant extract (GSE in Example 9) exhibit an oxidative and conformational destabilization of the proteins of the virus surface, reduces the flexibility and fusogenicity of the viral proteins, essential for membrane fusion or capsid uncoating. As a matter of fact, all the active ingredient's peptides and the polyphenolic components of the plant extract presently claimed share the same physical-chemical features that are behind the synergic anti-viral effects of the combination tested in Example 9. Therefore, the synergy exhibited by lactoferricin and GSE is also present in the other combinations of active ingredients and plant extract(s), as presently claimed. Moreover, as also discussed above, the synergistic anti-viral effects is not specific to a particular virus type. Consequently, the method of the invention, comprising administration of a synergistic composition for the treatment of viral infection is not obvious over the combinations of the cited references”.
Applicant’s arguments have been fully considered but they are not persuasive.
As discussed in the rejection below, viral infections such as ebola are untreatable. The Examiner further submit the reference of CDC (Marburg Virus Disease, September 24, 2025), which clearly teaches that Marburg, just like ebola, is untreatable (page 3, “Treatment and recovery”).
Therefore, without a working example, and given the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to make and use the invention as claimed.
With respect to Applicant’s arguments regarding synergy, Example 9 of the instant application shows that the FIC Index is 0.75, which, in contrary to Applicant’s arguments does NOT show synergy, but rather indifference or additive effect.
The Examiner submits the reference of Emery Pharma (downloaded from URL:< https://emerypharma.com/solutions/cell-microbiology-services/antimicrobial-synergy-study-checkerboard-testing/>), which clearly teaches that FIC Index of 0.5-4 shows indifference or additive effect (see page 1).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
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.
This rejection is maintained.
Claims 1-4, 6-7, 9 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of herpes, influenza A virus, and SARS-COV-2, does not reasonably provide enablement for the treatment of each and every viral infection. 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.
The MPEP states:
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.”
(A) The breadth of the claims; and (B) The nature of the invention;
The instant invention pertains to a method of treating viral infections, the method comprising the step of administering to a subject in need thereof an effective amount of a composition comprising: i) 0.0005 wt% to 20 wt% of an active ingredient comprising lactoferrin or at least one peptide comprising lactoferricin, polylysine, natamycin or a mixture thereof, or a mixture of lactoferrin and said at least one peptide, and ii) 0.001 wt% to 10 wt% of at least one plant extract comprising antioxidants selected from catechins, polyphenols and their mixtures, said plant extract being grape seed extract, elderberry extract, green tea extract, grapefruit seed extract or a mixture thereof.
(C) The state of the prior art;
Generally, the state of the art with respect to the treatment of viral infections teach that ebola is untreatable (see CIDRAP News, 2003, page 1, line 2). Similarly, Mullin (Fierce Biotech, 2014) teaches that ebola cannot be treated (page 1, lines 1-2).
Thus, a method of treatment of each and every viral infection as claimed is uncertain.
(D) The level of one of ordinary skill;
The skill of those skilled in the art is high.
(E) The level of predictability in the art;
The skilled artisan would view that the treatment of viral infections is highly unpredictable.
(F) The amount of direction provided by the inventor; and (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The specification provides experimental results which illustrate that herpes, influenza A virus, and SARS-COV-2 can be treated with the claimed composition. However, the specification fails to provide scientific data and working embodiments with respect to showing the treatment of each and every viral infection. Note that lack of a working example, is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP 2164.
The MPEP (2164.02) states that " The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970).” The MPEP further states that
PNG
media_image1.png
18
19
media_image1.png
Greyscale
“Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.”
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to make and use the invention as claimed.
Response to Arguments
Applicant’s arguments filed on 3/16/2026 have been fully considered but they are not persuasive.
Applicant’s arguments have been discussed above under “Response to Amendment”.
For the reasons stated above the rejection is maintained.
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.
This rejection is maintained.
Claims 1-4, 6-7 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Rapacioli et al. (WO 2019/021175) in view of Pasqua et al. (Chapter 10. Antimicrobial and antiviral activities of grape seed extracts; January 1, 2016).
With respect to claims 1-4 and 6, Rapacioli et al. teach a composition comprising lactoferrin for the treatment of infections caused by pathogenic agents such as a virus (abstract; page 5, lines 8-15; claim 7).
Rapacioli et al. also teach that the composition comprises 0.01 wt% to 1 wt% of lactoferricin (claim 5).
Rapacioli et al. do not teach that the composition further comprises at least one plant extract.
Pasqua et al. teach that grape seed extract (GSE) has antimicrobial and antiviral activities (abstract; page 217, 2nd-4th paras).
Pasqua et al. also teach that “[A]ntimicrobial activity together with lack of toxicity suggests that GSE could he used for the prevention and control of infection diseases without side effects, making greater potential for grape in the field of food and pharmaceutical application’ (para bridging pages 211-212).
The MPEP 2144.06 states that "It 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 them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that lactoferrin and GSE are effective in treating viral infections, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating viral infections. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed concentration of plant extract (i.e. GSE) and weight ratio, the MPEP 2144.05 A states that “[G]enerally, 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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum concentration of GSE, and weight ratio, by normal optimization procedures known in the pharmaceutical art.
With respect to claim 7, Rapacioli et al. teach that lactoferricin is obtained by enzymatic hydrolysis of lactoferrin, preferably through an immobilized enzyme (claim 6).
With respect to claim 12, Rapacioli et al. teach that the composition is in the form of a food (page 2, lines 8-9; page 7, lines 7-8).
Response to Arguments
Applicant’s arguments filed on 3/16/2026 have been fully considered but they are not persuasive.
Applicant’s arguments have been discussed above under “Response to Amendment”.
For the reasons stated above the rejection is maintained.
This rejection is maintained.
Claims 1-4, 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Jenssen et al. (Cell Mol Life Sci. 2005 Nov 2;62(24):3002-3013) in view of Su et al. (Appl Environ Microbiol. 2011 Jun;77(12):3982-7).
With respect to claims 1-4, 6 and 9, Jenssen et al. teach that lactoferrin has anti-HSV (herpes simplex virus) activity (abstract; passim).
Jenssen et al. do not teach that the composition further comprises at least one plant extract.
Su et al. teach that “[T]hough the antibacterial effects of grape seed extract (GSE) have been well studied, there is very little documentation on its antiviral effects……...Resveratrol (RV) is a nonflavonoid polyphenol that is present in both seed and skin of grapes, being produced in response to physiological stimuli and environmental stress. It has been shown that RV is effective against a wide variety of viruses. RV is reported to strongly inhibit the in vitro and in vivo replication of influenza virus and also has strong antiviral activity against herpes simplex virus type 1” (page 3985, left column, 2nd para).
The MPEP 2144.06 states that "It 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 them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that lactoferrin and GSE are effective in treating herpes simplex virus infections, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating herpes simplex virus infections. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to the claimed concentration of lactoferrin, plant extract (i.e. GSE) and weight ratio, the MPEP 2144.05 A states that “[G]enerally, 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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum concentration of lactoferrin, GSE, and weight ratio, by normal optimization procedures known in the pharmaceutical art.
Response to Arguments
Applicant’s arguments filed on 3/16/2026 have been fully considered but they are not persuasive.
Applicant’s arguments have been discussed above under “Response to Amendment”.
For the reasons stated above the rejection is maintained.
This rejection is maintained.
Claims 1-4, 6-7, 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Jenssen et al. (Cell Mol Life Sci. 2005 Nov 2;62(24):3002–3013) in view of Su et al. (Appl Environ Microbiol. 2011 Jun;77(12):3982-7) as applied to claims 1-4, 6 and 9 above, and further in view of Rapacioli et al. (WO 2019/021175).
The teachings of Jenssen et al. and Su et al. with respect to claims 1-4, 6 and 9 have been discussed above.
Jenssen et al. and Su et al. do not teach that lactoferrin is obtained by enzymatic hydrolysis, or that the composition is in the form of a food.
Rapacioli et al. teach a composition comprising lactoferrin for the treatment of infections caused by pathogenic agents such as a virus (abstract; page 5, lines 8-15; claim 7).
Rapacioli et al. also teach that lactoferricin is obtained by enzymatic hydrolysis of lactoferrin, preferably through an immobilized enzyme (claim 6).
Rapacioli et al. further teach that the composition is in the form of a food (page 2, lines 8-9; page 7, lines 7-8).
It would have been obvious to one of ordinary skill in the art to obtain lactoferrin by enzymatic hydrolysis because Rapacioli et al. teach that lactoferrin, when used for the treatment of infections, is obtained by enzymatic hydrolysis.
Furthermore, the skilled artisan would have been motivated, with a reasonable expectation of success, to make the composition in the form of a food because Rapacioli et al. teach that a composition comprising lactoferrin, for the treatment of infections, is in the form of a food.
Response to Arguments
Applicant’s arguments filed on 3/16/2026 have been fully considered but they are not persuasive.
Applicant’s arguments have been discussed above under “Response to Amendment”.
For the reasons stated above the rejection is maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MELISSA FISHER can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658