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
Applicant’s submission of Pre-appeal brief conference request filed on 03/03/2026 is duly acknowledged.
Pre-appeal Brief Conference Request Decision - Finality Withdrawn
Applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and therefore, the finality of that action is withdrawn as per decision letter sent by the office on 03/26/2026.
Claims 4, 9, 13 and 20 were previously canceled by the applicant.
Claims 1-3, 5-8, 10-12, 14-19 and 21-23 (elected invention of Group I, without traverse; drawn to “A method…to produce eye drops”), as currently amended, have been examined on their merits in this action, hereinafter.
Priority
This application claims benefit from a US provisional 62/967572 (filed on 01/29/2020), and is a CIP of PCT/US2019/030228 (filed on 05/01/2019), which claims priority form US provisional applications 62/733918 (filed on 09/20/2018) and 62/664939 (filed on 05/01/2018).
Claim Rejections - 35 USC § 103- Withdrawn
The rejections of claims 1-3, 5-8, 10-12, 14-19 and 21-23 under 103(a) as previously made by the examiner over Chiang et al (2009) taken with Abuhanoglu et al (2014), [Park et al (2017), as evidenced by Isman et al (2007)], Zyl et al (2011) and Friedman (WIPO 2018); and further in view of Semeraro et al (2014), have been withdrawn.
The following contains new grounds of objections/rejections of pending claims as presented by applicants on 08/04/2025 for applicant’s due considerations and perusal.
Claim Terms
It is noted that terms “additive” and “active components” have not been specifically defined by the applicants on record in the instant disclosure (see specification, page 3, [0016]; page 7 [0032]; page 11 [0043]-[0044], for instances).
Claim Rejections - 35 USC § 112 – New Grounds
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.
1. Claims 1-3, 5-8, 10-12, 14-19 and 21-23 (as amended) 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.
A. Claim 1, as currently amended, is reproduced herein below:
“1. (Currently Amended) A method, comprising:
collecting whole blood from a plurality of donors;
separating the whole blood to obtain a serum;
pooling the serum from a plurality of donors to form a pool of serum;
after pooling the serum, applying radiation to the pool of serum for viral inactivation; and
after applying radiation to the pool of serum, adding one or more additives to the serum to produce eye drops having supplemented concentrations of active components of the serum
The claim 1, as amended is directed to a method (for producing eye drops) that recites the limitations “adding one or more additives to the serum to produce eye drops having supplemented concentrations of active components of the serum”, wherein it is unclear as to what exactly is being done in said step of “adding one or more additives”. First, the claimed process does not provide any basis for “active components of the serum” per se that have been “supplemented” a given concentration (it is noted that the term “active component” has not been specifically defined by applicants on record; see instant disclosure, SPEC, [0032], [0038], [0040]; for instance). Second, it is not clear as to which active method step provides for such “supplementation” of “active components” in the serum, pooled, or otherwise after radiation. Also, it unclear if “adding one or more additives” is being taken as supplementing “active components of the serum”, or some other “active components” are being “supplemented” at certain “concentrations” in the serum, the specific step of which appears to be lacking in instant claim 1, as amended. The guidance in the disclosure of record does not appear to provide for such “supplemented concentrations of active components of the serum” after applying radiation to the pool of serum. Thus, the metes and bounds of the claimed process does not appear to be properly defined.
Since, none of the dependent claims (claims 2, 3, 5-8, 10-12, 14-19 and 21-23) as presented clarify all the points discussed above, they are also rejected as being indefinite for the same reasons of record. Appropriate correction is required.
B. Claim 6 recites the limitations “testing the whole blood collected from each donor for particular viruses”, without specifying what exactly are the “particulars” for the viruses required to meet the claimed limitations. The disclosure of record (see SPEC, p. 3, [0013]) does not provide guidance as to the specific requirements for such “particular viruses” in the donated whole blood samples per se. It is unclear as to what exactly is encompassed in scope of the claimed process by the aforementioned limitations. Thus, the metes and bounds of the claimed process does not appear to be properly defined. Appropriate correction is required.
NOTE: 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 (i.e., changing from AIA to pre-AIA ) 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.
Claim Rejections - 35 USC § 103- New Grounds
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.
1. Claims 1-3, 5-8, 11, 12, 14-16, 19, 21 and 22 (as currently amended) are rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al (2009; previously cited by examiner) taken with Nakamura et al (2003; NPL cited as ref. [U] on PTO 892 form), Versteegen et al (2016; NPL cited as ref. [V] on PTO 892 form), and [Park et al (2017; previously cited by examiner), as evidenced by Isman et al (2007, previously cited as pertinent prior art)].
Claim 1, as amended, is reproduced herein below:
“1. (Currently Amended) A method, comprising:
collecting whole blood from a plurality of donors;
separating the whole blood to obtain a serum;
pooling the serum from a plurality of donors to form a pool of serum;
after pooling the serum, applying radiation to the pool of serum for viral inactivation; and
after applying radiation to the pool of serum, adding one or more additives to the serum to produce eye drops having supplemented concentrations of active components of the serum
See also limitations of dependent claims 2, 3, 5-8, 11, 12, 14-16, 19, 21 and 22, as currently amended.
NOTE: The method as claimed has been interpreted as a method of making or producing eye drops; it is also noted that claimed scope encompasses production of eye drops from both, autologous as well as allogeneic donor blood serum, however instant claim 1 does not specify the “donor” population per se. Claim 1 also does not specify the type, amount or dose levels of radiation used for “viral inactivation” per se. It is also noted that instant disclosure does not specifically defined and/or disclosed as to what exactly is encompassed by the term “active component” and therefore the method step of “adding one or more additives” to the “pooled serum” has been taken as addition of an “additive” that helps in physical/chemical stabilization and/or preserving functional activity of the serum-based eye drops (and/or supplements component(s) naturally present in serum) produced by the method, as intended by the disclosure of record (see instant specification, page 3, [0016]-[0019]; page 7, [0032]; page 11, [0043]-[0044]).
Chiang et al (2009), while evaluating safety and efficacy of allogeneic serum in the treatment of persistent corneal epithelial defect (PED; see Abstract and Introduction) in patients for whom serum treatment is indicated but autologous serum is unavailable or unsuitable for use, disclose the method of making eye drops comprising collecting blood (20 or 40 ml peripheral blood) aseptically from one or more allogeneic donors (from the patient’s relatives; see entire section “Materials and methods” on page 291); wherein the allogeneic serum was prepared by using sterile technique and by centrifuging the blood at 1500 rpm (239 x g) at 4 degree C (i.e. low temperature processing to avoid degradation of whole blood components, etc.) for 10 minutes; wherein the clarified serum (i.e. devoid of blood cells) was aliquoted into 2 or 4, 5 ml plastic bottles and stored at 4 degree C. They also disclose that allogeneic serum eye drops were found to be safe and effective in treating PED, and thus offers a treatment alternative to autologous serum eye drops, which are normally used for dry eye related disorders (see section “Discussion” on page 291). Chiang et al disclose that the serum was first tested/screened using standard tests in blood bank screening (which includes blood serotyping and screening of infectious agents) to check for blood-borne diseases, human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus (see section “Materials and methods” on page 291).
However, the method comprising: 1) pooling the serum from a plurality of donors (see instant claim 1); 2) a step of applying radiation to the serum for viral inactivation; and 3) adding one or more additives to the serum to produce eye drops having supplemented concentrations of “active components” of the serum, has not been explicitly disclosed by Chiang et al, as discussed above.
Nakamura et al (2003), while studying the effects of D-beta-hydroxybutyrate (BHA) on corneal epithelia, disclose preparation of ophthalmic solutions for treating dry eye conditions (see Title, Summary on page 4682), wherein they employ pooled serum as ophthalmic preparation, collected in a sterile manner from six rats (see page 4683, section “Ophthalmic Solutions”), which was kept at 4 degree C and shielded from light until use, wherein 5%, 20%, and 100% of serum (v/v) were formulated in phosphate-buffered saline (PBS) and osmolarities adjusted with sodium chloride (NaCl) from 290 to 300 mOsm; and wherein the serum-based eye drops prepared from pooled serum were found to be effective in significantly suppressing chromatin condensation and apoptosis of treated epithelial cells (see Summary on page 4682).
Versteegen et al (2016), while reviewing the use of gamma irradiation (i.e. an electromagnetic radiation) of animal serum preparations and other blood-derived products (see Title, Abstract, and sections “Ionizing Radiation” and “Gamma Irradiation”, for instances), disclose the fact that gamma irradiation is regularly employed in order to mitigate the risk of various adventitious agents, along with regular serum testing or screenings for such adventitious agents, including testing for sterility, mycoplasma, and various other specific viruses; wherein the batches or lots of serum can be made up of serum pooled from many donor subjects or animals (see entire section “Serum Testing for Adventitious Agents” on p. 7); wherein they disclose various treatment methods that can be employed in order to further mitigate the risk of adventitious agents that might be present at levels which are less than the limits of detection of current analytic methods, including micropore filtration, ultraviolet (UV) irradiation, heat treatment, chemical treatments, as well as ionizing radiations including electron beam radiations, X-irradiation, and gamma irradiation (see entire disclosure on page 8-9; sections “Ionizing Radiation” and “Gamma Irradiation”); and wherein they disclose the benefits of gamma irradiation stating that “One reason why the gamma irradiation method has been commonly used for pathogen reduction in serum is that it may be performed on serum in the original product containers. Also, when done at extremely low temperatures, the performance capabilities of the serum are relatively unaffected. Cold chain management is essential during the steps leading up to and following irradiation so that the essential characteristics of serum will remain intact” (see section “Gamma Irradiation” on page 9).
Park et al (2017), while comparing the efficacy of sodium hyaluronate with cyclosporin ophthalmic solution for treatment of dry eye, disclose the fact that sodium hyaluronate can be used as a safe and effective substitute for cyclosporin as a component in artificial tears (see Abstract, Introduction, and Conclusions), and that the commonly used doses of sodium hyaluronate are well tolerated by patients, which makes them potentially useful treatment options for dry eye in clinical practice. Park et al also disclose that sodium hyaluronate is a “glycosaminoglycan with a viscoelastic rheology and a natural component of the tear film” (see Introduction, 3rd paragraph). Additionally, hyaluronic acid is known in the art to be a natural component in circulation and serum, as well as a known natural component of the tear film (as evidenced by the disclosure from Isman et al, 2007; see Abstract and Introduction on pages 346-347, Figure 1, and Table 2, for instance). Although, Park et al do not disclose the use of serum-based eye drops for treatment of dry eye conditions, they nevertheless disclose the fact that both cyclosporin and sodium hyaluronate are well known for their benefits, and are used in the art as components of artificial tears for use in treatment of ocular disorders such as dry eye conditions in patients in need thereof.
Thus, given the detailed teachings from Park et al when taken with the disclosure from Nakamura et al and Versteegen et al, it would have been obvious to combine effective additives (such as cyclosporin or hyaluronic acid, or salts thereof; as taught by Park et al, above) in the process of making serum-based eye drops that can be sterilized using suitable radiation sterilization methods (such as beta-rays/ a form of corpuscular radiation, gamma irradiation, or e-beam radiation; i.e. sterilizing electromagnetic radiations, as taught by Versteegen et al, above) that have already been shown in the art to effectively reduce burden of adventitious agents including infectious viruses, and various dangerous pathogens in blood-related products including samples of donor blood, especially that are to be used as pharmaceutical preparations including topical ophthalmic formulations/solutions, as already disclosed by Nakamura et al. Since, Chiang et al already disclose that the blood samples from which serum was prepared were already typed and screened using blood bank standard screening (that includes serotyping and virus screenings), an artisan of ordinary skill in the art would have fully contemplated such testing/screening, and pooling of serum samples from plurality of donors (including allogeneic donors), viral inactivation using sterilization with suitable electromagnetic radiations such as gamma irradiation (or corpuscular radiation as per need) at one or more desired steps for effective reduction in levels of biological contaminants, pathogens, and/or variety of dangerous viruses, etc., as well as incorporation of additives (known to be used for same ophthalmic purposes). It is noted that hyaluronic acid (a natural component of tear film) or salt thereof being a polymeric component of the eye drop formulation would intrinsically determine the viscosity of the eye drops, once incorporated at suitable levels. Additionally, since hyaluronic acid is known to be a natural component in circulation and serum (as evidenced by the disclosure from Isman et al, 2007; see Abstract and Introduction on pages 346-347, Figure 1, and Table 2, for instance), as well as a known natural component of the tear film, addition of such additives for supplementation in the pooled serum in order to make effective eye drop formulations would have been obvious to a person of ordinary skill in the art given the benefits it provides in terms of its viscoelastic properties, especially for dry eye conditions as already taught and/or suggested by Park et al, as discussed above.
Therefore, the claimed process as generically presented fails to distinguish itself over the combined teachings and/or suggestions from the cited prior art references as discussed above.
2. Claims 10, 17, 18 and 23 (as currently amended) are rejected under 35 U.S.C. 103 as being unpatentable over Chiang et al (2009; previously cited by examiner) taken with Nakamura et al (2003; NPL cited as ref. [U] on PTO 892 form), Versteegen et al (2016; NPL cited as ref. [V] on PTO 892 form), and [Park et al (2017; previously cited by examiner), as evidenced by Isman et al (2007, previously cited as pertinent prior art)] as applied to claims 1-3, 5-8, 11, 12, 14-16, 19, 21 and 22 above, and further in view of Friedman (WIPO 2018; FOR previously cited by examiner) and Semeraro et al (2014; NPL previously cited by examiner),.
Claim 10 is directed to “The method of claim 1, further comprising after applying radiation to the pool of serum, adding stabilizers to the serum that allow the eye drops to be stably stored at approximately 70 degrees Fahrenheit.”
Claim 17 is directed to “The method of claim 15, wherein the packaging includes single dose containers.”
Claim 18 is directed to “The method of claim 1, further comprising combining the eye drops with a medium that dissolves in an eye over time and releases the eye drops in a controlled and time-dependent manner.”
Claim 23 (as currently amended) is directed to “The method of claim 1, further comprising, after applying radiation to the pool of serum, adding a cannabinoid to the serum.”
The detailed teachings and/or suggestions from the cited prior art references of Chiang et al taken with Nakamura et al, Versteegen et al, and Park et al (as evidenced by Isman et al), as they pertain to pending claims 1-3, 5-8, 11, 12, 14-16, 19, 21 and 22 have been discussed above, and are further relied upon in the same manner hereinafter.
However, the method to produce eye drops as recited in claim 1, further comprising, adding one or more stabilizers, or adding a medium for controlled release, or packaging in a single dose container, or adding a cannabinoid” (see instant claims 10, 18 and 23), have not been specifically disclosed and/or exemplified by the teachings of the cited prior art references, as discussed above.
It is to be noted that applicant’s disclosure (see page 11, [0044]) states the following;
PNG
media_image1.png
147
675
media_image1.png
Greyscale
Friedman (WIPO, 2018) disclose synergistic compositions comprising sulfated polysaccharides in combination with one or more anti-inflammatory agents including cannabinoids (see Abstract, Summary of the invention, and claims 1, 5 and 10, for instances) for treating inflammatory conditions associated with, for example, conjunctivitis, commonly known as “red eye” or “pink eye”, one of the most frequent ocular disorders observed in ophthalmic emergency departments (see page 1, last paragraph; page 5, 3rd paragraph, for instances); wherein the compositions can be in various types of dosage forms including single dose or multiple dose, for instance liquid, semi-solid or solid dosage forms including topical or mucosal delivery systems, and wherein the topical delivery system may be in form of eye drops (see page 13, section “The vehicle forms”, in particular), and can be formulated in suitable controlled/sustained or delayed release forms with appropriate stabilizers and/or other required excipients, which are well known in the art of such formulations.
Semeraro et al (2014), while evaluating the efficacy of 50% autologous serum eye drops in different ocular surface pathologies (see title, and Summary on page 1), disclose the production method for autologous serum eye drops, wherein the final eye drop product was packaged in single-dose eye drops, wherein “single application packs were packed in bags of 20 and marked with label plate” for further validation and use in patients (see page section “Materials and methods”, page 3, left column, second to last paragraph).
Thus, given the beneficial teachings for including anti-inflammatory cannabinoids in compositions in various suitable dosage forms that are useful in treating inflammatory ocular disorders, in particular in the form of eye drops formulations (see teachings of Friedman, above), it would have been obvious to an artisan of ordinary skill in the art to successfully incorporate and/or further combine suitable excipients, stabilizers, and/or additives, including anti-inflammatory agents such as a cannabinoid, and for stabilizing the dosage forms for storage and desired release properties, as well as for the known benefits of incorporating natural plant-based anti-inflammatory agent in the serum-based eye drop formulations as already disclosed by the combined teachings and/or suggestions from the cited prior art references of Chiang et al when taken with Nakamura et al, Versteegen et al, and Park et al, unless evidence/data provided on record to the contrary (which is currently lacking on record; see instant specification, pages 11-13, [0044]-[0050], for instance). Since, instant claims do not require any specific stabilizer added to the irradiated pool of serum, and/or any specific component or configuration(s) for the controlled release formulation per se, the disclosure of Friedman pertaining to the vehicle forms in particular for topical delivery systems and suitable dosage forms, would have been obvious to a person of ordinary skill in the art, and would have been fully contemplated by an artisan making such serum-based eye drop formulations as currently claimed. Moreover, given the specific teachings from Semeraro et al (for packaging eye drop formulations in single dose containers as discussed above), such packaging and storage of manufactured serum-based eye drops would have been obvious to an artisan in the art, depending on the need, as specifically disclosed and/or suggested by Semeraro et al when taken with the combined disclosure form Friedman for various dosage forms, stabilizers, and/or excipients, as discussed above. Unless evidence and/or data provided on record to the contrary, such method steps for packaging and storage of prepared serum-based eye drop formulations would have been obvious and fully contemplated, as per need in the art, by an artisan of ordinary skill given the combined disclosure from the cited prior art references of Chiang et al taken with Nakamura et al, Versteegen et al, and Park et al (as evidenced by Isman et al), and further in view of Friedman and Semeraro et al, as discussed above.
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Examiner’s Response to Applicant’s Arguments
Applicant’s arguments filed on 03/03/2026 (see Pre-appeal brief conference request remarks) with respect to pending claim(s) of record have been considered but are moot in view of the new grounds of objections/rejections made in this office action, as discussed above.
Conclusion
NO claims are currently allowed.
Pertinent Prior Art:
1. Isman et al (2007; NPL cited previously by examiner)- “Evaluation of serum hyaluronic acid level and hyaluronidase activity in acute and chronic hepatitis C”, The Journal of International Medical Research, 2007, vol. 35, pages 346-352 (disclose the fact that hyaluronic acid is a natural constituent of blood serum in normal individuals, and its levels are known in the art to be elevated during disease progression and major tissue injury- such as marker for liver damage; see Abstract and Introduction on pages 346-347, Figure 1, and Table 2, for instance).
2. Tuck et al (2009; previously cited by examiner)- “Standard Operating Procedures for Serum and Plasma Collection: Early Detection Research Network Consensus Statement Standard Operating Procedure Integration Working Group”, J. Proteome Res., 2009 January, vol. 8(1), pages 113–117; doi:10.1021/pr800545q (disclose clinical SOP for routine collection of blood samples and preparation of serum using the implied but essential step of blood coagulation and centrifugation in order to remove cells and other clotting factors after clotting; see Abstract, and page 3, entire section “Serum Handling Considerations”, for instance)
3. CDC: Blood safety basics (2011; previously cited by examiner)- Published online on 08/23/2011 at the website - https://www.cdc.gov/bloodsafety/basics.html (total pages 2) (year: 2011). Discloses standard blood bank screening or testing protocol for donated blood that includes blood type analyses as well as screening pathogenic viruses including HIV, hepatitis B, C, etc.
4. Tseng et al (2016; previously cited by examiner)- “Synergic effect of artificial tears containing epigallocatechin gallate and hyaluronic acid for the treatment of rabbits with dry eye syndrome”, PLoS ONE 11(6): e0157982. doi:10.1371/journal.pone.0157982 (total pages 18). Tseng et al disclose that artificial tears formulations containing epigallocatechin gallate in combination with hyaluronic acid (HA) showed significant anti-inflammatory and mucoadhesive properties when used as topical eye drops, and were effective in treating dry eye syndrome (DES) in treated animals (see Abstract, Discussion on page 16, last paragraph).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
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, LOUISE W HUMPHREY can be reached at 571-272-5543. 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.
SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
Prosecution Insights